A Phase 3 interventional study of rVWF and rFVIII in Von Willebrand Disease (VWD), sponsored by Baxalta now part of Shire. Completed at 33 sites in 9 countries. Open to participants aged 0 Years and older. Per ClinicalTrials.gov, last updated 2025-09-03.
Sponsored by Baxalta now part of Shire (part of Takeda) · Phase 3, Interventional, and Prevention
The main aim of the study is to check effectiveness of rVWF (vonicog alfa) prophylaxis based on the annualized bleeding rate (ABR) of spontaneous (not related to trauma) bleeding episodes in pediatric and adult participants during the first 12 months on study treatment.
The participants will be treated with rVWF for a maximum of 3 years. Their von Willebrand Disease will be treated according to Investigational product (IP) dosing directions.
96 studies on the registry are indexed under von Willebrand Diseases; 25 are open to participants now.
This study's enrollment of 38 is above the median of 25 across 41 interventional studies indexed under von Willebrand Diseases.
Browse von Willebrand Diseases studies →Baxalta now part of Shire is the lead sponsor of 111 studies on the registry; none are open to participants now.
Of its 18 completed or terminated interventional studies of FDA-regulated products, 16 (89%) have results posted.
First submitted before Baxalta became part of Takeda.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
The participant will not be considered eligible for the study without meeting all of the criteria below.
Participants who have completed Study 071301 or Study 071102 (or participants who have completed the surgery arm treatment in Study 071102 and want to continue to receive on-demand (OD) treatment) and are willing to immediately transition into this study, must meet the following 2 criteria to be eligible for this study:
New participants (Cohort 4) who meet the above 2 and ALL the following additional criteria are eligible for this study:
- Participant has a documented diagnosis of severe von Willebrand disease (VWD) (baseline von Willebrand factor: Ristocetin cofactor (VWF:RCo) \<20 International Units per deciliter [IU/dL]) with a history of requiring substitution therapy with von Willebrand factor (vWF) concentrate to control bleeding:
Diagnosis is confirmed by genetic testing and multimer analysis, documented in participant history or at screening.
Exclusion Criteria:
The participant will be excluded from the study if any of the following exclusion criteria are met.
Delay criteria Only for Cohort 4, if the participant presents with an acute bleeding episodes or acute illness (eg, influenza, flu-like syndrome, allergic rhinitis/conjunctivitis, and non-seasonal asthma) the screening visit will be postponed until the participant has recovered. For all other participants, end of study (EOS) visit for 071102 or 071301 will be completed per protocol and the completed EOS in Study 071102 or 071301 will also serve as the screening visit for this continuation study (SHP677-304).
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Child-Pugh class
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants will receive recombinant von Willebrand factor (rVWF) (with or without ADVATE).
Biological: rVWF · Biological: rFVIII
Participants will receive recombinant von Willebrand factor (rVWF).
Biological: rVWF · Biological: rFVIII
Spontaneous Annualized Bleeding Rate (sABR)
sABR was derived as \[number of treated bleeds\] / \[duration in years\]. Bleeds with unknown causality were considered as spontaneous. Bleeds were categorized based on the investigator assessment of cause. sABR during the first 12 months of prophylactic treatment with rVWF (vonicog alfa) was reported.
Time frame: Up to 12 months
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
An adverse event (AE): any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to medicinal product. TEAE was defined as any AE that started after the first administration of study drug in this continuation study. Serious TEAEs: any untoward medical occurrence that: 1) results in death, 2) is life-threatening, 3) requires inpatient hospitalization or prolongation of existing hospitalization, 4) results in persistent or significant disability/incapacity, 5) leads to a congenital anomaly/birth defect in the offspring of the participant or 6) is medically important.
Time frame: Up to 5.8 years
Number of Participants Based on Severity of TEAEs
An AE is defined as any untoward medical occurrence in a participant administered IP that does not necessarily have a causal relationship with the treatment. TEAE was defined as any AE that started after the first administration of study drug in this continuation study. Severity of TEAEs was determined by following definitions: Mild: No limitation of usual activities; Moderate: Some limitation of usual activities and may required therapeutic intervention; Severe: Inability to carry out usual activities with sequelae, which required therapeutic intervention. Number of participants with TEAEs based on severity of TEAEs were reported.
Time frame: Up to 5.8 years
Number of Participants Based on Causality of TEAEs
An AE is defined as any untoward medical occurrence in a participant administered IP that does not necessarily have a causal relationship with the treatment. TEAE was defined as any AE that started after the first administration of study drug in this continuation study. A physician/investigator made the assessment of relationship to investigational product for each AE. Number of participants with TEAEs based on causality were reported.
Time frame: Up to 5.8 years
Number of Participants With Thromboembolic Events
Thromboembolism defined as formation of a clot (thrombus) in a blood vessel that breaks loose, is carried by the blood stream and could plug another vessel. Number of participants with thromboembolic events as TEAEs of special interest were reported.
Time frame: Up to 5.8 years
Number of Participants With Hypersensitivity Reactions
Hypersensitivity (also called hypersensitivity reaction or intolerance) defined as undesirable reactions produced by the normal immune system, including allergies and autoimmunity. Potential hypersensitivity events were identified by broad search criteria and then medically assessed. Number of participants with hypersensitivity reactions as TEAEs of special interest was calculated.
Time frame: Up to 5.8 years
Number of Participants Who Developed Neutralizing Antibodies to Von Willebrand Factor (VWF)
Three functional VWF assays for von Willebrand factor collagen binding (VWF:CB), von Willebrand factor: Ristocetin Cofactor (VWF:RCo) and von Willebrand factor VIII B (VWF:FVIIIB) were used to test the presence of neutralizing anti-VWF antibodies. Neutralizing antibodies to VWF:RCo, VWF:CB and VWF:FVIIIB activities were measured by assays based on the Bethesda assay established for quantitative analysis of FVIII inhibitors (Nijmegen modification of the Bethesda assay). Only confirmed neutralizing anti -VWF antibodies were considered inhibitors. Number of participants who developed neutralizing antibodies to rVWF were assessed.
Time frame: Up to 5.8 years
Number of Participants Who Developed Neutralizing Antibodies to Factor VIII (FVIII)
Three functional VWF assays for von Willebrand factor collagen binding (VWF:CB), von Willebrand factor: Ristocetin Cofactor (VWF:RCo) and von Willebrand factor VIII B (VWF:FVIIIB) were used to test the presence of neutralizing anti-VWF antibodies. Neutralizing antibodies to VWF:RCo, VWF:CB and VWF:FVIIIB activities was measured by assays based on the Bethesda assay established for quantitative analysis of FVIII inhibitors (Nijmegen modification of the Bethesda assay). Only confirmed neutralizing anti -VWF antibodies were considered inhibitors. Number of participants who developed neutralizing antibodies to FVIII were assessed.
Time frame: Up to 5.8 years
Number of Participants Who Developed Total Binding Antibodies to Von Willebrand Factor (VWF)
The presence of total binding anti-VWF antibodies was determined by an enzyme-linked immunosorbent assay (ELISA) employing polyclonal anti-human Immunoglobulin (Ig) antibodies (IgG, IgM and IgA). Number of participants who developed of total binding antibodies to rVWF were assessed.
Time frame: Up to 5.8 years
Number of Participants Who Developed Total Binding Antibodies to Factor VIII (FVIII)
Binding antibodies against FVIII were analyzed using a proprietary enzyme immunoassay. Number of participants who developed of total binding antibodies to FVIII were assessed.
Time frame: Up to 5.8 years
Number of Participants Who Developed Binding Antibodies to Chinese Hamster Ovary (CHO) Proteins
Total Ig antibodies (IgG, IgA, IgM) against CHO protein were analyzed using ELISA. Number of participants who developed binding antibodies to CHO proteins were assessed.
Time frame: Up to 5.8 years
Number of Participants Who Developed Binding Antibodies to Mouse Immunoglobulin G (IgG)
Detection and quantification of IgG antibodies originating from human plasma that were directed against mouse-IgG (HAMA: human anti- mouse antibodies) were assessed using ELISA (Medac, Hamburg, Germany). Number of participants who developed binding antibodies to Mouse IgG were assessed.
Time frame: Up to 5.8 years
Number of Participants Who Develop Binding Antibodies to Recombinant Furin (rFurin)
Total Ig antibodies (IgG, IgA, IgM) against human furin were analyzed using ELISA. Number of participants who developed binding antibodies to rFurin were assessed.
Time frame: Up to 5.8 years
Number of Participants With Clinically Significant Changes in Vital Signs
Vital signs included blood pressure (systolic and diastolic), pulse rate, respiratory rate and body temperature. Number of participants with clinically significant change from baseline in vital signs were assessed.
Time frame: Up to 5.8 years
Number of Participants With Clinically Significant Changes in Laboratory Parameters
Clinical laboratory parameters included serum chemistry, hematology and urinalysis assessments. Number of participants with clinically significant change from baseline in clinical laboratory parameters were assessed.
Time frame: Up to 5.8 years
Spontaneous Annualized Bleeding Rate (sABR) Under Prophylactic Treatment
sABR was derived as \[number of treated bleeds\] / \[duration in years\]. Bleeds with unknown causality were considered as spontaneous. Bleeds were categorized based on the investigator assessment of cause. sABR during prophylaxis treatment with rVWF (vonicog alfa) while enrolled in the study were reported.
Time frame: Up to 5.8 years
Number of Participants Categorized Based on Weekly Number of Infusions
Categorized as ≥ 0 to \< 1 infusion per week, ≥ 1 to \< 2 infusions per week, ≥ 2 to \< 3 infusions per week, ≥ 3 infusions per week. The number of participants categorized based on number of infusions per week during prophylactic treatment with rVWF (vonicog alfa) were reported.
Time frame: Up to 5.8 years
Number of Participants Categorized Based on Spontaneous Annualized Bleeding Rate (sABR)
The sABR was the number of spontaneous bleeds divided by the observation period in years, where an observation period = (date of completion/termination-date of first dose+1)/365.2425. sABR was categorized based on number of BEs as 0, greater than (\>) 0 through 2, \>2 through 5, \>5 during the prophylactic treatment with rVWF (vonicog alfa). Bleeding at multiple locations related to the same injury was counted as single BE. BEs of unknown cause were counted as spontaneous bleeds. Number of participants categorized based on sABR during prophylactic treatment with rVWF (vonicog alfa) were reported.
Time frame: Up to 5.8 years
Time to First Bleeding Event on Prophylaxis Treatment
Time to event estimates and confidence intervals obtained from Kaplan-Meier analysis. Participants with 0 bleeds during each study period were censored at the date of the last day in that study period.
Time frame: Up to 5.8 years
Spontaneous Annualized Bleeding Rate (sABR) by Location of Bleeding
sABR was derived as \[number of treated bleeds\] / \[duration in years\]. sABR for BEs based on location of bleeding: Skin, Muscle, Mucosal Nasal, Mucosal Oral, Joint, Gastrointestinal (GI), Menstrual/Heavy Menstrual, Venipuncture Site, Soft Tissue, Body Cavity, Hematuria, Central Nervous System (CNS) and Other, while on prophylactic treatment with rVWF (vonicog alfa) were reported.
Time frame: Up to 5.8 years
Total Number of Infusions During Prophylactic Treatment
Total number of infusions during prophylactic treatment with rVWF (vonicog alfa) were reported.
Time frame: Up to 5.8 years
Average Number of Infusions Per Week During Prophylactic Treatment
Average number of infusions per week during prophylactic treatment with rVWF (vonicog alfa) were reported.
Time frame: Up to 5.8 years
Total Weight Adjusted Consumption of Recombinant Von Willebrand Factor (rVWF) (Vonicog Alfa) Per Participant During Prophylactic Treatment
For each participant, the body weight-adjusted dose (IU/kg) was derived as the number of units of rVWF infused (IU) divided by the last available body weight (kilogram \[kg\]) prior to the infusion. Total weight adjusted consumption of rVWF (vonicog alfa) per participant during prophylactic treatment with rVWF (vonicog alfa) was reported as International Units per kilogram (IU/kg).
Time frame: Up to 5.8 years
Number of Participants Who Achieved Transfusion-free Maintenance of Hemoglobin Levels
Transfusion free maintenance of hemoglobin levels during prophylactic treatment with rVWF (vonicog alfa) were reported.
