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) (CROSSWALK-c)

Roche

Status and phase: Active, not recruiting; Phase 2

Conditions: Sickle Cell Disease

Treatments: Drug: Crovalimab; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT05075824

2020-004839-25 (EudraCT Number)

BO42451

2022-502542-28-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

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.

Enrollment: 90 estimated patients

Sex: All

Ages: 12 to 55 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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90 participants in 2 patient groups, including a placebo group

Crovalimab

Experimental group

Description:

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.

Treatment:

Drug: Crovalimab

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo