A Phase 2 interventional study of crizanlizumab in Sickle Cell Disease (SCD), sponsored by Novartis Pharmaceuticals. Completed at 12 sites in United States. Open to participants aged 16 Years to 70 Years. Per ClinicalTrials.gov, last updated 2024-10-09.
Sponsored by Novartis Pharmaceuticals (part of Novartis) · Phase 2, Interventional, and Treatment
Among 60 studies in Vaso-Occlusive Crises with a site in United States — 13 open to participants now, 15 under way, 5 of them phase 3. Vaso-Occlusive Crises · United States.
Among the 60 studies in Vaso-Occlusive Crises with a site in United States, this one is the 31st largest by enrollment of the 56 interventional ones that give a count, is the only one that started in 2017, is one of 18 in phase 2, and was the 27th registered.
104 studies on the registry are indexed under Vaso-Occlusive Crises; 31 are open to participants now.
Browse Vaso-Occlusive Crises studies →13 of the 60 studies in Vaso-Occlusive Crises with a site in United States are open now. Recruiting first, the newest first:
University of Maryland, Baltimore · Sites in United States
Mohsen Saidinejad · Sites in United States
CSL Behring · Sites in United States, Belgium, France and 4 more countries
CSL Behring · Sites in United States, Turkey, United Kingdom
Novartis Pharmaceuticals · Sites in United States, Brazil, Colombia and 2 more countries
A study can be open while its sites in United States have not opened yet or have stopped. Only those recruiting at a site in United States →
Of the 17 Vaso-Occlusive Crises studies recruiting now, 7 (41%) set no upper age limit and 6 (35%) stop at 75 or younger; 10 take children under 18; 1 take healthy volunteers.
This study: 16 Years to 70 Years · all sexes · no healthy volunteers.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
60 studies; the count open now beside each. This study's row is marked.
A study in two phases is counted once above. Listed by phase, each with its combined phases: Phase 1 6 · Phase 2 20 · Phase 3 17 · Phase 4 6
First in 2000; this study’s year is marked. 1 started in 2017.
This study's enrollment of 57 is below the median of 81 across 86 interventional studies indexed under Vaso-Occlusive Crises.
Median enrollment 63 across the 56 interventional studies, 82 across the 4 observational. Of the 41 that completed or were terminated, 21 (51%) have results posted.
This tab as a report to print or save as PDF → With an account.
25 of 60 have an industry lead sponsor. The 10 most frequent:
Novartis Pharmaceuticals is the lead sponsor of 2,718 studies on the registry; 221 are open to participants now.
Of its 585 completed or terminated interventional studies of FDA-regulated products, 438 (75%) have results posted.
Novartis Pharmaceuticals has 5 studies filed under Vaso-Occlusive Crises — fewer than ten, so there is no comparison to draw.
3 of the studies in Vaso-Occlusive Crises with a site in United States that are under way reach primary completion within a year, 1 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT06989567Phase 3Asklepion Pharmaceuticals, LLCA Study of Intravenous L-Citrulline in Patients Aged 6-21 Years Old With Sickle Cell Disease Presenting to Emergency Departments in Acute Vaso-Occlusive Crisis | 2027-06 |
| NCT03353584St. Jude Children's Research HospitalEffect of Virtual Reality Technology for Pain Management of Vaso-Occlusive Crisis in Patients With Sickle Cell Disease | 2026-11 |
| NCT06699849CSL BehringSafety, Efficacy, and Pharmacokinetics of CSL889 in Adults and Adolescents With Sickle Cell Disease During Vaso-Occlusive Crisis | 2027-10-22 |
Among the 60 studies in Vaso-Occlusive Crises with a site in United States, from their registry updates:
This tab as a report to print or save as PDF → With an account.
The purpose of the CSEG101A2202 study was to characterize the Pharmacokinetic (PK) and Pharmacodynamic (PD) of SEG101/crizanlizumab and to evaluate the safety and efficacy of SEG101/crizanlizumab in sickle cell disease (SCD) patients.