Time frame: Up to 5.8 years
Change From Baseline in Ferritin Levels Over Time
Change from baseline in ferritin levels over time during prophylactic treatment with rVWF (vonicog alfa) were reported. Baseline Ferritin lab assay for rollover participants in cohorts 1, 2 and 3 were not mandatory per protocol at the Screening Visit of this study as the results from End of Study (EOS) visit of parent studies were expected to be utilized for rollover cohorts 1-3. However, many participants in cohort 1 did not have this data collected at EOS Visit of parent study 071301 and no participant in cohorts 2 and 3 had this data collected at EOS Visit of parent studies 071301 and 071102.
Time frame: Up to 5.8 years
Overall Hemostatic Efficacy Rating
Overall Hemostatic Efficacy Rating at resolution of bleed with respect to treatment of BEs for initial 12 months of study in OD cohorts. Hemostatic efficacy for treatment of BEs was rated on 4-point Likert scale as:excellent=full relief of pain\&cessation of objective signs of bleeding after single infusion,no additional infusion is required for control of bleeding\&administration of further infusion to maintain hemostasis would not affect scoring;good=definite pain relief\&/or improvement in signs of bleeding after single infusion,possibly requires \>2 infusions for complete resolution\&administration of further infusion to maintain hemostasis would not affect scoring;fair=probable\&/or slight relief of pain\&slight improvement in signs of bleeding after single infusion,required multiple infusions for complete resolution;none=no improvement of signs/symptoms or conditions worsen.Missing=number of unique BEs without any overall hemostatic efficacy rating at resolution of breakthrough BE.
Time frame: Initial 12 months of study
Number of Infusions of Vonicog Alfa
Number of infusions of rVWF (vonicog alfa) utilized to treat BEs during OD treatment while enrolled in the study were reported.
Time frame: Up to 5.8 years
Number of Infusions of ADVATE
Number of infusions of ADVATE (rFVIII, octocog alfa) utilized to treat BEs during OD treatment while enrolled in the study were reported.
Time frame: Up to 5.8 years
Weight-adjusted Consumption of Vonicog Alfa Per Bleeding Episode
Weight-adjusted consumption (IU/kg) was derived as the total units infused (IU) divided by the last available body weight (kg) prior to the infusion. Weight-adjusted consumption of rVWF (vonicog alfa) per bleeding episode during OD treatment while enrolled in the study were reported.
Time frame: Up to 5.8 years
Weight-adjusted Consumption of ADVATE Per Bleeding Episode
Weight-adjusted consumption (IU/kg) was derived as the total units infused (IU) divided by the last available body weight (kg) prior to the infusion. Weight-adjusted consumption of ADVATE (rFVIII, octocog alfa) per bleeding episode during OD treatment while enrolled in the study were reported.
Time frame: Up to 5.8 years
Participants took part in the study at 23 investigative sites globally from 1 April 2019 to 30 January 2025.
| Milestone | Cohort 1: Prophylaxis | Cohort 2: Prophylaxis | Cohort 3: Prophylaxis | Cohort 4: Prophylaxis | Cohort 5: On Demand | Cohort 6: On Demand |
|---|---|---|---|---|---|---|
| Started | 10 | 1 | 1 | 5 | 16 | 2 |
| Completed | 10 | 1 | 1 | 3 | 15 | 1 |
| Not completed | 0 | 0 | 0 | 2 | 1 | 1 |
| Withdrew: Physician decision | 0 | 0 | 0 | 1 | 0 | 0 |
| Withdrew: Withdrawal by subject | 0 | 0 | 0 | 0 | 0 | 1 |
| Withdrew: Site closed by sponsor | 0 | 0 | 0 | 1 | 1 | 0 |
sABR was derived as \[number of treated bleeds\] / \[duration in years\]. Bleeds with unknown causality were considered as spontaneous. Bleeds were categorized based on the investigator assessment of cause. sABR during the first 12 months of prophylactic treatment with rVWF (vonicog alfa) was reported.
| spontaneous bleeds per year | Cohort 1: Prophylaxis | Cohort 2: Prophylaxis | Cohort 3: Prophylaxis | Cohort 4: Prophylaxis |
|---|---|---|---|---|
| Spontaneous Annualized Bleeding Rate (sABR) | 1.430 ± 2.3894 | 1.040 ± NA | 0.000 ± NA | 3.022 ± 2.4746 |
An adverse event (AE): any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to medicinal product. TEAE was defined as any AE that started after the first administration of study drug in this continuation study. Serious TEAEs: any untoward medical occurrence that: 1) results in death, 2) is life-threatening, 3) requires inpatient hospitalization or prolongation of existing hospitalization, 4) results in persistent or significant disability/incapacity, 5) leads to a congenital anomaly/birth defect in the offspring of the participant or 6) is medically important.
| Participants | Cohort 1: Prophylaxis | Cohort 2: Prophylaxis | Cohort 3: Prophylaxis | Cohort 4: Prophylaxis | Cohort 5: On Demand | Cohort 6: On Demand |
|---|---|---|---|---|---|---|
| TEAEs | 8 | 1 | 1 | 4 | 15 | 2 |
| Serious TEAEs | 3 | 0 | 0 | 1 | 3 | 1 |
An AE is defined as any untoward medical occurrence in a participant administered IP that does not necessarily have a causal relationship with the treatment. TEAE was defined as any AE that started after the first administration of study drug in this continuation study. Severity of TEAEs was determined by following definitions: Mild: No limitation of usual activities; Moderate: Some limitation of usual activities and may required therapeutic intervention; Severe: Inability to carry out usual activities with sequelae, which required therapeutic intervention. Number of participants with TEAEs based on severity of TEAEs were reported.
| Participants | Cohort 1: Prophylaxis | Cohort 2: Prophylaxis | Cohort 3: Prophylaxis | Cohort 4: Prophylaxis | Cohort 5: On Demand | Cohort 6: On Demand |
|---|---|---|---|---|---|---|
| Mild | 7 | 1 | 1 | 4 | 14 | 2 |
| Moderate | 7 | 0 | 0 | 3 | 11 | 1 |
| Severe | 3 | 0 | 0 | 1 | 1 | 2 |
An AE is defined as any untoward medical occurrence in a participant administered IP that does not necessarily have a causal relationship with the treatment. TEAE was defined as any AE that started after the first administration of study drug in this continuation study. A physician/investigator made the assessment of relationship to investigational product for each AE. Number of participants with TEAEs based on causality were reported.
| Participants | Cohort 1: Prophylaxis | Cohort 2: Prophylaxis | Cohort 3: Prophylaxis | Cohort 4: Prophylaxis | Cohort 5: On Demand | Cohort 6: On Demand |
|---|---|---|---|---|---|---|
| Number of Participants Based on Causality of TEAEs | 0 | 0 | 0 | 0 | 0 | 0 |
Thromboembolism defined as formation of a clot (thrombus) in a blood vessel that breaks loose, is carried by the blood stream and could plug another vessel. Number of participants with thromboembolic events as TEAEs of special interest were reported.
| Participants | Cohort 1: Prophylaxis | Cohort 2: Prophylaxis | Cohort 3: Prophylaxis | Cohort 4: Prophylaxis | Cohort 5: On Demand | Cohort 6: On Demand |
|---|---|---|---|---|---|---|
| Number of Participants With Thromboembolic Events | 0 | 0 | 0 | 0 | 0 | 0 |
Hypersensitivity (also called hypersensitivity reaction or intolerance) defined as undesirable reactions produced by the normal immune system, including allergies and autoimmunity. Potential hypersensitivity events were identified by broad search criteria and then medically assessed. Number of participants with hypersensitivity reactions as TEAEs of special interest was calculated.
| Participants | Cohort 1: Prophylaxis | Cohort 2: Prophylaxis | Cohort 3: Prophylaxis | Cohort 4: Prophylaxis | Cohort 5: On Demand | Cohort 6: On Demand |
|---|---|---|---|---|---|---|
| Number of Participants With Hypersensitivity Reactions | 0 | 0 | 0 | 0 | 0 | 0 |
Three functional VWF assays for von Willebrand factor collagen binding (VWF:CB), von Willebrand factor: Ristocetin Cofactor (VWF:RCo) and von Willebrand factor VIII B (VWF:FVIIIB) were used to test the presence of neutralizing anti-VWF antibodies. Neutralizing antibodies to VWF:RCo, VWF:CB and VWF:FVIIIB activities were measured by assays based on the Bethesda assay established for quantitative analysis of FVIII inhibitors (Nijmegen modification of the Bethesda assay). Only confirmed neutralizing anti -VWF antibodies were considered inhibitors. Number of participants who developed neutralizing antibodies to rVWF were assessed.
| Participants | Cohort 1: Prophylaxis | Cohort 2: Prophylaxis | Cohort 3: Prophylaxis | Cohort 4: Prophylaxis | Cohort 5: On Demand | Cohort 6: On Demand |
|---|---|---|---|---|---|---|
| Number of Participants Who Developed Neutralizing Antibodies to Von Willebrand Factor (VWF) | 0 | 0 | 0 | 0 | 0 | 0 |
Three functional VWF assays for von Willebrand factor collagen binding (VWF:CB), von Willebrand factor: Ristocetin Cofactor (VWF:RCo) and von Willebrand factor VIII B (VWF:FVIIIB) were used to test the presence of neutralizing anti-VWF antibodies. Neutralizing antibodies to VWF:RCo, VWF:CB and VWF:FVIIIB activities was measured by assays based on the Bethesda assay established for quantitative analysis of FVIII inhibitors (Nijmegen modification of the Bethesda assay). Only confirmed neutralizing anti -VWF antibodies were considered inhibitors. Number of participants who developed neutralizing antibodies to FVIII were assessed.
| Participants | Cohort 1: Prophylaxis | Cohort 2: Prophylaxis | Cohort 3: Prophylaxis | Cohort 4: Prophylaxis | Cohort 5: On Demand | Cohort 6: On Demand |
|---|---|---|---|---|---|---|
| Number of Participants Who Developed Neutralizing Antibodies to Factor VIII (FVIII) | 0 | 0 | 0 | 0 | 0 | 0 |
The presence of total binding anti-VWF antibodies was determined by an enzyme-linked immunosorbent assay (ELISA) employing polyclonal anti-human Immunoglobulin (Ig) antibodies (IgG, IgM and IgA). Number of participants who developed of total binding antibodies to rVWF were assessed.
| Participants | Cohort 1: Prophylaxis | Cohort 2: Prophylaxis | Cohort 3: Prophylaxis | Cohort 4: Prophylaxis | Cohort 5: On Demand | Cohort 6: On Demand |
|---|---|---|---|---|---|---|
| Number of Participants Who Developed Total Binding Antibodies to Von Willebrand Factor (VWF) | 0 | 0 | 0 | 0 | 0 | 0 |
Binding antibodies against FVIII were analyzed using a proprietary enzyme immunoassay. Number of participants who developed of total binding antibodies to FVIII were assessed.
| Participants | Cohort 1: Prophylaxis | Cohort 2: Prophylaxis | Cohort 3: Prophylaxis | Cohort 4: Prophylaxis | Cohort 5: On Demand | Cohort 6: On Demand |
|---|---|---|---|---|---|---|
| Number of Participants Who Developed Total Binding Antibodies to Factor VIII (FVIII) | 0 | 0 | 0 | 0 | 1 | 0 |
Total Ig antibodies (IgG, IgA, IgM) against CHO protein were analyzed using ELISA. Number of participants who developed binding antibodies to CHO proteins were assessed.
| Participants | Cohort 1: Prophylaxis | Cohort 2: Prophylaxis | Cohort 3: Prophylaxis | Cohort 4: Prophylaxis | Cohort 5: On Demand | Cohort 6: On Demand |
|---|---|---|---|---|---|---|
| Number of Participants Who Developed Binding Antibodies to Chinese Hamster Ovary (CHO) Proteins | 0 | 0 | 0 | 0 | 0 | 0 |
Detection and quantification of IgG antibodies originating from human plasma that were directed against mouse-IgG (HAMA: human anti- mouse antibodies) were assessed using ELISA (Medac, Hamburg, Germany). Number of participants who developed binding antibodies to Mouse IgG were assessed.
| Participants | Cohort 1: Prophylaxis | Cohort 2: Prophylaxis | Cohort 3: Prophylaxis | Cohort 4: Prophylaxis | Cohort 5: On Demand | Cohort 6: On Demand |
|---|---|---|---|---|---|---|
| Number of Participants Who Developed Binding Antibodies to Mouse Immunoglobulin G (IgG) | 0 | 0 | 0 | 0 | 0 | 0 |
Total Ig antibodies (IgG, IgA, IgM) against human furin were analyzed using ELISA. Number of participants who developed binding antibodies to rFurin were assessed.
| Participants | Cohort 1: Prophylaxis | Cohort 2: Prophylaxis | Cohort 3: Prophylaxis | Cohort 4: Prophylaxis | Cohort 5: On Demand | Cohort 6: On Demand |
|---|---|---|---|---|---|---|
| Number of Participants Who Develop Binding Antibodies to Recombinant Furin (rFurin) | 0 | 0 | 0 | 0 | 0 | 0 |
Vital signs included blood pressure (systolic and diastolic), pulse rate, respiratory rate and body temperature. Number of participants with clinically significant change from baseline in vital signs were assessed.
| Participants | Cohort 1: Prophylaxis | Cohort 2: Prophylaxis | Cohort 3: Prophylaxis | Cohort 4: Prophylaxis | Cohort 5: On Demand | Cohort 6: On Demand |
|---|---|---|---|---|---|---|
| Number of Participants With Clinically Significant Changes in Vital Signs | 0 | 0 | 0 | 0 | 0 | 0 |
Clinical laboratory parameters included serum chemistry, hematology and urinalysis assessments. Number of participants with clinically significant change from baseline in clinical laboratory parameters were assessed.
| Participants | Cohort 1: Prophylaxis | Cohort 2: Prophylaxis | Cohort 3: Prophylaxis | Cohort 4: Prophylaxis | Cohort 5: On Demand | Cohort 6: On Demand |
|---|---|---|---|---|---|---|
| Serum Chemistry | 0 | 0 | 0 | 0 | 0 | 0 |
| Hematology | 0 | 0 | 0 | 0 | 0 | 0 |
| Urinalysis | 0 | 0 | 0 | 0 | NA | NA |
sABR was derived as \[number of treated bleeds\] / \[duration in years\]. Bleeds with unknown causality were considered as spontaneous. Bleeds were categorized based on the investigator assessment of cause. sABR during prophylaxis treatment with rVWF (vonicog alfa) while enrolled in the study were reported.
| spontaneous bleeds per year | Cohort 1: Prophylaxis | Cohort 2: Prophylaxis | Cohort 3: Prophylaxis | Cohort 4: Prophylaxis |
|---|---|---|---|---|
| Spontaneous Annualized Bleeding Rate (sABR) Under Prophylactic Treatment | 1.122 ± 2.1084 | 0.330 ± NA | 0.000 ± NA | 2.110 ± 1.9954 |
Categorized as ≥ 0 to \< 1 infusion per week, ≥ 1 to \< 2 infusions per week, ≥ 2 to \< 3 infusions per week, ≥ 3 infusions per week. The number of participants categorized based on number of infusions per week during prophylactic treatment with rVWF (vonicog alfa) were reported.
| Participants | Cohort 1: Prophylaxis | Cohort 2: Prophylaxis | Cohort 3: Prophylaxis | Cohort 4: Prophylaxis |
|---|---|---|---|---|
| ≥0 to <1 | 1 (0 to —) | 0 | 0 | 0 |
| ≥ 1to <2 | 6 (60.0 to —) | 1 | 1 | 5 |
| ≥2 to <3 | 3 (40.0 to —) | 0 | 0 | 0 |
| ≥3 | 0 (0 to —) | 0 | 0 | 0 |
The sABR was the number of spontaneous bleeds divided by the observation period in years, where an observation period = (date of completion/termination-date of first dose+1)/365.2425. sABR was categorized based on number of BEs as 0, greater than (\>) 0 through 2, \>2 through 5, \>5 during the prophylactic treatment with rVWF (vonicog alfa). Bleeding at multiple locations related to the same injury was counted as single BE. BEs of unknown cause were counted as spontaneous bleeds. Number of participants categorized based on sABR during prophylactic treatment with rVWF (vonicog alfa) were reported.
| Participants | Cohort 1: Prophylaxis | Cohort 2: Prophylaxis | Cohort 3: Prophylaxis | Cohort 4: Prophylaxis |
|---|---|---|---|---|
| 0 bleeds/year | 5 | 0 | 1 | 0 |
| >0 to ≤2 bleeds/year | 3 | 1 | 0 | 3 |
| >2 to ≤5 bleeds/year | 1 | 0 | 0 | 1 |
| >5 bleeds/year | 1 | 0 | 0 | 1 |
Time to event estimates and confidence intervals obtained from Kaplan-Meier analysis. Participants with 0 bleeds during each study period were censored at the date of the last day in that study period.
| days | Cohort 1: Prophylaxis | Cohort 2: Prophylaxis | Cohort 3: Prophylaxis | Cohort 4: Prophylaxis |
|---|---|---|---|---|
| Time to First Bleeding Event on Prophylaxis Treatment | 172 (5 to NA) | 141 (NA to NA) | NA (NA to NA) | 88 (9 to NA) |
sABR was derived as \[number of treated bleeds\] / \[duration in years\]. sABR for BEs based on location of bleeding: Skin, Muscle, Mucosal Nasal, Mucosal Oral, Joint, Gastrointestinal (GI), Menstrual/Heavy Menstrual, Venipuncture Site, Soft Tissue, Body Cavity, Hematuria, Central Nervous System (CNS) and Other, while on prophylactic treatment with rVWF (vonicog alfa) were reported.
| bleeds per year | Cohort 1: Prophylaxis | Cohort 2: Prophylaxis | Cohort 3: Prophylaxis | Cohort 4: Prophylaxis |
|---|---|---|---|---|
| Skin | 0.033 ± 0.1044 | 0.000 ± NA | 0.000 ± NA | 0.000 ± 0.0000 |
| Muscle | 0.000 ± 0.0000 | 0.000 ± NA | 0.000 ± NA | 0.068 ± 0.1521 |
| Mucosal, Nasal | 0.199 ± 0.3542 | 0.000 ± NA | 0.000 ± NA | 0.068 ± 0.1521 |
| Mucosal, Oral | 0.268 ± 0.7358 | 0.330 ± NA | 0.000 ± NA | 0.268 ± 0.5993 |
| Joint | 0.067 ± 0.2119 | 0.000 ± NA | 0.000 ± NA | 1.370 ± 2.3644 |
| GI | 0.000 ± 0.0000 | 0.000 ± NA | 0.000 ± NA | 0.136 ± 0.3041 |
| Menstrual/Heavy Menstrual | 2.770 ± 3.9174 | 0.000 ± NA | — | 0.500 ± 0.7071 |
| Venipuncture Site | 0.000 ± 0.0000 | 0.000 ± NA | 0.000 ± NA | 0.000 ± 0.0000 |
| Soft Tissue | 0.000 ± 0.0000 | 0.000 ± NA | 0.000 ± NA | 0.000 ± 0.0000 |
| Body Cavity | 0.000 ± 0.0000 | 0.000 ± NA | 0.000 ± NA | 0.000 ± 0.0000 |
| Hematuria | 0.000 ± 0.0000 | 0.000 ± NA | 0.000 ± NA | 0.000 ± 0.0000 |
| CNS | 0.000 ± 0.0000 | 0.000 ± NA | 0.000 ± NA | 0.000 ± 0.0000 |
| Other | 0.067 ± 0.1413 | 0.000 ± NA | 0.000 ± NA | 0.068 ± 0.1521 |
Total number of infusions during prophylactic treatment with rVWF (vonicog alfa) were reported.
| infusions | Cohort 1: Prophylaxis | Cohort 2: Prophylaxis | Cohort 3: Prophylaxis | Cohort 4: Prophylaxis |
|---|---|---|---|---|
| Total Number of Infusions During Prophylactic Treatment | 287.8 ± 53.42 | 157.0 ± NA | 177.0 ± NA | 159.2 ± 41.55 |
Average number of infusions per week during prophylactic treatment with rVWF (vonicog alfa) were reported.
| infusions per week | Cohort 1: Prophylaxis | Cohort 2: Prophylaxis | Cohort 3: Prophylaxis | Cohort 4: Prophylaxis |
|---|---|---|---|---|
| Average Number of Infusions Per Week During Prophylactic Treatment | 1.87 ± 0.351 | 1.01 ± NA | 1.14 ± NA | 1.38 ± 0.372 |
For each participant, the body weight-adjusted dose (IU/kg) was derived as the number of units of rVWF infused (IU) divided by the last available body weight (kilogram \[kg\]) prior to the infusion. Total weight adjusted consumption of rVWF (vonicog alfa) per participant during prophylactic treatment with rVWF (vonicog alfa) was reported as International Units per kilogram (IU/kg).
| IU/kg | Cohort 1: Prophylaxis | Cohort 2: Prophylaxis | Cohort 3: Prophylaxis | Cohort 4: Prophylaxis |
|---|---|---|---|---|
| Total Weight Adjusted Consumption of Recombinant Von Willebrand Factor (rVWF) (Vonicog Alfa) Per Participant During Prophylactic Treatment | 14953.497 ± 3349.4461 | 9992.460 ± NA | 9270.620 ± NA | 9171.746 ± 1505.5667 |
Transfusion free maintenance of hemoglobin levels during prophylactic treatment with rVWF (vonicog alfa) were reported.
| Participants | Cohort 1: Prophylaxis | Cohort 2: Prophylaxis | Cohort 3: Prophylaxis | Cohort 4: Prophylaxis |
|---|---|---|---|---|
| Number of Participants Who Achieved Transfusion-free Maintenance of Hemoglobin Levels | 8 | 1 | 1 | 5 |
Change from baseline in ferritin levels over time during prophylactic treatment with rVWF (vonicog alfa) were reported. Baseline Ferritin lab assay for rollover participants in cohorts 1, 2 and 3 were not mandatory per protocol at the Screening Visit of this study as the results from End of Study (EOS) visit of parent studies were expected to be utilized for rollover cohorts 1-3. However, many participants in cohort 1 did not have this data collected at EOS Visit of parent study 071301 and no participant in cohorts 2 and 3 had this data collected at EOS Visit of parent studies 071301 and 071102.
| picomole per liter (pmol/L) | Cohort 1: Prophylaxis | Cohort 2: Prophylaxis | Cohort 3: Prophylaxis | Cohort 4: Prophylaxis |
|---|---|---|---|---|
| Baseline | 148.5 ± 171.83 | — | — | 90.8 ± 110.82 |
| Month 1 | 11.0 ± 18.38 | — | — | -31.0 ± 44.89 |
| Month 2 | 0.0 ± 1.41 | — | — | -43.8 ± 59.60 |
| Month 3 | -18.5 ± 21.92 | — | — | -33.3 ± 64.57 |
| Month 6 | 2.0 ± 2.83 | — | — | -16.6 ± 19.88 |
| Month 9 | 58.5 ± 91.22 | — | — | -12.8 ± 53.05 |
| Month 12 | 19.0 ± 26.87 | — | — | -27.0 ± 27.51 |
| Month 15 | 5.5 ± 13.44 | — | — | -25.7 ± 80.16 |
| Month 18 | 18.0 ± 46.67 | — | — | -49.7 ± 52.56 |
| Month 21 | 37.5 ± 64.35 | — | — | -59.3 ± 50.16 |
| Month 24 | 12.0 ± 26.87 | — | — | -53.3 ± 91.22 |
| Month 27 | 34.0 ± 60.81 | — | — | -54.0 ± 55.56 |
| Month 30 | 46.5 ± 77.07 | — | — | -70.7 ± 70.12 |
| Month 33 | 71.5 ± 106.77 | — | — | -21.3 ± 114.00 |
| End of Study | 38.5 ± 48.79 | — | — | -27.6 ± 52.46 |
Overall Hemostatic Efficacy Rating at resolution of bleed with respect to treatment of BEs for initial 12 months of study in OD cohorts. Hemostatic efficacy for treatment of BEs was rated on 4-point Likert scale as:excellent=full relief of pain\&cessation of objective signs of bleeding after single infusion,no additional infusion is required for control of bleeding\&administration of further infusion to maintain hemostasis would not affect scoring;good=definite pain relief\&/or improvement in signs of bleeding after single infusion,possibly requires \>2 infusions for complete resolution\&administration of further infusion to maintain hemostasis would not affect scoring;fair=probable\&/or slight relief of pain\&slight improvement in signs of bleeding after single infusion,required multiple infusions for complete resolution;none=no improvement of signs/symptoms or conditions worsen.Missing=number of unique BEs without any overall hemostatic efficacy rating at resolution of breakthrough BE.
