A Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamics and Efficacy of Crovalimab for the Management of Acute Uncomplicated Vaso-Occlusive Episodes (VOE) in Participants With Sickle Cell Disease (SCD).

Study Overview
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Brief Summary
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The purpose of this study is to evaluate crovalimab for the treatment of a sickle cell pain crisis (also known as a VOE) that requires hospitalisation in adult and adolescent participants with SCD. The primary objective of this study is safety and will additionally evaluate pharmacokinetics (how crovalimab is processed by your body), pharmacodynamics (how your body reacts to crovalimab) and the preliminary efficacy of crovalimab compared with placebo.

Official Title
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A Phase IB Randomized, Placebo-Controlled Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of Crovalimab for the Management of Acute Uncomplicated Vaso-Occlusive Episodes (VOE) in Patients With 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. Confirmed diagnosis of HbSS (SCD genotype of sickle cell anemia) or HbSβ0 (SCD genotype of sickle cell beta zero thalassemia). Vaccination against Neisseria Meningitidis serotypes A, C, W, and Y. Vaccinations against H. influenzae type B and S. pneumoniae. Participants vaccinated against SARS-CoV-2 are eligible, as long as it has been 3 days or more after inoculation with the vaccine. Diagnosis of an acute uncomplicated VOE, that requires admission to a hospital/acute medical facility and treatment with parenteral opioid analgesics. Adequate hepatic and renal function. Hemoglobin >=5 grams/deciliter (g/dL) Platelet count >=100,000/microliter (µL) Participants receiving sickle cell therapies must be on a stable dose for >=28 days. For female participants of childbearing potential, an agreement to remain abstinent or use contraception for 322 days (approximately 10.5 months) after the dose of study treatment. Exclusion Criteria: More than 10 VOEs within the last 12 months prior to presentation, that have required a medical facility visit. Pain related to the current VOE ongoing for >48 hours. Acute pain related to avascular necrosis, hepatic or splenic sequestration, or priapism. Pain atypical of an acute uncomplicated VOE. Evidence of or suspicion of ACS. Evidence or high suspicion of a severe systemic infection. Major surgery and/or hospitalization for any reason within 30 days. History of Neisseria meningitidis infection within 6 months prior. Known HIV infection with a documented CD4 count <200 cells/µL. Transfusion or receipt of blood products within 3 months or current participation in a chronic transfusion protocol. Immunized with a live attenuated vaccine within 30 days. History of hematopoietic stem cell transplant. Known or suspected hereditary complement deficiency. Pregnant or breastfeeding, or intending to become pregnant during the study or within 322 days (approximately 10.5 months) after the study drug administration. Participation in another interventional treatment study with an investigational agent or use of any experimental therapy within the prior 28 days or within five half-lives of that investigational product, whichever was greater.

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 single intravenous (IV) infusion of Crovalimab based on body weight. | Drug: Crovalimab<br>* Crovalimab will be administered as a single dose of 1000 milligrams (mg) IV (for participants with a body weight between 40 kilograms (kg) and 100 kg) or 1500 mg IV (for participants with a body weight >=100 kg).<br>|
| Placebo Comparator: Placebo<br>Participants will receive a single IV infusion of matching Placebo. | Drug: Placebo<br>* Placebo will be administered as a single IV infusion, with an equal volume and over the same duration as weight- based crovalimab<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Adverse Events (AEs) |  | Baseline up to Day 322 | 
| Percentage of Participants with Infusion-Related Reactions and Hypersensitivity |  | Baseline up to Day 84 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to improvement of the primary acute uncomplicated VOE from Baseline |  | Baseline up to Day 84 | 
| Total cumulative opioid dose from Baseline |  | Baseline up to Day 84 | 
| Time to discontinuation of all parenteral opioids from baseline |  | Baseline up to Day 84 | 
| Time to readiness for hospital discharge from baseline |  | Baseline up to Day 84 | 
| Time to hospital discharge from baseline |  | Baseline up to Day 84 | 
| Time to a confirmed decrease in pain score of at least 2 points from the maximal pre-dose pain score |  | Baseline up to Day 84 | 
| Change in pain score from the maximal pre-dose pain score to the score at hospital discharge |  | Baseline up to Day 84 | 
| Percentage of Participants who develop Acute Chest Syndrome (ACS) |  | Baseline up to Day 28 | 
| Percentage of Participants requiring intensive care unit (ICU)/critical care admission for SCD-related complications |  | Baseline up to Day 84 | 
| Percentage of Participants requiring blood transfusion for SCD-related complications |  | Baseline up to Day 84 | 
| Readmission rate for a VOE or VOE-related event within 28 days of discharge of the primary VOE |  | Baseline up to Day 84 | 
| Serum Concentrations of Crovalimab over time |  | Baseline up to Day 84 | 
| Change in PD biomarkers including complement activity (CH50) over time | Assessed by a Liposome Immunoassay (LIA) | Baseline up to Day 84 | 
| Change over time in free C5 concentration |  | Baseline up to Day 84 | 
| Change over time in soluble complement 5b 9 (sC5b-9) concentration |  | Baseline up to Day 84 | 
| Percentage of Participants with Anti-Drug Antibodies to Crovalimab |  | Baseline up to Day 84 | 

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