Study CSEG101A2202 was designed as a Phase II, multicenter, open-label study. The first 45 patients (to identify 27 evaluable patients) were enrolled to the treatment group crizanlizumab 5.0 mg/kg to complete full Pharmacokinetic/Pharmacodynamic (PK/PD) sampling at week 1 and week 15. In all patients, trough PK/PD samples were collected prior to each dose. In addition, throughout the study (and when possible), all patients had blood drawn for serum to assess PK and PD drawn at times of onset and resolution of each VOC event, fever, or infection. Once the up to 45 patients were enrolled, 12 additional patients were enrolled to the exploratory treatment group and began at 7.5 mg/kg of crizanlizumab.
The study was initiated on 19-Dec-2017. This study provides five years follow up data that fully characterizes the safety, tolerability and treatment effect of the 5.0 mg/kg and 7.5 mg/kg doses of crizanlizumab along with the initially planned PK and PD data.
At the time of study closure, crizanlizumab 5.0 mg/kg was an FDA approved treatment in the United States (US) for patients with sickle-cell disease. Therefore, the patients treated with crizanlizumab 5.0 mg/kg dose were encouraged to transition to commercial supply of crizanlizumab. The patients treated with the not currently approved dose of crizanlizumab 7.5 mg/kg were allowed to join a multi-center, multi-national, rollover clinical trial (Study SEG101A2401B), for continued access to treatment with crizanlizumab.
104 studies on the registry are indexed under Vaso-Occlusive Crises; 31 are open to participants now.
This study's enrollment of 57 is below the median of 81 across 86 interventional studies indexed under Vaso-Occlusive Crises.
Browse Vaso-Occlusive Crises studies →Novartis Pharmaceuticals is the lead sponsor of 2,718 studies on the registry; 221 are open to participants now.
Of its 585 completed or terminated interventional studies of FDA-regulated products, 438 (75%) have results posted.
Compared within Vaso-Occlusive Crises, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Anemia, Sickle Cell. The counts are of registry records indexed under each term, refreshed daily. How we classify →
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.
Exclusion Criteria:
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.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
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.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
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 yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
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.
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.
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.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (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.
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.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
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.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
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.
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.
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.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
SEG101 (crizanlizumab) drug at a dose of 5.0 mg/kg (or 7.5 mg/kg for exploratory group) by IV infusion.
Drug: crizanlizumab
Crizanlizumab was administered IV infusion over 30 minutes at the assigned dose on Week 1 Day 1, Week 3 Day 1, and then Day 1 of every 4-week cycle. Cycle = 28 days
Also known as: SEG101
Pharmacokinetic (PK): AUCd15 and AUCtau of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients
To characterize PK of crizanlizumab at 5.0 mg/kg in SCD patients. AUCd15: The AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1) after single dose AUCtau: The AUC calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1)
Time frame: 1st dose: Day 1: (pre-dose, 0.5, 1, 2, 4, 6 & 24 hours post dose, Days 4, 8 & 15; 5th dose: Day 1 (pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post dose), Days 4, 8, 15, 22 & 29
PK: Cmax of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients
To characterize PK of crizanlizumab at 5.0 mg/kg in SCD patients. Cmax: The maximum (peak) observed serum drug concentration after dose administration (mass x volume-1).
Time frame: After the starting dose (Week 1) and after multiple doses (steady state, Week 15)
Pre-dose Concentrations Prior to Each Study Drug Dose
To characterize PK of crizanlizumab at 5.0 mg/kg in SCD patients, by serum concentrations by treatment group. Data was collected prior to each study drug dose; From Week 3 (loading dose), pre-dose (trough) concentrations were obtained every 4 weeks.
Time frame: Pre-dose at Day 1 on Weeks 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, 47, 51
Percentage of P-selectin Inhibition After the Starting Dose (PD-AUCd15), After Multiple Doses (PD-AUCd29) of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients
PD-AUCd15 and PD-AUCd29 were derived from the P-selectin inhibition data of week 1 and week 15, respectively. To characterize PD of crizanlizumab at 5.0 mg/kg in SCD patients The area under the curve (AUC) of percentage of P-selectin inhibition versus time profile after the starting dose (PD-AUCd15) and after multiple doses (PD-AUCd29) is being reported.
