A Phase 3 interventional study of TAK-755 and Standard of care in Thrombotic Thrombocytopenic Purpura (TTP), sponsored by Baxalta now part of Shire. Completed at 33 sites in 9 countries. Open to participants aged 0 Years to 70 Years. Per ClinicalTrials.gov, last updated 2026-02-09.
Sponsored by Baxalta now part of Shire · Phase 3, Interventional, and Prevention
Thrombotic thrombocytopenic purpura (or TTP for short) is a condition where blood clots form in small blood vessels throughout the body. The clots can limit or block the flow of oxygen-rich blood to the body's organs, such as the brain, kidneys, and heart. As a result, serious health problems can develop. The increased clotting that occurs in TTP uses up the cells that help the blood to clot, called platelets. With fewer platelets available in the blood, bleeding problems can occur. People who have TTP may bleed underneath the skin forming purple bruises or purpura, or from the surface of the skin. TTP also can cause anemia, a condition in which red blood cells break apart faster than the body can replace them leading to lower than normal number of red blood cells.
A lack of activity in the ADAMTS13 enzyme, a protein in the blood involved in blood clotting, causes TTP. The enzyme breaks up another blood protein called von Willebrand factor that clumps together with platelets to form blood clots. Some people are born with this condition, others get the condition during their life. Many people who born with TTP experience frequent flareups that need to be treated right away. If not treated It can be fatal or cause lasting damage, such as brain damage or a stroke. BAX 930 is a medicine that replaces ADAMTS13 and can prevent or control TTP flareups, called TTP events.
The main aim of this study is to compare the number of TTP events in people born with severe TTP when they treated with BAX 930 versus when they are treated with the standard treatment. Treatment will be given in 2 ways:
Both BAX 930 and standard treatment are given slowly through a vein (infusion).
At the first visit, the study doctor will check if you can participate in the study. If you are eligible and enter the study, you will follow an assigned schedule and either start with BAX 930 (Period 1) and then switch to standard treatment (Period 2) or start with standard treatment (Period 1) and then switch to BAX 930 (Period 2). Everyone will be treated with BAX 930 again for Period 3. Each Period will last approximately 6 months.
If you enter the study to control an acute TTP event, you will follow a schedule receiving either BAX 930 or standard care to treat your acute TTP event. Once the acute TTP event has gotten better, you can decide to continue in the study and be given treatment to prevent TTP events from happening, following the schedule above.
Another study's aim is to assess side effects from treatment with BAX 930 and standard treatment. To do that, the study doctor will ask you questions about your health at each study visit.
The study doctors will also check how long BAX 930 stays in the blood of the participants, over time. They will do this from blood samples taken after participants receive their specific infusions of BAX 930. This will happen at different times during the study.
1 month after all treatment has been completed, participants will visit the clinic for a final check-up.
Participant has a documented diagnosis of severe hereditary ADAMTS13 deficiency, defined as:
Note: Participants currently receiving prophylactic therapy will be screened immediately prior to their usual prophylactic infusion
Exclusion Criteria:
Participant has been diagnosed with hepatic dysfunction, as evidenced by, but not limited to, any of the following:
Participants received a single intravenous (IV) infusion of 40 international units per kilogram (IU/kg) rADAMTS13 manufactured in Orth, Austria (TAK-755 ORT), every 2 weeks (Q2W) for 6 months in Period 1 followed by standard of care (SoC) for 6 months in Period 2. Thereafter participants received rADAMTS13 manufactured in Singapore (TAK-755 SIN), dose IV infusion of 40 IU/kg Q2W for 6 months in Period 3. TAK-755 ORT could be replaced with TAK-755 SIN and vice versa depending on availability and other criteria.
Biological: TAK-755 · Biological: Standard of care
Participants received SoC for 6 months in Period 1 followed by IV infusions of 40 IU/kg dose of TAK-755 ORT Q2W in Period 2 for the next 6 months. Thereafter participants received TAK-755 SIN dose IV infusions of 40 IU/kg Q2W for another 6 months in Period 3. TAK-755 ORT could be replaced with TAK-755 SIN and vice versa depending on availability and other criteria.
Biological: TAK-755 · Biological: Standard of care
Participants experiencing an acute TTP event who met all other inclusion criteria and entered the study through the TAK-755 cohort of the Urgent Treatment Period received initial dose of IV infusion 40 IU/kg \[+/- 4 IU/kg\] TAK-755 ORT or TAK-755 SIN on Day 1 followed by a subsequent dose IV infusions of 20 IU/kg \[+/- 2 IU/kg\] TAK-755 ORT or TAK-755 SIN on Day 2 and an additional daily dose IV infusions of 15 IU/kg \[+/- 1.5 IU/kg\] TAK-755 on Day 3 until 2 days after the acute event was resolved. Upon resolution of the acute TTP event, participants had the option to either move to the prophylaxis cohort of the study or discontinue entirely.
Biological: TAK-755
Participants experiencing an acute TTP event who met all other inclusion criteria and entered the study through the SoC cohort of the Urgent Treatment Period received the investigator-recommended SoC and dosing regimen until the acute event was resolved. Upon resolution of the acute TTP event, participants had the option to either move to the prophylaxis cohort of the study or discontinue entirely.
Biological: Standard of care
Participants in prophylaxis cohort will receive IV infusions of 40 IU/kg TAK-755 ORT during Period 1 and Period 2 and switch to TAK-755 SIN during Period 3 for six months once in a week or twice in a week. In On-demand cohort participants will receive daily IV dose of TAK-755.
Also known as: rADAMTS13, SHP-655, recombinant ADAMTS13, BAX 930
Participants will receive Investigator-recommended Standard of care (SoC).
Number of Participants With Acute Thrombotic Thrombocytopenic Purpura (TTP) Events During Prophylactic Treatment
As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.
Time frame: Up to 74.5 months
Percentage of Acute Thrombotic Thrombocytopenic Purpura (TTP) Events Responding to TAK-755
Percentage of acute TTP events responding to TAK-755, was defined as not requiring the use of another human disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13 (ADAMTS13)-containing agent. As per planned analysis, data for this outcome measure were collected and reported only for the TAK-755 treatment arm of both the prophylaxis (irrespective of the prophylaxis periods) and on demand cohorts.
Time frame: Up to 79.6 months
Time to Resolution of Acute TTP Events
Time to resolution of acute TTP events following initiation of treatment with TAK-755 or SoC agent was assessed. Acute TPP events were considered resolved when: (a) Platelet count was \>150,000 per microliter (μL) or drop of platelet count was within 25 percent (%) of baseline, whichever occurred first, and (b) Elevation of lactate dehydrogenase (LDH) \<1.5 x baseline or \<1.5 x upper limit of normal (ULN). As per planned analysis, data for this outcome measure were collected and reported in a combined manner irrespective of the prophylaxis treatment Periods, partitioned per treatment received (TAK-755 and SoC) for the on demand and prophylactic cohorts.
Time frame: Up to 79.6 months
Number of Participants With Thrombocytopenia During Prophylactic Treatment
Thrombocytopenia was defined as a decrease in platelet count ≥25 % of baseline or a platelet count \<150,000/μL, reported by treatment arm for the prophylactic cohort. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.
Time frame: Up to 79.6 months
Number of Participants With Microangiopathic Hemolytic Anemia During Prophylactic Treatment
Microangiopathic hemolytic anemia was defined as an elevation of LDH \>1.5\* of baseline or \>1.5\*ULN (with a possible evidence of schistocytes on blood smear) and was reported by treatment arm for the prophylactic cohort. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.
Time frame: Up to 79.6 months
Number of Participants With Neurological Symptoms During Prophylactic Treatment
Neurological symptoms (TTP related) (e.g., confusion, dysphonia, dysarthria, focal or general motor symptoms including seizures), were reported by treatment arm for the prophylactic cohort. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.
Time frame: Up to 79.6 months
Number of Participants With Renal Dysfunction During Prophylactic Treatment
Renal dysfunction was defined as an increase in serum creatinine \>1.5\*baseline. Number of participants with renal dysfunction were reported by treatment arm for the prophylactic cohort. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.
Time frame: Up to 79.6 months
Number of Participants With Abdominal Pain During Prophylactic Treatment
Number of participants with abdominal pain (TTP related) were reported by treatment arm for the prophylaxis cohort. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.
Time frame: Up to 79.6 months
Number of Supplemental Doses Prompted by Subacute TTP Event During Prophylactic Treatment
Number of supplemental doses prompted by subacute TTP events were reported by treatment for the prophylactic cohort. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.
Time frame: Up to 79.6 months
Number of Participants With Dose Modification Not Prompted by an Acute TTP Event During Prophylactic Treatment
Number of participants with dose modification not prompted by an acute TTP event were reported by treatment for the prophylactic cohort. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.
Time frame: Up to 79.6 months
Number of Participants With Acute TTP Events on Their Final Dose
Number of participants with acute TTP events on their final dose and dosing regimen for the prophylactic cohort were reported. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.
Time frame: Up to 79.6 months
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Treatment Emergent Adverse Events (Serious TEAEs)
AE: Any untoward medical occurrence in participants administered IP that does not necessarily have a causal relationship with treatment. TEAE: AE that has start date-time on/after start date-time of first dose of treatment participant is taking on that assessment/period or if it has start date-time before start date-time of first dose but increases in severity on/after start date-time of the first dose of treatment. SAE: An untoward medical occurrence that at any dose meets 1 or more of following criteria: death; initial/prolonged in-patient hospitalization; life threatening experience; persistent/significant disability/incapacity; congenital anomaly, medically important event (may not be immediately life threatening or result in death or require hospitalization but may require medical or surgical intervention to prevent 1 of the other outcomes). Vital signs, clinical chemistry, hematology as assessed by the investigator were reported as AE.
Time frame: Up to 79.6 months
Number of Participants With Inhibitory Antibodies to ADAMTS13
Number of participants with inhibitory antibodies to ADAMTS13 were reported. As per planned analysis, data for this outcome measure were collected and reported in a combined manner irrespective of the Prophylaxis Periods and partitioned as per the treatment received during the course of the study, presented for the prophylaxis cohorts only.
Time frame: Up to 79.6 months
Total Quantity of ADAMTS13 Administered During the Treatment of Acute TTP Events in Participants in TAK-755 Treatment Arm
Total quantity of ADAMTS13 administered during the treatment of acute TTP events (all acute TTP events irrespective of central lab confirmation were included) was assessed. Acute TTP events typically require 3 to 4 days of intensified treatment. As per planned analysis, data for this outcome measure were collected and reported only for the TAK-755 treatment arm of both the prophylaxis (irrespective of the prophylaxis periods) and on demand cohorts.
Time frame: Up to 79.6 months
Incremental Recovery (IR) of ADAMTS13 Activity for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment
ADAMTS13 activity was measured by the fluorescent resonance energy transfer (FRETS) assay. IR was defined as body weight normalized maximum increase in plasma ADAMTS13 activity level. IR of ADAMTS13 activity for SoC agent and TAK-755 in plasma was assessed. (IU/mL)/(IU/kg) stands for (International units per milliliter)/(International units per kilogram). PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1, end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
Time frame: PK-I (Month 1:Day 1 up to 12), PK-II (Month 12:Day 1 up to 12), and PK-III (Month 19:Day 1 up to 12): Pre-infusion and at multiple timepoints post-infusion up to 288 hours
IR of ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment
ADAMTS13 antigen was measured using a commercial ADAMTS13 enzyme-linked immunosorbent assay (ELISA) employing ADAMTS13 antigen. IR was defined as body weight normalized maximum increase in plasma ADAMTS13 antigen. IR of ADAMTS13 antigen for SoC agent and TAK-755 in plasma was assessed. (µg/mL)/ (µg/kg) stands for (microgram per milliliter)/(microgram per kilogram). PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1, end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
Time frame: PK-I (Month 1:Day 1 up to 12), PK-II (Month 12:Day 1 up to 12), and PK-III (Month 19:Day 1 up to 12): Pre-infusion and at multiple timepoints post-infusion up to 288 hours
Area Under the Plasma Curve [AUC]All of ADAMTS13 Activity for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment
h\*IU/mL denotes for hours\*international units per milliliters. PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
Time frame: PK-I (Month 1:Day 1 up to 12), PK-II (Month 12:Day 1 up to 12), and PK-III (Month 19:Day 1 up to 12): Pre-infusion and at multiple timepoints post-infusion up to 288 hours
AUCall of ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment
h\*µg/mL denotes for hours\*microgram per milliliters. PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
Time frame: PK-I (Month 1:Day 1 up to 12), PK-II (Month 12:Day 1 up to 12), and PK-III (Month 19:Day 1 up to 12): Pre-infusion and at multiple timepoints post-infusion up to 288 hours
Terminal Half-Life (t1/2) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment
PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
Time frame: PK-I (Month 1:Day 1 up to 12), PK-II (Month 12:Day 1 up to 12), and PK-III (Month 19:Day 1 up to 12): Pre-infusion and at multiple timepoints post-infusion up to 288 hours
Mean Residence Time Extrapolated to Infinity (MRT0-inf) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment
PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
Time frame: PK-I (Month 1:Day 1 up to 12), PK-II (Month 12:Day 1 up to 12), and PK-III (Month 19:Day 1 up to 12): Pre-infusion and at multiple timepoints post-infusion up to 288 hours
Clearance (CL) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment
PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
Time frame: PK-I (Month 1:Day 1 up to 12), PK-II (Month 12:Day 1 up to 12), and PK-III (Month 19:Day 1 up to 12): Pre-infusion and at multiple timepoints post-infusion up to 288 hours
Volume at Steady State (Vss) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment
PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
Time frame: PK-I (Month 1:Day 1 up to 12), PK-II (Month 12:Day 1 up to 12), and PK-III (Month 19:Day 1 up to 12): Pre-infusion and at multiple timepoints post-infusion up to 288 hours
Maximum Concentration (Cmax) of ADAMTS13 Activity for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment
IU/mL stands for International units per milliliter. PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth,Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
Time frame: PK-I (Month 1:Day 1 up to 12), PK-II (Month 12:Day 1 up to 12), and PK-III (Month 19:Day 1 up to 12): Pre-infusion and at multiple timepoints post-infusion up to 288 hours
Cmax of ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment
µg/mL stands for microgram per milliliter. PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
Time frame: PK-I (Month 1:Day 1 up to 12), PK-II (Month 12:Day 1 up to 12), and PK-III (Month 19:Day 1 up to 12): Pre-infusion and at multiple timepoints post-infusion up to 288 hours
Change From Baseline in Assessment of Von Willebrand Factor:Antigen (VWF:Ag) During Prophylactic Treatment
VWF:Ag is a measure of total VWF protein and was assessed using a sandwich ELISA employing polyclonal anti-human-VWF antibodies. Assessments of VWF:Ag at baseline and following infusion of the SoC agent and TAK-755 treatment during the initial PK assessment were reported. PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
Time frame: PK-I (Month 1:Day 12), PK-II (Month 12:Day 12), and PK-III (Month 19:Day 12): Post-infusion at 288 hours
Change From Baseline in Assessment of Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) During Prophylactic Treatment
VWF:RCo provides a measure of the ability of VWF to bind platelet glycoprotein Ib. Stabilized platelets are agglutinated in the presence of VWF and the antibiotic Ristocetin. Assessments of VWF:RCo at baseline and following infusion of the SoC agent and TAK-755 treatment during the initial PK assessment was reported. PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
Time frame: PK-I (Month 1:Day 12), PK-II (Month 12:Day 12), and PK-III (Month 19:Day 12): Post-infusion at 288 hours
Assessment of ADAMTS13 Activity Expressed as Pre-Infusion ADAMTS13 Levels
PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
Time frame: PK-I (Month 1:Day 1), PK-II (Month 12:Day 1), and PK-III (Month 19:Day 1): Pre-infusion (within 1 hour)
Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:RCo
PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
Time frame: PK-I (Month 1:Day 1), PK-II (Month 12:Day 1), and PK-III (Month 19:Day 1): Pre-infusion (within 1 hour)
Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:Ag
PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
Time frame: PK-I (Month 1:Day 1), PK-II (Month 12:Day 1), and PK-III (Month 19:Day 1): Pre-infusion (within 1 hour)
Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:mm Low Resolution (Res.) Intermediate
PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
Time frame: PK-I (Month 1:Day 1), PK-II (Month 12:Day 1), and PK-III (Month 19:Day 1): Pre-infusion (within 1 hour)
Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:mm Low Res. Large
PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
Time frame: PK-I (Month 1:Day 1), PK-II (Month 12:Day 1), and PK-III (Month 19:Day 1): Pre-infusion (within 1 hour)
Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:mm Low Res. Small
PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
Time frame: PK-I (Month 1:Day 1), PK-II (Month 12:Day 1), and PK-III (Month 19:Day 1): Pre-infusion (within 1 hour)
Number of Participants With Total Binding Antibodies to ADAMTS13 During Prophylactic Treatment
Total binding antibodies to ADAMTS13 were measured by an ELISA-based assay, detecting total immunoglobulins (IgG, IgA, and IgM). As per planned analysis, data for this outcome measure were collected and reported per sequence (Prophylaxis Cohort I: TAK-755 Then SoC and Prophylaxis Cohort II: SoC Then TAK-755) for the prophylaxis cohorts only.