| bleeding episodes | Cohort 5: On Demand | Cohort 6: On Demand |
|---|---|---|
| Excellent | 74 | 21 |
| Good | 1 | 0 |
| Fair | 0 | 0 |
| None | 0 | 0 |
| Missing | 1 | 3 |
Number of infusions of rVWF (vonicog alfa) utilized to treat BEs during OD treatment while enrolled in the study were reported.
| infusions | Cohort 5: On Demand | Cohort 6: On Demand |
|---|---|---|
| Number of Infusions of Vonicog Alfa | 1.1 ± 0.65 | 1.2 ± 0.45 |
Number of infusions of ADVATE (rFVIII, octocog alfa) utilized to treat BEs during OD treatment while enrolled in the study were reported.
| infusions | Cohort 5: On Demand | Cohort 6: On Demand |
|---|---|---|
| Number of Infusions of ADVATE | 1.1 ± 0.25 | 1.0 ± 0.00 |
Weight-adjusted consumption (IU/kg) was derived as the total units infused (IU) divided by the last available body weight (kg) prior to the infusion. Weight-adjusted consumption of rVWF (vonicog alfa) per bleeding episode during OD treatment while enrolled in the study were reported.
| IU/kg per bleeding episode | Cohort 5: On Demand | Cohort 6: On Demand |
|---|---|---|
| Weight-adjusted Consumption of Vonicog Alfa Per Bleeding Episode | 56.109 ± 33.1312 | 61.713 ± 26.6936 |
Weight-adjusted consumption (IU/kg) was derived as the total units infused (IU) divided by the last available body weight (kg) prior to the infusion. Weight-adjusted consumption of ADVATE (rFVIII, octocog alfa) per bleeding episode during OD treatment while enrolled in the study were reported.
| IU/kg per bleeding episode | Cohort 5: On Demand | Cohort 6: On Demand |
|---|---|---|
| Weight-adjusted Consumption of ADVATE Per Bleeding Episode | 39.217 ± 11.0752 | 35.175 ± 2.2274 |
Collected over Up to 5.8 years. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Cohort 1: Prophylaxis: Adult ≥18 Years | 0/10 (0%) | 3/10 (30%) | 8/10 (80%) |
| Cohort 2: Prophylaxis: Adult ≥18 Years | 0/1 (0%) | 0/1 (0%) | 1/1 (100%) |
| Cohort 3: Prophylaxis: Pediatric 12 to <18 Years | 0/1 (0%) | 0/1 (0%) | 1/1 (100%) |
| Cohort 4: Prophylaxis: Pediatric 12 to <18 Years | 0/2 (0%) | 0/2 (0%) | 2/2 (100%) |
| Cohort 4: Prophylaxis: Adult ≥18 Years | 0/3 (0%) | 1/3 (33.3%) | 2/3 (66.7%) |
| Cohort 5: On Demand: Pediatric <6 Years | 0/3 (0%) | 2/3 (66.7%) | 3/3 (100%) |
| Cohort 5: On Demand: Pediatric 6 to <12 Years | 0/5 (0%) | 1/5 (20%) | 5/5 (100%) |
| Cohort 5: On Demand: Pediatric 12 to <18 Years | 0/6 (0%) | 0/6 (0%) | 6/6 (100%) |
| Cohort 5: On Demand: Adult ≥18 Years | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) |
| Cohort 6: On Demand: Adult ≥18 Years | 0/2 (0%) | 1/2 (50%) | 2/2 (100%) |
| Event | Cohort 1: Prophylaxis: Adult ≥18 Years | Cohort 2: Prophylaxis: Adult ≥18 Years | Cohort 3: Prophylaxis: Pediatric 12 to <18 Years | Cohort 4: Prophylaxis: Pediatric 12 to <18 Years | Cohort 4: Prophylaxis: Adult ≥18 Years | Cohort 5: On Demand: Pediatric <6 Years | Cohort 5: On Demand: Pediatric 6 to <12 Years | Cohort 5: On Demand: Pediatric 12 to <18 Years | Cohort 5: On Demand: Adult ≥18 Years | Cohort 6: On Demand: Adult ≥18 Years |
|---|---|---|---|---|---|---|---|---|---|---|
| Ovarian cyst rupturedReproductive system and breast disorders | 0/10 | 0/1 | 0/1 | 0/2 | 0/3 | 0/3 | 0/5 | 0/6 | 0/2 | 1/2 |
| Coronavirus infectionInfections and infestations | 0/10 | 0/1 | 0/1 | 0/2 | 0/3 | 1/3 | 0/5 | 0/6 | 0/2 | 0/2 |
| FallInjury, poisoning and procedural complications | 0/10 | 0/1 | 0/1 | 0/2 | 0/3 | 1/3 | 0/5 | 0/6 | 0/2 | 0/2 |
| Fibula fractureInjury, poisoning and procedural complications | 0/10 | 0/1 | 0/1 | 0/2 | 1/3 | 0/3 | 0/5 | 0/6 | 0/2 | 0/2 |
| HypotensionVascular disorders | 0/10 | 0/1 | 0/1 | 0/2 | 0/3 | 1/3 | 0/5 | 0/6 | 0/2 | 0/2 |
| Medical device site extravasationGeneral disorders | 0/10 | 0/1 | 0/1 | 0/2 | 0/3 | 1/3 | 0/5 | 0/6 | 0/2 | 0/2 |
| PneumoniaInfections and infestations | 0/10 | 0/1 | 0/1 | 0/2 | 1/3 | 0/3 | 0/5 | 0/6 | 0/2 | 0/2 |
| Tibia fractureInjury, poisoning and procedural complications | 0/10 | 0/1 | 0/1 | 0/2 | 1/3 | 0/3 | 0/5 | 0/6 | 0/2 | 0/2 |