Time frame: 1st dose: Day 1: (pre-dose, 0.5, 1, 2, 4, 6 & 24 hours post dose, Days 4, 8, 15; 5th dose: Day 1(pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post dose), Days 4, 8, 15, 22 & 29
Percentage of P-selectin Inhibition Prior to Each Study Drug Dose of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients
To characterize the PD effect of crizanlizumab in terms of Percentage of P-selectin inhibition prior to study drug dose at 5 mg/kg in CSD patients.
Time frame: Pre-dose on Day 1 for Weeks 3, 7, 11, 15, 19, 23, 27, 31,35, 39, 43, 47, 51 (at 0 hr or pre-dose)
Annualized Rate of Vaso-occlusive Crisis (VOC) Events Leading to Healthcare Visit in Clinic/Emergency Room (ER)/Hospital
To assess the efficacy of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in Sickle cell disease (SCD) patients. Annualized rate of VOC=(Number of VOC reported until End date ×365.25)/(End date - date of first dose of study treatment+1). End date is defined as the minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-glutamine or other therapies such as voxelotor and erythropoietin to treat SCD and or to prevent/reduce VOCs, cut-off date).
Time frame: Baseline (Week 1) through approx. 45 months (median exposure to treatment)
Annualized Rate of VOC Events Treated at Home (Based on Documentation by Health Care Provider Following Phone Contact With Patient)
To assess the efficacy of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in SCD patients. Annualized rate of VOC=(Number of VOC reported until End date ×365.25)/(End date - date of first dose of study treatment+1). End date is defined as the minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-glutamine or other therapies such as voxelotor and erythropoietin to treat SCD and or to prevent/reduce VOCs, cut-off date).
Time frame: Baseline (Week 1) through approx. 45 months (median exposure to treatment)
Annualized Rate of Total and VOC-related Hospitalizations and Emergency Room (ER) Visits
To assess the efficacy of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in SCD patients. Annualized rate of hospitalizations and ER visits = number of hospitalizations and ER visits reported until end date × 365.25/(End date - treatment start date + 1). End date is defined as the minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-glutamine or other therapies such as voxelotor and erythropoietin to treat SCD and or to prevent/reduce VOCs, cut-off date).
Time frame: Baseine (Week 1) through approx. 45 months (median exposure to treatment)
Annualized Days of Total and VOC-related Hospitalizations and Emergency Room (ER) Visits
Assess the efficacy of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in SCD patients for hospitalizations and ER visits. Annualized days of all hospitalizations and ER visits = Number of days of all hospitalizations and ER visits × 365.25/(End date - treatment start date + 1). End date is defined as the minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-glutamine or other therapies such as voxelotor and to treat SCD and or to prevent/reduce VOCs, cut-off date).
Time frame: Baseline (Week 1) through approx. 45 months (median exposure to treatment)
Annualized Rate of Each Subcategory of All VOC Events (Acute Chest Syndrome (ACS), Priapism, Uncomplicated Sickle Cell-vaso-occlusive Cisis (Uncomplicated SC-VOCs))
Assess the efficacy of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in SCD patients. The baseline (BL) annualized rate of VOC is defined as the number of VOCs reported in the last 12 months in the eCRF. Annualized rate of VOC=(Number of VOC reported until End date ×365.25)/(End date - date of first dose of study treatment+1). End date is defined as the minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-glutamine or other therapies such as voxelotor and erythropoietin to treat SCD and or to prevent/reduce VOCs, cut-off date).
Time frame: Baseline (Week 1) through approx. 45 months (median exposure to treatment)
Annualized Rate of VOC Events (Including Both Healthcare Visit and Home Treatment)
Assess the efficacy of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in SCD patients. Annualized rate of VOC=(Number of VOC reported until End date ×365.25)/(End date -date of first dose of study treatment+1). End date is defined as th e minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-glutamine or other therapies such as voxelotor and erythropoietin to treat SCD and or to prevent/reduce VOCs, cut-off date).
