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)

NCT05075824 | Completed Phase 2 FDA Drug

• 3 other identifiers: BO424512020-004839-252022-502542-28-00
• Study Type: interventional
• Target: 95
• Locations: 11 countries
• Sites: 27

Brief Summary

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.

Conditions

Sickle Cell Disease

Keywords

Vaso-occlusive episodes; Pain crisis

Outcome Measures

Primary Outcomes (1)

• Annualized rate of medical facility VOEs (AVR)

  Baseline up to Week 49

Secondary Outcomes (13)

• 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

Study Arms (2)

Crovalimab

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Crovalimab DRUG

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.

Crovalimab

Placebo DRUG

Matching Placebo will be administered with the same dosing schedule and equivalent IV and SC volume as weight-based Crovalimab.

Placebo

Eligibility Criteria

• Age: 12 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (27)

Children's Hospital of Michigan

Detroit, Michigan, 48201, United States

Location

Mississippi Center for Advanced Medicine

Madison, Mississippi, 39110, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

East Carolina University

Greenville, North Carolina, 27834, United States

Location

Hospital Sao Rafael - HSR

Salvador, Estado de Bahia, 41253-190, Brazil

Location

Hospital das Clinicas - UFRGS

Porto Alegre, Rio Grande do Sul, Brazil

Location

UNESP - Faculdade de Medicina da Universidade Estadual Paulista - Campus Botucatu

Botucatu, São Paulo, 18618-970, Brazil

Location

Hospital das Clínicas Faculdades Médicas de Ribeirão Preto

Ribeirão Preto, São Paulo, 14051-140, Brazil

Location

Hospital de Base de Sao Jose do Rio Preto

São José do Rio Preto, São Paulo, 15090-000, Brazil

Location

Beneficencia Portuguesa de Sao Paulo

São Paulo, São Paulo, 01323-900, Brazil

Location

HEMORIO

Rio de Janeiro, 20211-030, Brazil

Location

Hospital Samaritano

São Paulo, 01232-010, Brazil

Location

CHU Henri Mondor

Créteil, 64010, France

Location

Università degli Studi della Campania Luigi Vanvitelli

Naples, Campania, 80138, Italy

Location

Azienda Ospedaliera di Verona-Policlinico G.B. Rossi

Verona, Veneto, 37134, Italy

Location

International Cancer Institute (ICI)

Eldoret, 30100, Kenya

Location

Gertrude's Children Hospital

Nairobi, Kenya

Location

Hopital Nini

Tripoli, Lebanon

Location

Amsterdam UMC Location VUMC

Amsterdam, 1081 HV, Netherlands

Location

Charlotte Maxeke Johannesburg Hospital

Johannesburg, 2193, South Africa

Location

Hospital General Univ. Gregorio Maranon

Madrid, 28009, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Adana Acibadem Hospital; Pediatric Hematology

Adana, 01130, Turkey (Türkiye)

Location

Cukurova University Medical Faculty Balcali Hospital

Adana, 1330, Turkey (Türkiye)

Location

Mersin Universitesi Tip Fakultesi Hastanesi

Mersin, 33343, Turkey (Türkiye)

Location

Central Middlesex Hospital

London, NW10 7NS, United Kingdom

Location

Hammersmith Hospital

London, W12 0HS, United Kingdom

Location

MeSH Terms

Conditions

Anemia, Sickle Cell

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2021
• First Posted: October 13, 2021
• Study Start: March 9, 2022
• Primary Completion: June 11, 2025
• Study Completion: April 9, 2026
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

TU (3); US (4); ZA (1); ES (2); KE (2); NL (1); BR (8); LE (1); FR (1); GB (2); IT (2)