Time frame: Up to 79.6 months
Number of Participants With Neutralizing Antibodies to ADAMTS13 During Prophylactic Treatment
Neutralizing antibodies were measured by a Bethesda method with Nijmegen modification using the ADAMTS13 FRETS-VWF73 activity assay. As per planned analysis, data for this outcome measure were collected and reported per sequence (Prophylaxis Cohort I: TAK-755 Then SoC and Prophylaxis Cohort II: SoC Then TAK-755) for the prophylaxis cohorts only.
Time frame: Up to 79.6 months
Number of Participants With Anti-Chinese Hamster Ovary (Anti-CHO) Protein Antibodies During Prophylactic Treatment
Total immunoglobulin antibodies (Immunoglobulin G \[IgG\], A \[IgA\], and M \[IgM\]) against CHO protein were analyzed using ELISA assay. As per planned analysis, data for this outcome measure were collected and reported per sequence (Prophylaxis Cohort I: TAK-755 Then SoC and Prophylaxis Cohort II: SoC Then TAK-755) for the prophylaxis cohorts only.
Time frame: Up to 79.6 months
Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in cTTP-Patient Experience Questionnaire (cTTP-PEQ) Total Score
The cTTP-PEQ consists of 26 questions designed to assess the participant's experience of fatigue, joint, muscle, abdominal \&chest pain in the previous 24 hours, neurologic manifestations, bruising, feelings of depression and mood alterations, and activity limitation in the past 7 days, and participant's attitudes, experienced side effects, work/school absences and travel impact associated with treatment received for TTP during the previous 2 weeks. The cTTP PEQ is focused on measuring the symptoms and impacts of disease. The total scores range from 0 to 162. A higher score indicates greater burden and poor quality of life. As per planned analysis,for the prophylaxis cohorts the data for this outcome measure were collected and reported by categorizing as per Prophylaxis Periods and per age groups,≥12 years,12 to 18 years,≥18 years for both on demand(OD) and prophylaxis cohorts. No participants in the OD Cohorts had cTTP-PEQ data available for analysis at scheduled post-baseline visits.
Time frame: Baseline, Urgent Treatment Period: Day 7, End of Period 1 (Month 6), End of Period 2 (Month 12), and End of Period 3 (Month 19)
Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Physical and Mental Component Scores of the 36-Item Short Form Health Survey Version 2 (SF-36v2)
SF-36v2 is questionnaire that evaluated participant's health related quality of life. It included 36 questions related to 8 health dimensions: physical functioning, role-physical(role limitations due to physical health problems), bodily pain, general health, vitality(energy/fatigue),social functioning, role-emotional(role limitations due to emotional problems),\& mental health. Based on these 4 scales(physical functioning, role-physical, bodily pain, general health), physical component score was generated which ranges between 0 \&100, with higher scores indicating a better quality of life. Based on these 4 scales(vitality, social functioning, role-emotional,\&mental health), mental component score was generated ranging between 0\&100, with higher scores=better quality of life. As per planned analysis, for the prophylaxis cohorts data for this outcome measure were collected\&reported by categorizing as per Prophylaxis Periods and per component scores for both on demand\&prophylaxis cohorts.
Time frame: Baseline, Urgent Treatment Period: Day 7, End of Period 1 (Month 6), End of Period 2 (Month 12), and End of Period 3 (Month 19)
Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Abbreviated 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) Domain Scores
TSQM is a treatment satisfaction measure used to assess the overall level of participant's satisfaction or dissatisfaction with their medications. TSQM-9 is a 9-item, validated, self-administered instrument used to assess participant's satisfaction with medication. The three domains assessed are treatment effectiveness, convenience, and global satisfaction. The score of each of the 3 domains is based on an algorithm to create a score of 0 to 100. Higher score indicates greater satisfaction in that domain. As per planned analysis, for the prophylaxis cohorts data for this outcome measure were collected and reported by categorizing as per Prophylaxis Periods and per domain scores for both on demand and prophylaxis cohorts.
Time frame: Baseline, Urgent Treatment Period: Day 7, End of Period 1 (Month 6), End of Period 2 (Month 12), and End of Period 3 (Month 19)
Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EuroQoL 5 Dimensions Questionnaire 3-Level (EQ-5D-3L) Domain Scores
EQ-5D-3L health questionnaire is a participant-answered questionnaire scoring 5 dimensions(domains) - mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is scored on an ordinal scale with 3 available levels of response and scores ranging from 1 to 3, "no problems," "some problems," and "extreme problems," respectively. Lower scores for the domains in the EQ-5D-3L indicate improvement. As per planned analysis, for the prophylaxis cohorts data for this outcome measure were collected and reported by categorizing as per Prophylaxis Periods and per domain scores for both on demand and prophylaxis cohorts.
Time frame: Baseline, Urgent Treatment Period: Day 7, End of Period 1 (Month 6), End of Period 2 (Month 12), and End of Period 3 (Month 19)
Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EQ-5D-youth (EQ-5D-Y) Domain Scores
EQ-5D-Y health questionnaire is a participant answered questionnaire scoring 5 dimensions (domains) - mobility, self-care, usual activities, pain/discomfort and anxiety/depression assessed in participants aged from 8 to 16 years. The EQ-5D-Y descriptive system includes 5 descriptive items: Mobility, self-care, doing usual activities, having pain or discomfort, and feeling anxiety or depressed. Each dimension is scored at 3 levels: 1=No problems, 2=some problems, and 3=a lot of problems. Lower scores for the domains in the EQ-5D-Y indicate improvement. As per planned analysis, for the prophylaxis cohorts data for this outcome measure were collected and reported by categorizing as per Prophylaxis Periods and per domain scores for both on demand and prophylaxis cohorts.
Time frame: Baseline, Urgent Treatment Period: Day 7, End of Period 1 (Month 6), End of Period 2 (Month 12), and End of Period 3 (Month 19)
Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Pediatric Quality of Life Inventory (Peds QL) Scale Total Scores
The PedsQL is a generic health related quality of life instrument designed specifically for a pediatric population and captures following domains: physical functioning, emotional functioning, social functioning, school functioning, psychosocial summary, physical health and total score. The Peds-QL total score consists of all 23 items of all domains. This modular instrument uses a 5-point scale: from 0 (never) to 4 (almost always). Items are reversed scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. Higher scores indicate better quality of life. As per planned analysis, for the prophylaxis cohorts data for this outcome measure were collected and reported by categorizing as per Prophylaxis Periods and per age groups, 2 to \< 5 years, 5 to \< 8 years, 8 to \< 13 years, and 13 to \< 18 years, for both on demand and prophylaxis cohorts.
Time frame: Baseline, Urgent Treatment Period: Day 7, End of Period 1 (Month 6), End of Period 2 (Month 12), and End of Period 3 (Month 19)
Resource Utilization: Annualized Length of Hospital Stay for Acute TTP Events for Prophylaxis Cohorts
The annualized number of days participants stayed in hospital for acute TTP events were assessed. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts in a combined manner for Periods 1 and 2 for SoC treatment and for Periods 1, 2, and 3 for TAK-755 treatment respectively.
Time frame: Up to 79.6 months
Resource Utilization: Annualized Number of Acute Care Visits for Prophylaxis Cohorts
Annualized number of acute care visits was calculated as the number of acute care visits × 365.25/(End date - treatment start date + 1). As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts in a combined manner for Periods 1 and 2 for SoC treatment and for Periods 1, 2, and 3 for TAK-755 treatment respectively.
Time frame: Up to 79.6 months
Resource Utilization: Annualized Number of Days Missed From School or Work for Prophylaxis Cohorts
Annualized number of days missed from school or work were assessed. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts in a combined manner for Periods 1 and 2 for SoC treatment and for Periods 1, 2, and 3 for TAK-755 treatment respectively.
Time frame: Up to 79.6 months
Participants took part in the study at various investigative sites globally from 13 October 2017 to 30 May 2024.
| Milestone | Prophylaxis Cohort I: TAK-755 Then SoC | Prophylaxis Cohort II: SoC Then TAK-755 | On Demand Cohort I: TAK-755 | On Demand Cohort II: SoC |
|---|---|---|---|---|
| Started | 0 | 0 | 2 | 4 |
| Safety analysis set | 0 | 0 | 2 | 4 |
| Full analysis set | 0 | 0 | 2 | 4 |
| Modified full analysis set | 0 | 0 | 2 | 4 |
| Completed | 0 | 0 | 2 | 3 |
| Not completed | 0 | 0 | 0 | 1 |
| Withdrew: Physician decision | 0 | 0 | 0 | 1 |
| Milestone | Prophylaxis Cohort I: TAK-755 Then SoC | Prophylaxis Cohort II: SoC Then TAK-755 | On Demand Cohort I: TAK-755 | On Demand Cohort II: SoC |
|---|---|---|---|---|
| Started | 23 | 25 | 0 | 0 |
| Safety analysis set | 23 | 25 | 0 | 0 |
| Full analysis set | 23 | 24 | 0 | 0 |
| Modified full analysis set | 21 | 24 | 0 | 0 |
| Completed | 23 | 24 | 0 | 0 |
| Not completed | 0 | 1 | 0 | 0 |
| Withdrew: Reason not specified | 0 | 1 | 0 | 0 |
| Milestone | Prophylaxis Cohort I: TAK-755 Then SoC | Prophylaxis Cohort II: SoC Then TAK-755 | On Demand Cohort I: TAK-755 | On Demand Cohort II: SoC |
|---|---|---|---|---|
| Started | 23 | 24 | 0 | 0 |
| Completed | 23 | 23 | 0 | 0 |
| Not completed | 0 | 1 | 0 | 0 |
| Withdrew: Reason not specified | 0 | 1 | 0 | 0 |
| Milestone | Prophylaxis Cohort I: TAK-755 Then SoC | Prophylaxis Cohort II: SoC Then TAK-755 | On Demand Cohort I: TAK-755 | On Demand Cohort II: SoC |
|---|---|---|---|---|
| Started | 23 | 23 | 0 | 0 |
| Completed | 23 | 23 | 0 | 0 |
| Not completed | 0 | 0 | 0 | 0 |
As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.
| Participants | Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Prophylaxis Cohort: TAK-755 (Period 3) | Prophylaxis Cohort: SoC (Periods 1 and 2) |
|---|---|---|---|
| Number of Participants With Acute Thrombotic Thrombocytopenic Purpura (TTP) Events During Prophylactic Treatment | 0 | 0 | 1 |
Percentage of acute TTP events responding to TAK-755, was defined as not requiring the use of another human disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13 (ADAMTS13)-containing agent. As per planned analysis, data for this outcome measure were collected and reported only for the TAK-755 treatment arm of both the prophylaxis (irrespective of the prophylaxis periods) and on demand cohorts.
| percentage of events | Prophylaxis Cohort: TAK-755 | On Demand Cohort I: TAK-755 |
|---|---|---|
| Percentage of Acute Thrombotic Thrombocytopenic Purpura (TTP) Events Responding to TAK-755 | — | 100 |
Time to resolution of acute TTP events following initiation of treatment with TAK-755 or SoC agent was assessed. Acute TPP events were considered resolved when: (a) Platelet count was \>150,000 per microliter (μL) or drop of platelet count was within 25 percent (%) of baseline, whichever occurred first, and (b) Elevation of lactate dehydrogenase (LDH) \<1.5 x baseline or \<1.5 x upper limit of normal (ULN). As per planned analysis, data for this outcome measure were collected and reported in a combined manner irrespective of the prophylaxis treatment Periods, partitioned per treatment received (TAK-755 and SoC) for the on demand and prophylactic cohorts.
| days | Prophylaxis Cohort: TAK-755 | Prophylaxis Cohort: SoC | On Demand Cohort I: TAK-755 | On Demand Cohort II: SoC |
|---|---|---|---|---|
| Time to Resolution of Acute TTP Events | — | 14.8 (NA to NA) | 3.0 (NA to NA) | 1.5 (NA to NA) |
Thrombocytopenia was defined as a decrease in platelet count ≥25 % of baseline or a platelet count \<150,000/μL, reported by treatment arm for the prophylactic cohort. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.
| Participants | Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Prophylaxis Cohort: TAK-755 (Period 3) | Prophylaxis Cohort: SoC (Periods 1 and 2) |
|---|---|---|---|
| Number of Participants With Thrombocytopenia During Prophylactic Treatment | 13 | 11 | 21 |
Microangiopathic hemolytic anemia was defined as an elevation of LDH \>1.5\* of baseline or \>1.5\*ULN (with a possible evidence of schistocytes on blood smear) and was reported by treatment arm for the prophylactic cohort. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.
| Participants | Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Prophylaxis Cohort: TAK-755 (Period 3) | Prophylaxis Cohort: SoC (Periods 1 and 2) |
|---|---|---|---|
| Number of Participants With Microangiopathic Hemolytic Anemia During Prophylactic Treatment | 8 | 13 | 12 |
Neurological symptoms (TTP related) (e.g., confusion, dysphonia, dysarthria, focal or general motor symptoms including seizures), were reported by treatment arm for the prophylactic cohort. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.
| Participants | Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Prophylaxis Cohort: TAK-755 (Period 3) | Prophylaxis Cohort: SoC (Periods 1 and 2) |
|---|---|---|---|
| Number of Participants With Neurological Symptoms During Prophylactic Treatment | 4 | 9 | 7 |
Renal dysfunction was defined as an increase in serum creatinine \>1.5\*baseline. Number of participants with renal dysfunction were reported by treatment arm for the prophylactic cohort. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.
| Participants | Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Prophylaxis Cohort: TAK-755 (Period 3) | Prophylaxis Cohort: SoC (Periods 1 and 2) |
|---|---|---|---|
| Number of Participants With Renal Dysfunction During Prophylactic Treatment | 5 | 4 | 2 |
Number of participants with abdominal pain (TTP related) were reported by treatment arm for the prophylaxis cohort. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.
| Participants | Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Prophylaxis Cohort: TAK-755 (Period 3) | Prophylaxis Cohort: SoC (Periods 1 and 2) |
|---|---|---|---|
| Number of Participants With Abdominal Pain During Prophylactic Treatment | 2 | 2 | 6 |
Number of supplemental doses prompted by subacute TTP events were reported by treatment for the prophylactic cohort. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.
| supplemental doses | Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Prophylaxis Cohort: TAK-755 (Period 3) | Prophylaxis Cohort: SoC (Periods 1 and 2) |
|---|---|---|---|
| Number of Supplemental Doses Prompted by Subacute TTP Event During Prophylactic Treatment | 0 | 5 | 9 |
Number of participants with dose modification not prompted by an acute TTP event were reported by treatment for the prophylactic cohort. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.
| Participants | Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Prophylaxis Cohort: TAK-755 (Period 3) | Prophylaxis Cohort: SoC (Periods 1 and 2) |
|---|---|---|---|
| Number of Participants With Dose Modification Not Prompted by an Acute TTP Event During Prophylactic Treatment | 0 | 1 | 3 |
Number of participants with acute TTP events on their final dose and dosing regimen for the prophylactic cohort were reported. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.
| Participants | Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Prophylaxis Cohort: TAK-755 (Period 3) | Prophylaxis Cohort: SoC (Periods 1 and 2) |
|---|---|---|---|
| Number of Participants With Acute TTP Events on Their Final Dose | 0 | 0 | 1 |
AE: Any untoward medical occurrence in participants administered IP that does not necessarily have a causal relationship with treatment. TEAE: AE that has start date-time on/after start date-time of first dose of treatment participant is taking on that assessment/period or if it has start date-time before start date-time of first dose but increases in severity on/after start date-time of the first dose of treatment. SAE: An untoward medical occurrence that at any dose meets 1 or more of following criteria: death; initial/prolonged in-patient hospitalization; life threatening experience; persistent/significant disability/incapacity; congenital anomaly, medically important event (may not be immediately life threatening or result in death or require hospitalization but may require medical or surgical intervention to prevent 1 of the other outcomes). Vital signs, clinical chemistry, hematology as assessed by the investigator were reported as AE.
| Participants | Prophylaxis Cohort: TAK-755 | Prophylaxis Cohort: SoC | On Demand Cohort I: TAK-755 | On Demand Cohort II: SoC |
|---|---|---|---|---|
| TEAES | 42 | 44 | 0 | 3 |
| Serious TEAEs | 6 | 8 | 0 | 1 |
Number of participants with inhibitory antibodies to ADAMTS13 were reported. As per planned analysis, data for this outcome measure were collected and reported in a combined manner irrespective of the Prophylaxis Periods and partitioned as per the treatment received during the course of the study, presented for the prophylaxis cohorts only.
| Participants | Prophylaxis Cohort: TAK-755 | Prophylaxis Cohort: SoC |
|---|---|---|
| Number of Participants With Inhibitory Antibodies to ADAMTS13 | 1 | 0 |
Total quantity of ADAMTS13 administered during the treatment of acute TTP events (all acute TTP events irrespective of central lab confirmation were included) was assessed. Acute TTP events typically require 3 to 4 days of intensified treatment. As per planned analysis, data for this outcome measure were collected and reported only for the TAK-755 treatment arm of both the prophylaxis (irrespective of the prophylaxis periods) and on demand cohorts.
| IU | Prophylaxis Cohort: TAK-755 | On Demand Cohort I: TAK-755 |
|---|---|---|
| Total Quantity of ADAMTS13 Administered During the Treatment of Acute TTP Events in Participants in TAK-755 Treatment Arm | — | 5720.25 ± 189.858 |
ADAMTS13 activity was measured by the fluorescent resonance energy transfer (FRETS) assay. IR was defined as body weight normalized maximum increase in plasma ADAMTS13 activity level. IR of ADAMTS13 activity for SoC agent and TAK-755 in plasma was assessed. (IU/mL)/(IU/kg) stands for (International units per milliliter)/(International units per kilogram). PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1, end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
| (IU/mL)/(IU/kg) | Prophylaxis Cohort: TAK-755 ORT | Prophylaxis Cohort: TAK-755 SIN | Prophylaxis Cohort: SoC |
|---|---|---|---|
| PK-I: ADAMTS13 Activity | 0.025 ± 0.00592 | NA ± NA | 0.0212 ± 0.0267 |
| PK-II: ADAMTS13 Activity | 0.0283 ± 0.00644 | 0.0292 ± 0.00630 | — |
| PK-III: ADAMTS13 Activity | — | 0.0260 ± 0.00617 | — |
ADAMTS13 antigen was measured using a commercial ADAMTS13 enzyme-linked immunosorbent assay (ELISA) employing ADAMTS13 antigen. IR was defined as body weight normalized maximum increase in plasma ADAMTS13 antigen. IR of ADAMTS13 antigen for SoC agent and TAK-755 in plasma was assessed. (µg/mL)/ (µg/kg) stands for (microgram per milliliter)/(microgram per kilogram). PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1, end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
| (µg/mL)/ (µg/kg) | Prophylaxis Cohort: TAK-755 ORT | Prophylaxis Cohort: TAK-755 SIN | Prophylaxis Cohort: SoC |
|---|---|---|---|
| PK-I: ADAMTS13 Antigen | 0.0299 ± 0.00638 | NA ± NA | 0.0186 ± 0.00605 |
| PK-II: ADAMTS13 Antigen | 0.0339 ± 0.0080 | 0.0324 ± 0.00668 | — |
| PK-III: ADAMTS13 Antigen | — | 0.0264 ± 0.0102 | — |
h\*IU/mL denotes for hours\*international units per milliliters. PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
| h*IU/mL | Prophylaxis Cohort: TAK-755 ORT | Prophylaxis Cohort: TAK-755 SIN | Prophylaxis Cohort: SoC |
|---|---|---|---|
| PK-I: ADAMTS13 Activity | 44.15 ± 11.197 | — | 10.56 ± 8.263 |
| PK-II: ADAMTS13 Activity | 52.83 ± 11.940 | 52.98 ± 13.358 | — |
| PK-III: ADAMTS13 Activity | — | 65.65 ± 23.487 | — |
h\*µg/mL denotes for hours\*microgram per milliliters. PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
| h*µg/mL | Prophylaxis Cohort: TAK-755 ORT | Prophylaxis Cohort: TAK-755 SIN | Prophylaxis Cohort: SoC |
|---|---|---|---|
| PK-I: ADAMTS13 Antigen | 34.12 ± 9.646 | — | 7.590 ± 6.1344 |
| PK-II: ADAMTS13 Antigen | 38.79 ± 8.835 | 38.95 ± 11.137 | — |
| PK-III: ADAMTS13 Antigen | — | 49.74 ± 19.147 | — |
PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
| hours | Prophylaxis Cohort: TAK-755 ORT | Prophylaxis Cohort: TAK-755 SIN | Prophylaxis Cohort: SoC |
|---|---|---|---|
| PK-I: ADAMTS13 Activity | 47.14 ± 11.573 | — | 62.88 ± 28.927 |
| PK-I: ADAMTS13 Antigen | 53.59 ± 13.354 | — | 58.70 ± 23.575 |
| PK-II: ADAMTS13 Activity | 52.51 ± 15.579 | 45.77 ± 10.231 | — |
| PK-II: ADAMTS13 Antigen | 54.15 ± 16.553 | 49.72 ± 15.942 | — |
| PK-III: ADAMTS13 Activity | — | 35.38 ± 5.286 | — |
| PK-III: ADAMTS13 Antigen | — | 39.85 ± 3.243 | — |
PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
| hours | Prophylaxis Cohort: TAK-755-ORT | Prophylaxis Cohort: TAK-755 SIN | Prophylaxis Cohort: SoC |
|---|---|---|---|
| PK-I: ADAMTS13 Activity | 64.35 ± 17.498 | — | NA ± NA |
| PK-I: ADAMTS13 Antigen | 71.20 ± 16.538 | — | NA ± NA |
| PK-II: ADAMTS13 Activity | 65.89 ± 13.472 | 61.56 ± 11.762 | — |
| PK-II: ADAMTS13 Antigen | 72.36 ± 19.224 | 66.30 ± 18.738 | — |
| PK-III: ADAMTS13 Activity | — | 41.67 ± 6.171 | — |
| PK-III: ADAMTS13 Antigen | — | 46.30 ± 4.266 | — |
PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
| liters per hour (L/h) | Prophylaxis Cohort: TAK-755-ORT | Prophylaxis Cohort: TAK-755 SIN | Prophylaxis Cohort: SoC |
|---|---|---|---|
| PK-I: ADAMTS13 Activity | 0.0618 ± 0.0144 | — | NA ± NA |
| PK-I: ADAMTS13 Antigen | 0.0456 ± 0.0117 | — | NA ± NA |
| PK-II: ADAMTS13 Activity | 0.0530 ± 0.0134 | 0.0549 ± 0.0117 | — |
| PK-II: ADAMTS13 Antigen | 0.0409 ± 0.0109 | 0.0480 ± 0.0133 | — |
| PK-III: ADAMTS13 Activity | — | 0.0553 ± 0.0177 | — |
| PK-III: ADAMTS13 Antigen | — | 0.0462 ± 0.0110 | — |
PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
| liters | Prophylaxis Cohort: TAK-755-ORT | Prophylaxis Cohort: TAK-755 SIN | Prophylaxis Cohort: SoC |
|---|---|---|---|
| PK-I: ADAMTS13 Activity | 3.852 ± 0.916 | — | NA ± NA |
| PK-I: ADAMTS13 Antigen | 3.124 ± 0.650 | — | NA ± NA |
| PK-II: ADAMTS13 Activity | 3.401 ± 0.715 | 3.304 ± 0.635 | — |
| PK-II: ADAMTS13 Antigen | 2.812 ± 0.479 | 3.007 ± 0.613 | — |
| PK-III: ADAMTS13 Activity | — | 2.265 ± 0.669 | — |
| PK-III: ADAMTS13 Antigen | — | 2.172 ± 0.698 | — |
IU/mL stands for International units per milliliter. PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth,Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
| IU/mL | Prophylaxis Cohort: TAK-755-ORT | Prophylaxis Cohort: TAK-755 SIN | Prophylaxis Cohort: SoC |
|---|---|---|---|
| PK-I: ADAMTS13 Activity | 1.003 ± 0.235 | NA ± NA | 0.192 ± 0.102 |
| PK-II: ADAMTS13 Activity | 1.130 ± 0.253 | 1.162 ± 0.250 | — |
| PK-III: ADAMTS13 Activity | — | 1.036 ± 0.253 | — |
µg/mL stands for microgram per milliliter. PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
| µg/mL | Prophylaxis Cohort: TAK-755-ORT | Prophylaxis Cohort: TAK-755 SIN | Prophylaxis Cohort: SoC |
|---|---|---|---|
| PK-I: ADAMTS13 Antigen | 0.713 ± 0.145 | NA ± NA | 0.141 ± 0.0710 |
| PK-II: ADAMTS13 Antigen | 0.804 ± 0.185 | 0.844 ± 0.168 | — |
| PK-III: ADAMTS13 Antigen | — | 0.715 ± 0.203 | — |
VWF:Ag is a measure of total VWF protein and was assessed using a sandwich ELISA employing polyclonal anti-human-VWF antibodies. Assessments of VWF:Ag at baseline and following infusion of the SoC agent and TAK-755 treatment during the initial PK assessment were reported. PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
| percentage of VWF:Ag | Prophylaxis Cohort: TAK-755-ORT | Prophylaxis Cohort: TAK-755 SIN | Prophylaxis Cohort: SoC |
|---|---|---|---|
| VWF:Ag : PK-I | -0.11 ± 17.064 | — | 3.67 ± 19.705 |
| VWF:Ag : PK-II | 0.48 ± 34.798 | -1.31 ± 22.259 | — |
VWF:RCo provides a measure of the ability of VWF to bind platelet glycoprotein Ib. Stabilized platelets are agglutinated in the presence of VWF and the antibiotic Ristocetin. Assessments of VWF:RCo at baseline and following infusion of the SoC agent and TAK-755 treatment during the initial PK assessment was reported. PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
| percentage of VWF:RCo | Prophylaxis Cohort: TAK-755-ORT | Prophylaxis Cohort: TAK-755 SIN | Prophylaxis Cohort: SoC |
|---|---|---|---|
| VWF:RCo- PK-I | 3.63 ± 42.178 | — | 9.99 ± 33.230 |
| VWF:RCo- PK-II | 7.45 ± 31.917 | 3.60 ± 30.678 | — |
PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
| IU/mL | Prophylaxis Cohort: TAK-755 ORT | Prophylaxis Cohort: TAK-755 SIN | Prophylaxis Cohort: SoC |
|---|---|---|---|
| ADAMTS13 Activity: PK-I | NA ± NA | NA ± NA | NA ± NA |
| ADAMTS13 Activity: PK-II | NA ± NA | NA ± NA | — |
| ADAMTS13 Activity: PK-III | — | NA ± NA | — |
PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
| percentage of VWF:RCo | Prophylaxis Cohort: TAK-755-ORT | Prophylaxis Cohort: TAK-755-SIN | Prophylaxis Cohort: SoC |
|---|---|---|---|