Time frame: Baseline (Week 1) through approx. 45 months (median exposure to treatment)
Number of Participants With Immunogenicity (IG) by Any Positive Status
Assess safety and tolerability of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in SCD patients by the percentage of participants with any positive status. Immunogenicity is the measurement of anti-drug antibodies (ADA) to crizanlizumab.
Time frame: Baseline (Week 1), post-baseline (approx. 45 months (median exposure))
57 patients were enrolled sequentially to study the at 5 mg/kg arm and at 7.5 mg/kg.
| Milestone | Crizanlizumab 5.0 mg/kg | Crizanlizumab 7.5 mg/kg |
|---|---|---|
| Started | 45 | 12 |
| Completed | 0 | 0 |
| Not completed | 45 | 12 |
| Withdrew: Lost to follow-up | 1 | 0 |
| Withdrew: New therapy for study indication | 1 | 0 |
| Withdrew: Protocol violation | 0 | 1 |
| Withdrew: Patient decision | 13 | 0 |
| Withdrew: Physician decision | 6 | 4 |
| Withdrew: Adverse event | 2 | 1 |
| Withdrew: Death | 1 | 1 |
| Withdrew: Pregnancy | 2 | 0 |
| Withdrew: End of study | 19 | 5 |
To characterize PK of crizanlizumab at 5.0 mg/kg in SCD patients. AUCd15: The AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1) after single dose AUCtau: The AUC calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1)
| hr*μg/mL | Crizanlizumab 5.0 mg/kg |
|---|---|
| Starting dose (Week 1): AUCd15 | 13100 ± 2810 |
| Steady State (Week 15): AUCtau | 20800 ± 5030 |
To characterize PK of crizanlizumab at 5.0 mg/kg in SCD patients. Cmax: The maximum (peak) observed serum drug concentration after dose administration (mass x volume-1).
| μg/mL | Crizanlizumab 5.0 mg/kg |
|---|---|
| Starting dose (Week 1) | 102 ± 29.8 |
| Steady State (Week 15) | 123 ± 36.4 |
To characterize PK of crizanlizumab at 5.0 mg/kg in SCD patients, by serum concentrations by treatment group. Data was collected prior to each study drug dose; From Week 3 (loading dose), pre-dose (trough) concentrations were obtained every 4 weeks.
| μg/mL | Crizanlizumab 5.0 mg/kg |
|---|---|
| Week (W) 3 Day 1 (D)1: 0 hrs pre-dose | 18.0 ± 6.42 |
| W7 D1: 0 hrs pre-dose | 10.8 ± 5.21 |
| W11 D1: 0 hrs pre-dose | 9.04 ± 5.04 |
| W15 D1: 0 hrs pre-dose | 10.0 ± 5.39 |
| W19 D1: 0 hrs pre-dose | 9.37 ± 4.95 |
| W23 D1: 0 hrs pre-dose | 9.91 ± 5.09 |
| W27 D1: 0 hrs pre-dose | 9.65 ± 4.03 |
| W31 D1: 0 hrs pre-dose | 9.75 ± 4.66 |
| W35 D1: 0 hrs pre-dose | 9.48 ± 4.60 |
| W39 D1: 0 hrs pre-dose | 9.54 ± 5.47 |
| W43 D1: 0 hrs pre-dose | 8.53 ± 5.24 |
| W47 D1: 0 hrs pre-dose | 8.96 ± 4.31 |
| W51 D1: 0 hrs pre-dose | 8.45 ± 4.88 |
PD-AUCd15 and PD-AUCd29 were derived from the P-selectin inhibition data of week 1 and week 15, respectively. To characterize PD of crizanlizumab at 5.0 mg/kg in SCD patients The area under the curve (AUC) of percentage of P-selectin inhibition versus time profile after the starting dose (PD-AUCd15) and after multiple doses (PD-AUCd29) is being reported.
