A Study Evaluating the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Crovalimab as Adjunct Treatment in Prevention of Vaso-Occlusive Episodes (VOE) in Sickle Cell Disease (SCD)

Study Overview
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Brief Summary
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This study is designed to evaluate the efficacy, safety and pharmacokinetics of crovalimab compared with placebo as adjunct therapy in the prevention of VOEs in participants with SCD.

Official Title
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A Randomized Double-Blind Phase IIA Study Evaluating the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Crovalimab as Adjunct Treatment in Prevention of Vaso-Occlusive Episodes (VOE) in Sickle Cell Disease (SCD)

Conditions
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Sickle Cell Disease

Intervention / Treatment
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* Drug: Crovalimab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body weight >=40 kg. Male or female with confirmed diagnosis of HbSS (SCD genotype of sickle cell anemia) or HbSβ0 (SCD genotype of sickle cell beta zero thalassemia). Two or more (>=2) to <=10 documented VOEs in the 12 months prior to randomisation. If receiving concurrent SCD-directed therapy, the participant must have been on a stable dose for a minimum of 3 months prior to study enrollment. There should be no plans to modify the participants' dosing throughout the study duration, other than for safety reasons. If receiving erythropoietin, the participant must have been prescribed this medication for the preceding 3 months and be dose-stabilised for at least 3 months prior to study enrollment. Vaccination against N. meningitides serotypes A, C, W, and Y and Vaccinations against H. influenza type B and S. pneumonia. Participants who have been vaccinated (partially or in full) against SARS-CoV-2 with a locally approved vaccine are eligible to be enrolled in the study, 3 days or longer after inoculation. Adequate hepatic and renal function. For women of childbearing potential: agreement to remain abstinent or use contraception during the treatment period and for 10.5 months after the final dose of study treatment. Exclusion Criteria: History of hematopoietic stem cell transplant. Participating in a chronic transfusion program and/or planning on undergoing an exchange transfusion during the duration of the study. History of hypersensitivity, allergic, or anaphylactic reactions to any ingredient contained in the study treatment. Received active treatment on another investigational trial within 28 days (or within five half-lives of that agent, whichever is greater) prior to screening visit, or plans to participate in another investigational drug trial. Hemoglobin <6 g/dL. Known or suspected hereditary complement deficiency. Active systemic bacterial, viral, or fungal infection within 14 days before first drug administration. Presence of fever (>=38 degrees Celsius) within 7 days before the first drug administration. Immunised with a live attenuated vaccine within 1 month before first drug administration. Pregnant or breastfeeding, or intending to become pregnant during the study or within 10.5 months after the final dose of study treatment. Known HIV infection with documented CD4 count <200 cells/microliter within 24 weeks prior to screening. History of N. meningitidis infection within the prior 6 months.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Crovalimab<br>Participants will receive a loading series of Crovalimab comprised of an intravenous (IV) loading dose on Day 1, followed by weekly Crovalimab subcutaneous (SC) doses for 4 weeks on Week 1 Day 2, then on Weeks 2, 3 and 4. Maintenance SC dosing will begin at Week 5 and will continue every 4 weeks (Q4W) thereafter for a total of 48 weeks of treatment. | Drug: Crovalimab<br>* Crovalimab will be administered at a dose of 1000 mg IV (for participants with body weight between 40 kg and 100 kg) or 1500 mg IV (for participants with body weight >= 100 kg) on Week 1 Day 1. On Week 1 Day 2 and on Weeks 2, 3 and 4, crovalimab will be administered at a dose of 340 mg SC. For Week 5 and Q4W thereafter, crovalimab will be administered at a dose of 680 mg SC (for participants with body weight between 40 kg and 100 kg) or 1020 mg SC (for participants with body weight >= 100 kg). Dosing schedule will be as per Arm Description.<br>|
| Placebo Comparator: Placebo<br>Participants will receive matching Placebo administered by IV infusion and SC injection over the same duration as Crovalimab, for a total of 48 weeks of treatment. | Drug: Placebo<br>* Matching Placebo will be administered with the same dosing schedule and equivalent IV and SC volume as weight-based Crovalimab.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized rate of medical facility VOEs (AVR) |  | Baseline up to Week 49 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized rate of home VOE |  | Baseline up to Week 49 | 
| Annualized rate of uncomplicated medical facility VOE |  | Baseline up to Week 49 | 
| Annualized rate of Acute Chest Syndrome (ACS) |  | Baseline to up Week 49 | 
| Annualized rate of days hospitalized for medical facility VOE |  | Baseline up to Week 49 | 
| Annualized rate of days hospitalized for treatment of non-VOE complications of SCD |  | Baseline up to Week 49 | 
| Time to first medical facility VOE from randomization |  | Baseline up to Week 49 | 
| Change in urinary albumin-creatinine ratio |  | Baseline up to Week 49 | 
| Change in Tricuspid Regurgitant Jet Velocity (TRV) |  | Baseline up to Week 49 | 
| Percentage of Participants with TRV >2.5 m/s |  | Week 49 | 
| Change in Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue Score in Adults |  | Baseline up to Week 49 | 
| Percentage of Participants with Adverse Events (AEs) |  | Up to 91 weeks | 
| Serum Concentrations of Crovalimab over time |  | Baseline up to Week 49 | 
| Percentage of Participants with Anti-Drug Antibodies to Crovalimab |  | Baseline up to Week 49 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaso-occlusive episodes, Pain crisis