| PK-I: VWF:RCo | 145.54 ± 54.698 | 137.62 ± 52.978 | 148.46 ± 51.415 |
| PK-II: VWF:RCo | 155.76 ± 63.032 | 154.98 ± 74.444 | — |
PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
| percentage of VWF:Ag | Prophylaxis Cohort: TAK-755-ORT | Prophylaxis Cohort: TAK-755-SIN | Prophylaxis Cohort: SoC |
|---|---|---|---|
| PK-I: VWF:Ag | 110.38 ± 45.205 | NA ± NA | 105.07 ± 40.539 |
| PK-II: VWF:Ag | 120.48 ± 49.224 | 116.66 ± 60.338 | — |
PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
| % of VWF:mm Low Res.Intermediate | Prophylaxis Cohort: TAK-755-ORT | Prophylaxis Cohort: TAK-755-SIN | Prophylaxis Cohort: SoC |
|---|---|---|---|
| PK-I: VWF:mm Low Res. Intermediate | 32.14 ± 3.375 | NA ± NA | 31.22 ± 2.955 |
| PK-II: VWF:mm Low Res. Intermediate | 30.87 ± 3.754 | 31.10 ± 3.616 | — |
PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
| % of VWF:mm Low Res. Large | Prophylaxis Cohort: TAK-755-ORT | Prophylaxis Cohort: TAK-755-SIN | Prophylaxis Cohort: SoC |
|---|---|---|---|
| PK-I: VWF:mm Low Res. Large | 45.98 ± 5.920 | NA ± NA | 46.03 ± 5.043 |
| PK-II: VWF:mm Low Res. Large | 46.17 ± 5.670 | 44.93 ± 7.319 | — |
PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
| % of VWF:mm Low Res. Small | Prophylaxis Cohort: TAK-755-ORT | Prophylaxis Cohort: TAK-755-SIN | Prophylaxis Cohort: SoC |
|---|---|---|---|
| PK-I: VWF:mm Low Res. Small | 21.66 ± 4.230 | NA ± NA | 22.77 ± 5.161 |
| PK-II: VWF:mm Low Res. Small | 22.96 ± 3.047 | 23.96 ± 5.320 | — |
Total binding antibodies to ADAMTS13 were measured by an ELISA-based assay, detecting total immunoglobulins (IgG, IgA, and IgM). As per planned analysis, data for this outcome measure were collected and reported per sequence (Prophylaxis Cohort I: TAK-755 Then SoC and Prophylaxis Cohort II: SoC Then TAK-755) for the prophylaxis cohorts only.
| Participants | Prophylaxis Cohort I: TAK-755 Then SoC | Prophylaxis Cohort II: SoC Then TAK-755 |
|---|---|---|
| Number of Participants With Total Binding Antibodies to ADAMTS13 During Prophylactic Treatment | 0 | 2 |
Neutralizing antibodies were measured by a Bethesda method with Nijmegen modification using the ADAMTS13 FRETS-VWF73 activity assay. As per planned analysis, data for this outcome measure were collected and reported per sequence (Prophylaxis Cohort I: TAK-755 Then SoC and Prophylaxis Cohort II: SoC Then TAK-755) for the prophylaxis cohorts only.
| Participants | Prophylaxis Cohort I: TAK-755 Then SoC | Prophylaxis Cohort II: SoC Then TAK-755 |
|---|---|---|
| Number of Participants With Neutralizing Antibodies to ADAMTS13 During Prophylactic Treatment | 0 | 1 |
Total immunoglobulin antibodies (Immunoglobulin G \[IgG\], A \[IgA\], and M \[IgM\]) against CHO protein were analyzed using ELISA assay. As per planned analysis, data for this outcome measure were collected and reported per sequence (Prophylaxis Cohort I: TAK-755 Then SoC and Prophylaxis Cohort II: SoC Then TAK-755) for the prophylaxis cohorts only.
| Participants | Prophylaxis Cohort I: TAK-755 Then SoC | Prophylaxis Cohort II: SoC Then TAK-755 |
|---|---|---|
| Number of Participants With Anti-Chinese Hamster Ovary (Anti-CHO) Protein Antibodies During Prophylactic Treatment | 0 | 2 |
The cTTP-PEQ consists of 26 questions designed to assess the participant's experience of fatigue, joint, muscle, abdominal \&chest pain in the previous 24 hours, neurologic manifestations, bruising, feelings of depression and mood alterations, and activity limitation in the past 7 days, and participant's attitudes, experienced side effects, work/school absences and travel impact associated with treatment received for TTP during the previous 2 weeks. The cTTP PEQ is focused on measuring the symptoms and impacts of disease. The total scores range from 0 to 162. A higher score indicates greater burden and poor quality of life. As per planned analysis,for the prophylaxis cohorts the data for this outcome measure were collected and reported by categorizing as per Prophylaxis Periods and per age groups,≥12 years,12 to 18 years,≥18 years for both on demand(OD) and prophylaxis cohorts. No participants in the OD Cohorts had cTTP-PEQ data available for analysis at scheduled post-baseline visits.
| score on a scale | Prophylaxis Cohort: TAK-755 | Prophylaxis Cohort: SoC | On Demand Cohort I: TAK-755 | On Demand Cohort II: SoC |
|---|---|---|---|---|
| ≥12 years: Total Score, End of Period 1 | -2.6 ± 24.17 | -2.2 ± 12.47 | — | — |
| ≥12 years: Total Score, End of Period 2 | -10.4 ± 18.13 | -1.4 ± 18.38 | — | — |
| ≥12 years: Total Score, End of Period 3 | -10.6 ± 13.13 | — | — | — |
| 12 to < 18 years: Total Score, End of Period 1 | — | 12.0 ± NA | — | — |
| 12 to < 18 years: Total Score, End of Period 2 | 13.0 ± NA | — | — | — |
| 12 to < 18 years: Total Score, End of Period 3 | -6.0 ± NA | — | — | — |
| ≥18 years: Total Score, End of Period 1 | -2.6 ± 24.17 | -3.5 ± 12.22 | — | — |
| ≥18 years: Total Score, End of Period 2 | -12.5 ± 17.37 | -1.4 ± 18.38 | — | — |
| ≥18 years: Total Score, End of Period 3 | -10.9 ± 13.41 | — | — | — |
SF-36v2 is questionnaire that evaluated participant's health related quality of life. It included 36 questions related to 8 health dimensions: physical functioning, role-physical(role limitations due to physical health problems), bodily pain, general health, vitality(energy/fatigue),social functioning, role-emotional(role limitations due to emotional problems),\& mental health. Based on these 4 scales(physical functioning, role-physical, bodily pain, general health), physical component score was generated which ranges between 0 \&100, with higher scores indicating a better quality of life. Based on these 4 scales(vitality, social functioning, role-emotional,\&mental health), mental component score was generated ranging between 0\&100, with higher scores=better quality of life. As per planned analysis, for the prophylaxis cohorts data for this outcome measure were collected\&reported by categorizing as per Prophylaxis Periods and per component scores for both on demand\&prophylaxis cohorts.
| score on a scale | Prophylaxis Cohort: TAK-755 | Prophylaxis Cohort: SoC | On Demand Cohort I: TAK-755 | On Demand Cohort II: SoC |
|---|---|---|---|---|
| Physical Component Score: End of Period 1 | 3.934 ± 10.1098 | -0.532 ± 4.8297 | — | — |
| Physical Component Score: End of Period 2 | 3.121 ± 6.3196 | 2.625 ± 6.4219 | — | — |
| Physical Component Score: End of Period 3 | 1.019 ± 4.8970 | — | — | — |
| Mental Component Score: End of Period 1 | -7.263 ± 7.4244 | 5.418 ± 5.0244 | — | — |
| Mental Component Score: End of Period 2 | 2.880 ± 5.2646 | -4.853 ± 9.9302 | — | — |
| Mental Component Score: End of Period 3 | 3.852 ± 7.4066 | — | — | — |
TSQM is a treatment satisfaction measure used to assess the overall level of participant's satisfaction or dissatisfaction with their medications. TSQM-9 is a 9-item, validated, self-administered instrument used to assess participant's satisfaction with medication. The three domains assessed are treatment effectiveness, convenience, and global satisfaction. The score of each of the 3 domains is based on an algorithm to create a score of 0 to 100. Higher score indicates greater satisfaction in that domain. As per planned analysis, for the prophylaxis cohorts data for this outcome measure were collected and reported by categorizing as per Prophylaxis Periods and per domain scores for both on demand and prophylaxis cohorts.