| hours*% of P-selectin inhibition | Crizanlizumab 5.0 mg/kg |
|---|---|
| Starting dose (Week 1): PD-AUCd15 | 33200 ± 1830 |
| Steady state (Week 15): PD-AUCd29 | 66900 ± 5540 |
To assess the efficacy of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in Sickle cell disease (SCD) patients. Annualized rate of VOC=(Number of VOC reported until End date ×365.25)/(End date - date of first dose of study treatment+1). End date is defined as the minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-glutamine or other therapies such as voxelotor and erythropoietin to treat SCD and or to prevent/reduce VOCs, cut-off date).
| number of events per year | Crizanlizumab 5.0 mg/kg | Crizanlizumab 7.5 mg/kg |
|---|---|---|
| Baseline annualized rate of VOC | 4.00 (1.0 to 25.0) | 2.00 (1.0 to 9.0) |
| Annualized rate of VOC on treatment | 2.75 (0.0 to 17.3) | 0.97 (0.0 to 7.9) |
To assess the efficacy of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in SCD patients. Annualized rate of VOC=(Number of VOC reported until End date ×365.25)/(End date - date of first dose of study treatment+1). End date is defined as the minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-glutamine or other therapies such as voxelotor and erythropoietin to treat SCD and or to prevent/reduce VOCs, cut-off date).
| number of events per participant-year | Crizanlizumab 5.0 mg/kg | Crizanlizumab 7.5 mg/kg |
|---|---|---|
| Annualized Rate of VOC Events Treated at Home (Based on Documentation by Health Care Provider Following Phone Contact With Patient) | 0.68 (0.21 to 2.17) | 0.71 (0.35 to 1.74) |
To assess the efficacy of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in SCD patients. Annualized rate of hospitalizations and ER visits = number of hospitalizations and ER visits reported until end date × 365.25/(End date - treatment start date + 1). End date is defined as the minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-glutamine or other therapies such as voxelotor and erythropoietin to treat SCD and or to prevent/reduce VOCs, cut-off date).
| number of events per participant-year | Crizanlizumab 5.0 mg/kg | Crizanlizumab 7.5 mg/kg |
|---|---|---|
| Annualized rate (total) | 3.42 (0.0 to 57.8) | 2.47 (0.0 to 8.1) |
| Annualized rate (VOC related) | 3.34 (0.0 to 57.8) | 0.86 (0.0 to 7.9) |
| Hospitalizations/ER Annualized rate (total) | 2.46 (0.0 to 22.1) | 1.44 (0.0 to 7.9) |
| Hospitalizations/ER Annualized rate (VOC related) | 2.27 (0.0 to 22.1) | 0.48 (0.0 to 7.9) |
Assess the efficacy of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in SCD patients for hospitalizations and ER visits. Annualized days of all hospitalizations and ER visits = Number of days of all hospitalizations and ER visits × 365.25/(End date - treatment start date + 1). End date is defined as the minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-glutamine or other therapies such as voxelotor and to treat SCD and or to prevent/reduce VOCs, cut-off date).
| number of days per year | Crizanlizumab 5.0 mg/kg | Crizanlizumab 7.5 mg/kg |
|---|---|---|
| Annualized days (total) | 11.95 (0.0 to 86.2) | 3.17 (0.0 to 36.8) |
| Annualized days (VOC related) | 9.03 (0.0 to 86.2) | 1.57 (0.0 to 36.8) |
| Hospitalizations/ER Annualized days (total) | 10.31 (0.0 to 69.4) | 2.57 (0.0 to 36.8) |
| Hospitalizations/ER Annualized days (VOC related) | 7.27 (0.0 to 69.4) | 0.60 (0.0 to 36.8) |
Assess the efficacy of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in SCD patients. The baseline (BL) annualized rate of VOC is defined as the number of VOCs reported in the last 12 months in the eCRF. Annualized rate of VOC=(Number of VOC reported until End date ×365.25)/(End date - date of first dose of study treatment+1). End date is defined as the minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-glutamine or other therapies such as voxelotor and erythropoietin to treat SCD and or to prevent/reduce VOCs, cut-off date).
| number of events per year | Crizanlizumab 5.0 mg/kg | Crizanlizumab 7.5 mg/kg |
|---|---|---|
| BL annualized rate of VOC: ACS | 0.00 (0.0 to 2.0) | 0.00 (0.0 to 2.0) |
| Annualized rate of VOC on treatment: ACS | 0.62 (0.0 to 2.7) | 0.25 (0.0 to 0.6) |
| BL annualized rate of VOC: Priapism | 1.00 (0.0 to 4.0) | — |
| Annualized rate of VOC on treatment: Priapism | 1.58 (0.0 to 3.8) | — |
| BL annualized rate of VOC: Uncomplicated SC-VOCs | 3.00 (1.0 to 25.0) | 2.00 (1.0 to 9.0) |
| Annualized rate of VOC on treatment: Uncomplicated SC-VOCs | 2.58 (0.0 to 17.3) | 1.04 (0.0 to 7.9) |
Assess the efficacy of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in SCD patients. Annualized rate of VOC=(Number of VOC reported until End date ×365.25)/(End date -date of first dose of study treatment+1). End date is defined as th e minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-glutamine or other therapies such as voxelotor and erythropoietin to treat SCD and or to prevent/reduce VOCs, cut-off date).
| number of events per year | Crizanlizumab 5.0 mg/kg | Crizanlizumab 7.5 mg/kg |
|---|---|---|
| Annualized Rate of VOC Events (Including Both Healthcare Visit and Home Treatment) | 3.42 (0.0 to 17.3) | 1.65 (0.0 to 9.3) |
Assess safety and tolerability of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in SCD patients by the percentage of participants with any positive status. Immunogenicity is the measurement of anti-drug antibodies (ADA) to crizanlizumab.
| Participants | Crizanlizumab 5.0 mg/kg | Crizanlizumab 7.5 mg/kg | All Participants |
|---|---|---|---|
| Baseline: Positive | 0 | 0 | 0 |
| Post-Baseline: Any Positive | 0 | 0 | 0 |
To characterize the PD effect of crizanlizumab in terms of Percentage of P-selectin inhibition prior to study drug dose at 5 mg/kg in CSD patients.
| percentage of P-selectin inhibition | Crizanlizumab 5.0 mg/kg |
|---|---|
| Week (W) 3 Day (D) 1: 0 hrs pre-dose | 97.3 ± 7.49 |
| W7D1: 0 hrs pre-dose | 93.0 ± 17.1 |
| W11D1: 0 hrs pre-dose | 87.8 ± 22.6 |
| W15D1: 0 hrs pre-dose | 94.1 ± 12.8 |
| WD19: 0 hrs pre-dose | 91.7 ± 18.5 |
| W23D1: 0 hrs pre-dose | 93.2 ± 14.9 |
| W27D1: 0 hrs pre-dose | 94.3 ± 13.0 |
| W31D1: 0 hrs pre-dose | 92.4 ± 18.9 |
| W35D1: 0 hrs pre-dose | 91.7 ± 14.7 |
| W39D1: 0 hrs pre-dose | 88.5 ± 21.2 |
| W43D1: 0 hrs pre-dose | 86.1 ± 24.8 |
| W47D1: 0 hrs pre-dose | 92.1 ± 16.8 |
| W51D1: 0 hrs pre-dose | 91.5 ± 17.6 |
Collected over All deaths, Serious Adverse Events, and Other Adverse Events for both 'Treatment phase' and 'Post-treatment follow-up phase' (up to 105 days after the last dose of study treatment) were reported. The median duration of exposure to crizanlizumab was 206.1 weeks in the 5.0 mg/kg dose group and 169.6 weeks in the 7.5 mg/kg dose group.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Crizanlizumab 5.0 mg/kg | 1/45 (2.2%) | 22/45 (48.9%) | 42/45 (93.3%) |
| Crizanlizumab 7.5 mg/kg | 1/12 (8.3%) | 6/12 (50%) | 11/12 (91.7%) |
| All Participants | 2/57 (3.5%) | 28/57 (49.1%) | 53/57 (93%) |
| Event | Crizanlizumab 5.0 mg/kg | Crizanlizumab 7.5 mg/kg | All Participants |
|---|---|---|---|
| AnaemiaBlood and lymphatic system disorders | 0/45 | 1/12 | 1/57 |
| CytopeniaBlood and lymphatic system disorders | 0/45 | 1/12 | 1/57 |
| Cardiac arrestCardiac disorders | 0/45 | 1/12 | 1/57 |
| PyrexiaGeneral disorders | 1/45 | 1/12 | 2/57 |
| CholelithiasisHepatobiliary disorders | 0/45 | 1/12 | 1/57 |
| HypertransaminasaemiaHepatobiliary disorders | 0/45 | 1/12 | 1/57 |
| Ischaemic hepatitisHepatobiliary disorders | 0/45 | 1/12 | 1/57 |
| Anaphylactic reactionImmune system disorders | 0/45 | 1/12 | 1/57 |
| AppendicitisInfections and infestations | 0/45 | 1/12 | 1/57 |
| COVID-19Infections and infestations | 3/45 | 1/12 | 4/57 |
| Event | Crizanlizumab 5.0 mg/kg | Crizanlizumab 7.5 mg/kg | All Participants |
|---|---|---|---|
| PyrexiaGeneral disorders | 13/45 | 3/12 | 16/57 |
| HypokalaemiaMetabolism and nutrition disorders | 12/45 | 2/12 | 14/57 |
| HeadacheNervous system disorders | 12/45 | 2/12 | 14/57 |
| VomitingGastrointestinal disorders | 4/45 | 3/12 | 7/57 |
| Upper respiratory tract infectionInfections and infestations | 10/45 | 2/12 | 12/57 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 8/45 | 2/12 | 10/57 |
| ConstipationGastrointestinal disorders | 3/45 | 2/12 | 5/57 |
| DiarrhoeaGastrointestinal disorders | 4/45 | 2/12 | 6/57 |
| NauseaGastrointestinal disorders | 6/45 | 2/12 | 8/57 |
| Ocular icterusHepatobiliary disorders | 1/45 | 2/12 | 3/57 |
Full Analysis Set (FAS): Consisted of all patients to whom crizanlizumab had been assigned and who received at least 1 dose of study treatment.
| Age, Continuous(years) | Crizanlizumab 5.0 mg/kg | Crizanlizumab 7.5 mg/kg | Total |
|---|---|---|---|
| Mean | 32.3 ± 12.71 | 26.8 ± 12.25 | 31.2 ± 12.71 |
| Age, Customized(participants) | Crizanlizumab 5.0 mg/kg | Crizanlizumab 7.5 mg/kg | Total |
|---|---|---|---|
| 16 - < 18 years | 1 | 2 | 3 |
| 18 - < 65 years | 43 | 10 | 53 |
| 65 - < 70 years | 1 | 0 | 1 |
| Sex: Female, Male(Participants) | Crizanlizumab 5.0 mg/kg | Crizanlizumab 7.5 mg/kg | Total |
|---|---|---|---|
| Female | 25 | 6 | 31 |
| Male | 20 | 6 | 26 |
| Race/Ethnicity, Customized(participants) | Crizanlizumab 5.0 mg/kg | Crizanlizumab 7.5 mg/kg | Total |
|---|---|---|---|
| Black or African American | 44 | 12 | 56 |
| White and Black or African American | 1 | 0 | 1 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Data sharing details ↗ · www.clinicalstudydatarequest.com
Ran from Dec 2017 to primary completion in Jun 2023, 66 months.
Results were first posted in Apr 2024, 9 months after primary completion.
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Studies of the drug tested here: Crizanlizumab