| Spinal compression fractureInjury, poisoning and procedural complications | 0/10 | 0/1 | 0/1 | 0/2 | 0/3 | 0/3 | 1/5 | 0/6 | 0/2 | 0/2 |
| AnaemiaBlood and lymphatic system disorders | 1/10 | 0/1 | 0/1 | 0/2 | 0/3 | 0/3 | 0/5 | 0/6 | 0/2 | 0/2 |
| Event | Cohort 1: Prophylaxis: Adult ≥18 Years | Cohort 2: Prophylaxis: Adult ≥18 Years | Cohort 3: Prophylaxis: Pediatric 12 to <18 Years | Cohort 4: Prophylaxis: Pediatric 12 to <18 Years | Cohort 4: Prophylaxis: Adult ≥18 Years | Cohort 5: On Demand: Pediatric <6 Years | Cohort 5: On Demand: Pediatric 6 to <12 Years | Cohort 5: On Demand: Pediatric 12 to <18 Years | Cohort 5: On Demand: Adult ≥18 Years | Cohort 6: On Demand: Adult ≥18 Years |
|---|---|---|---|---|---|---|---|---|---|---|
| Abdominal painGastrointestinal disorders | 1/10 | 1/1 | 0/1 | 1/2 | 0/3 | 1/3 | 0/5 | 0/6 | 0/2 | 0/2 |
| Angular cheilitisGastrointestinal disorders | 0/10 | 1/1 | 0/1 | 0/2 | 0/3 | 0/3 | 0/5 | 0/6 | 0/2 | 0/2 |
| COVID-19Infections and infestations | 1/10 | 0/1 | 1/1 | 0/2 | 2/3 | 3/3 | 1/5 | 3/6 | 1/2 | 0/2 |
| Chest discomfortGeneral disorders | 0/10 | 0/1 | 1/1 | 0/2 | 0/3 | 0/3 | 0/5 | 0/6 | 0/2 | 0/2 |
| GastroenteritisInfections and infestations | 0/10 | 1/1 | 0/1 | 0/2 | 0/3 | 0/3 | 0/5 | 1/6 | 0/2 | 0/2 |
| HeadacheNervous system disorders | 3/10 | 1/1 | 0/1 | 2/2 | 0/3 | 0/3 | 1/5 | 0/6 | 1/2 | 0/2 |
| Infusion site rashGeneral disorders | 0/10 | 0/1 | 1/1 | 0/2 | 0/3 | 0/3 | 0/5 | 0/6 | 0/2 | 0/2 |
| Irritable bowel syndromeGastrointestinal disorders | 0/10 | 0/1 | 1/1 | 0/2 | 0/3 | 0/3 | 0/5 | 0/6 | 0/2 | 0/2 |
| Muscle spasmsMusculoskeletal and connective tissue disorders | 0/10 | 1/1 | 0/1 | 1/2 | 1/3 | 0/3 | 0/5 | 0/6 | 0/2 | 0/2 |
| NasopharyngitisInfections and infestations | 0/10 | 1/1 | 0/1 | 1/2 | 0/3 | 0/3 | 0/5 | 0/6 | 0/2 | 0/2 |
The Full Analysis Set (FAS) consisted of all participants who satisfied all entry criteria and received any amount of study drug.
| Age, Customized(Participants) | Cohort 1: Prophylaxis | Cohort 2: Prophylaxis | Cohort 3: Prophylaxis | Cohort 4: Prophylaxis | Cohort 5: On Demand | Cohort 6: On Demand | Total |
|---|---|---|---|---|---|---|---|
| <6 years | 0 | 0 | 0 | 0 | 3 | 0 | 3 |
| >=6 to <12 years | 0 | 0 | 0 | 0 | 5 | 0 | 5 |
| >=12 to <18 years | 0 | 0 | 1 | 2 | 6 | 0 | 9 |
| >=18 years | 10 | 1 | 0 | 3 | 2 | 2 | 18 |
| Sex: Female, Male(Participants) | Cohort 1: Prophylaxis | Cohort 2: Prophylaxis | Cohort 3: Prophylaxis | Cohort 4: Prophylaxis | Cohort 5: On Demand | Cohort 6: On Demand | Total |
|---|---|---|---|---|---|---|---|
| Female | 4 | 1 | 0 | 2 | 9 | 1 | 17 |
| Male | 6 | 0 | 1 | 3 | 7 | 1 | 18 |
| Ethnicity (NIH/OMB)(Participants) | Cohort 1: Prophylaxis | Cohort 2: Prophylaxis | Cohort 3: Prophylaxis | Cohort 4: Prophylaxis | Cohort 5: On Demand | Cohort 6: On Demand | Total |
|---|---|---|---|---|---|---|---|
| Hispanic or Latino | 1 | 0 | 0 | 0 | 1 | 0 | 2 |
| Not Hispanic or Latino | 8 | 0 | 1 | 5 | 14 | 2 | 30 |
| Unknown or Not Reported | 1 | 1 | 0 | 0 | 1 | 0 | 3 |
| Race (NIH/OMB)(Participants) | Cohort 1: Prophylaxis | Cohort 2: Prophylaxis | Cohort 3: Prophylaxis | Cohort 4: Prophylaxis | Cohort 5: On Demand | Cohort 6: On Demand | Total |
|---|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| White | 9 | 0 | 1 | 4 | 14 | 2 | 30 |
| More than one race | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
| Unknown or Not Reported | 1 | 1 | 0 | 1 | 1 | 0 | 4 |
PDFs hosted by the registry, ClinicalTrials.gov.
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, Statistical analysis plan, Informed consent form, Clinical study report
Access criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/ For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
Data sharing details ↗ · vivli.org
Ran from Apr 2019 to primary completion in Jan 2025, 69 months.
Results were first posted in Sep 2025, 7 months after primary completion.
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Studies of the drug tested here: Vonicog alfa