| score on a scale | Prophylaxis Cohort: TAK-755 | Prophylaxis Cohort: SoC | On Demand Cohort I: TAK-755 | On Demand Cohort II: SoC |
|---|---|---|---|---|
| Treatment Effectiveness Score: End of Period 1 | 26.8519 ± 36.07548 | 4.4444 ± 13.55778 | — | — |
| Treatment Effectiveness Score: End of Period 2 | 25.0000 ± 17.42119 | 12.9630 ± 17.09330 | — | — |
| Treatment Effectiveness Score: End of Period 3 | 22.2222 ± 20.11626 | — | — | — |
| Convenience Score: End of Period 1 | 36.1111 ± 16.75900 | 1.6667 ± 11.43059 | — | — |
| Convenience Score: End of Period 2 | 27.7778 ± 15.27076 | 14.8148 ± 27.81479 | — | — |
| Convenience Score: End of Period 3 | 21.0526 ± 29.48919 | — | — | — |
| Global Satisfaction Score: End of Period 1 | 28.5714 ± 9.03508 | 5.0000 ± 16.85270 | — | — |
| Global Satisfaction Score: End of Period 2 | 23.5714 ± 16.85270 | 14.2857 ± 21.66536 | — | — |
| Global Satisfaction Score: End of Period 3 | 22.9323 ± 16.07433 | — | — | — |
EQ-5D-3L health questionnaire is a participant-answered questionnaire scoring 5 dimensions(domains) - mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is scored on an ordinal scale with 3 available levels of response and scores ranging from 1 to 3, "no problems," "some problems," and "extreme problems," respectively. Lower scores for the domains in the EQ-5D-3L indicate improvement. As per planned analysis, for the prophylaxis cohorts data for this outcome measure were collected and reported by categorizing as per Prophylaxis Periods and per domain scores for both on demand and prophylaxis cohorts.
| score on a scale | Prophylaxis Cohort: TAK-755 | Prophylaxis Cohort: SoC | On Demand Cohort I: TAK-755 | On Demand Cohort II: SoC |
|---|---|---|---|---|
| Mobility: End of Period 1 | 0.3 ± 0.46 | -0.1 ± 0.32 | — | — |
| Mobility: End of Period 2 | -0.1 ± 0.30 | 0.0 ± 0.00 | — | — |
| Mobility: End of Period 3 | -0.1 ± 0.23 | — | — | — |
| Self-Care: End of Period 1 | 0.1 ± 0.35 | 0.0 ± 0.00 | — | — |
| Self-Care: End of Period 2 | 0.0 ± 0.00 | 0.0 ± 0.00 | — | — |
| Self-Care: End of Period 3 | -0.1 ± 0.23 | — | — | — |
| Usual Activities: End of Period 1 | 0.0 ± 0.53 | -0.2 ± 0.42 | — | — |
| Usual Activities: End of Period 2 | 0.0 ± 0.45 | 0.0 ± 0.63 | — | — |
| Usual Activities: End of Period 3 | -0.1 ± 0.40 | — | — | — |
| Pain/Discomfort: End of Period 1 | 0.3 ± 0.46 | -0.2 ± 0.63 | — | — |
| Pain/Discomfort: End of Period 2 | -0.3 ± 0.65 | 0.2 ± 0.41 | — | — |
| Pain/Discomfort: End of Period 3 | -0.2 ± 0.54 | — | — | — |
| Anxiety/Depression: End of Period 1 | 0.1 ± 0.64 | 0.0 ± 0.00 | — | — |
| Anxiety/Depression: End of Period 2 | -0.1 ± 0.30 | 0.0 ± 0.00 | — | — |
| Anxiety/Depression: End of Period 3 | -0.1 ± 0.46 | — | — | — |
EQ-5D-Y health questionnaire is a participant answered questionnaire scoring 5 dimensions (domains) - mobility, self-care, usual activities, pain/discomfort and anxiety/depression assessed in participants aged from 8 to 16 years. The EQ-5D-Y descriptive system includes 5 descriptive items: Mobility, self-care, doing usual activities, having pain or discomfort, and feeling anxiety or depressed. Each dimension is scored at 3 levels: 1=No problems, 2=some problems, and 3=a lot of problems. Lower scores for the domains in the EQ-5D-Y indicate improvement. As per planned analysis, for the prophylaxis cohorts data for this outcome measure were collected and reported by categorizing as per Prophylaxis Periods and per domain scores for both on demand and prophylaxis cohorts.
| score on a scale | Prophylaxis Cohort: TAK-755 | Prophylaxis Cohort: SoC | On Demand Cohort I: TAK-755 | On Demand Cohort II: SoC |
|---|---|---|---|---|
| Mobility: End of Period 1 | 0.0 ± NA | 0.0 ± 0.00 | — | — |
| Mobility: End of Period 2 | 0.0 ± 0.00 | 0.0 ± NA | — | — |
| Mobility: End of Period 3 | 0.0 ± 0.00 | — | — | — |
| Self-Care: End of Period 1 | 0.0 ± NA | 0.0 ± 0.00 | — | — |
| Self-Care: End of Period 2 | 0.0 ± 0.00 | 0.0 ± NA | — | — |
| Self-Care: End of Period 3 | 0.0 ± 0.00 | — | — | — |
| Usual Activities: End of Period 1 | 0.0 ± NA | 0.0 ± 0.00 | — | — |
| Usual Activities: End of Period 2 | 0.0 ± 0.00 | 0.0 ± NA | — | — |
| Usual Activities: End of Period 3 | 0.0 ± 0.00 | — | — | — |
| Pain/Discomfort: End of Period 1 | 1.0 ± NA | -0.7 ± 0.58 | — | — |
| Pain/Discomfort: End of Period 2 | -0.7 ± 0.58 | 0.0 ± NA | — | — |
| Pain/Discomfort: End of Period 3 | -0.3 ± 0.96 | — | — | — |
| Anxiety/Depression: End of Period 1 | 0.0 ± NA | 0.0 ± 0.00 | — | — |
| Anxiety/Depression: End of Period 2 | 0.3 ± 0.58 | 0.0 ± NA | — | — |
| Anxiety/Depression: End of Period 3 | 0.0 ± 0.00 | — | — | — |
The PedsQL is a generic health related quality of life instrument designed specifically for a pediatric population and captures following domains: physical functioning, emotional functioning, social functioning, school functioning, psychosocial summary, physical health and total score. The Peds-QL total score consists of all 23 items of all domains. This modular instrument uses a 5-point scale: from 0 (never) to 4 (almost always). Items are reversed scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. Higher scores indicate better quality of life. As per planned analysis, for the prophylaxis cohorts data for this outcome measure were collected and reported by categorizing as per Prophylaxis Periods and per age groups, 2 to \< 5 years, 5 to \< 8 years, 8 to \< 13 years, and 13 to \< 18 years, for both on demand and prophylaxis cohorts.
| score on a scale | Prophylaxis Cohort: TAK-755 | Prophylaxis Cohort: SoC | On Demand Cohort I: TAK-755 | On Demand Cohort II: SoC |
|---|---|---|---|---|
| 2 to < 5 years, End of Period 1 | 25.0000 ± 47.14045 | — | — | — |
| 2 to < 5 years, End of Period 2 | — | 27.3810 ± 47.14045 | — | — |
| 2 to < 5 years, End of Period 3 | 24.4048 ± 49.66583 | — | — | — |
| 5 to < 8 years, End of Period 1 | 29.3478 ± NA | -16.3043 ± NA | — | — |
| 5 to < 8 years, End of Period 2 | -6.5217 ± NA | 32.6087 ± NA | — | — |
| 5 to < 8 years, End of Period 3 | 17.9348 ± 19.21486 | — | — | — |
| 8 to < 13 years, End of Period 1 | -2.1739 ± NA | 15.2174 ± 13.83470 | — | — |
| 8 to < 13 years, End of Period 2 | 8.6957 ± 23.05783 | 1.0870 ± NA | — | — |
| 8 to < 13 years, End of Period 3 | 5.7971 ± 7.39876 | — | — | — |
The annualized number of days participants stayed in hospital for acute TTP events were assessed. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts in a combined manner for Periods 1 and 2 for SoC treatment and for Periods 1, 2, and 3 for TAK-755 treatment respectively.
| days/year | Prophylaxis Cohort: TAK-755 | Prophylaxis Cohort: SoC |
|---|---|---|
| Resource Utilization: Annualized Length of Hospital Stay for Acute TTP Events for Prophylaxis Cohorts | 0.00 (0.0 to 0.0) | 0.00 (0.0 to 3.4) |
Annualized number of acute care visits was calculated as the number of acute care visits × 365.25/(End date - treatment start date + 1). As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts in a combined manner for Periods 1 and 2 for SoC treatment and for Periods 1, 2, and 3 for TAK-755 treatment respectively.
| acute care visits per year | Prophylaxis Cohort: TAK-755 | Prophylaxis Cohort: SoC |
|---|---|---|
| Resource Utilization: Annualized Number of Acute Care Visits for Prophylaxis Cohorts | 0.60 ± 1.331 | 0.14 ± 0.498 |
Annualized number of days missed from school or work were assessed. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts in a combined manner for Periods 1 and 2 for SoC treatment and for Periods 1, 2, and 3 for TAK-755 treatment respectively.
| days/year | Prophylaxis Cohort: TAK-755 | Prophylaxis Cohort: SoC |
|---|---|---|
| Resource Utilization: Annualized Number of Days Missed From School or Work for Prophylaxis Cohorts | 0.00 (0.0 to 180.3) | 0.00 (0.0 to 294.5) |
Collected over From first dose of study drug up to end of study (79.6 months). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Prophylaxis Cohort: TAK-755 | 0/47 (0%) | 6/47 (12.8%) | 39/47 (83%) |
| Prophylaxis Cohort: SoC | 0/48 (0%) | 8/48 (16.7%) | 37/48 (77.1%) |
| On Demand Cohort I: TAK-755 | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) |
| On Demand Cohort II: SoC | 0/4 (0%) | 1/4 (25%) | 3/4 (75%) |
| Event | Prophylaxis Cohort: TAK-755 | Prophylaxis Cohort: SoC | On Demand Cohort I: TAK-755 | On Demand Cohort II: SoC |
|---|---|---|---|---|
| ThrombocytopeniaBlood and lymphatic system disorders | 0/47 | 2/48 | 0/2 | 1/4 |
| Abdominal painGastrointestinal disorders | 1/47 | 0/48 | 0/2 | 0/4 |
| Adnexal torsionReproductive system and breast disorders | 1/47 | 0/48 | 0/2 | 0/4 |
| Gastroenteritis clostridialInfections and infestations | 1/47 | 0/48 | 0/2 | 0/4 |
| HyperthyroidismEndocrine disorders | 1/47 | 0/48 | 0/2 | 0/4 |
| Ovarian cystReproductive system and breast disorders | 1/47 | 0/48 | 0/2 | 0/4 |
| PneumoniaInfections and infestations | 1/47 | 0/48 | 0/2 | 0/4 |
| TachycardiaCardiac disorders | 1/47 | 0/48 | 0/2 | 0/4 |
| Thrombotic thrombocytopenic purpuraBlood and lymphatic system disorders | 1/47 | 0/48 | 0/2 | 0/4 |
| HeadacheNervous system disorders | 0/47 | 1/48 | 0/2 | 0/4 |
| Event | Prophylaxis Cohort: TAK-755 | Prophylaxis Cohort: SoC | On Demand Cohort I: TAK-755 | On Demand Cohort II: SoC |
|---|---|---|---|---|
| HeadacheNervous system disorders | 15/47 | 10/48 | 0/2 | 1/4 |
| Allergic transfusion reactionInjury, poisoning and procedural complications | 0/47 | 7/48 | 0/2 | 1/4 |
| Blood lactate dehydrogenase increasedInvestigations | 4/47 | 1/48 | 0/2 | 1/4 |
| HypoaesthesiaNervous system disorders | 4/47 | 0/48 | 0/2 | 1/4 |
| NauseaGastrointestinal disorders | 8/47 | 2/48 | 0/2 | 1/4 |
| ParaesthesiaNervous system disorders | 1/47 | 2/48 | 0/2 | 1/4 |
| PetechiaeSkin and subcutaneous tissue disorders | 0/47 | 0/48 | 0/2 | 1/4 |
| PruritusSkin and subcutaneous tissue disorders | 2/47 | 3/48 | 0/2 | 1/4 |
| ThrombocytopeniaBlood and lymphatic system disorders | 3/47 | 3/48 | 0/2 | 1/4 |
| Tooth abscessInfections and infestations | 1/47 | 0/48 | 0/2 | 1/4 |
The Safety Analysis Set included all participants treated with at least 1 dose of TAK-755 or SoC treatment after randomization. Two participants randomized to Prophylaxis Cohort I received actual treatment as per Prophylaxis Cohort II and are presented per actual treatment arm.
| Age, Customized(Participants) | Prophylaxis Cohort I: TAK-755 Then SoC | Prophylaxis Cohort II: SoC Then TAK-755 | On Demand Cohort I: TAK-755 | On Demand Cohort II: SoC | Total |
|---|---|---|---|---|---|
| Prophylaxis Cohort — ≥18 years | 16 | 20 | 0 | 0 | 36 |
| Prophylaxis Cohort — 12 to <18 years | 1 | 3 | 0 | 0 | 4 |
| Prophylaxis Cohort — 6 to <12 years | 1 | 3 | 0 | 0 | 4 |
| Prophylaxis Cohort — <6 years | 3 | 1 | 0 | 0 | 4 |
| On Demand Cohort — ≥18 years | 0 | 0 | 2 | 3 | 5 |
| On Demand Cohort — 12 to <18 years | 0 | 0 | 0 | 0 | 0 |
| On Demand Cohort — 6 to <12 years | 0 | 0 | 0 | 0 | 0 |
| On Demand Cohort — <6 years | 0 | 0 | 0 | 1 | 1 |
| Sex: Female, Male(Participants) | Prophylaxis Cohort I: TAK-755 Then SoC | Prophylaxis Cohort II: SoC Then TAK-755 | On Demand Cohort I: TAK-755 | On Demand Cohort II: SoC | Total |
|---|---|---|---|---|---|
| Prophylaxis Cohort — Female | 12 | 16 | 0 | 0 | 28 |
| Prophylaxis Cohort — Male | 9 | 11 | 0 | 0 | 20 |
| On Demand Cohort — Female | 0 | 0 | 1 | 1 | 2 |
| On Demand Cohort — Male | 0 | 0 | 1 | 3 | 4 |
| Ethnicity (NIH/OMB)(Participants) | Prophylaxis Cohort I: TAK-755 Then SoC | Prophylaxis Cohort II: SoC Then TAK-755 | On Demand Cohort I: TAK-755 | On Demand Cohort II: SoC | Total |
|---|---|---|---|---|---|
| Prophylaxis Cohort — Hispanic or Latino | 1 | 0 | 0 | 0 | 1 |
| Prophylaxis Cohort — Not Hispanic or Latino | 16 | 23 | 0 | 0 | 39 |
| Prophylaxis Cohort — Unknown or Not Reported | 4 | 4 | 0 | 0 | 8 |
| On Demand Cohort — Hispanic or Latino | 0 | 0 | 0 | 0 | 0 |
| On Demand Cohort — Not Hispanic or Latino | 0 | 0 | 2 | 4 | 6 |
| On Demand Cohort — Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Prophylaxis Cohort I: TAK-755 Then SoC | Prophylaxis Cohort II: SoC Then TAK-755 | On Demand Cohort I: TAK-755 | On Demand Cohort II: SoC | Total |
|---|---|---|---|---|---|
| Prophylaxis Cohort — American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 |
| Prophylaxis Cohort — Asian | 2 | 3 | 0 | 0 | 5 |
| Prophylaxis Cohort — Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 |
| Prophylaxis Cohort — Black or African American | 0 | 1 | 0 | 0 | 1 |
| Prophylaxis Cohort — White | 15 | 17 | 0 | 0 | 32 |
| Prophylaxis Cohort — More than one race | 0 | 1 | 0 | 0 | 1 |
| Prophylaxis Cohort — Unknown or Not Reported | 4 | 5 | 0 | 0 | 9 |
| On Demand Cohort — American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 |
| On Demand Cohort — Asian | 0 | 0 | 1 | 0 | 1 |
| On Demand Cohort — Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 |
| On Demand Cohort — Black or African American | 0 | 0 | 0 | 1 | 1 |
| On Demand Cohort — White | 0 | 0 | 1 | 2 | 3 |
| On Demand Cohort — More than one race | 0 | 0 | 0 | 1 | 1 |
| On Demand Cohort — Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Supporting information: Study protocol, Sap, Icf, Csr
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