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).

NCT04912869 | Completed Phase 1 FDA Drug

• 2 other identifiers: BO424522020-004840-27
• Study Type: interventional
• Target: 30
• Locations: 10 countries
• Sites: 16

Brief Summary

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.

Conditions

Sickle Cell Disease

Keywords

Vaso-occlusive episodes; Pain crisis

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Adverse Events (AEs)

  Baseline up to Day 84

• Percentage of Participants with Infusion-Related Reactions and Hypersensitivity

  Baseline up to Day 84

Secondary Outcomes (16)

• 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

Study Arms (2)

Crovalimab

EXPERIMENTAL

Participants will receive a single intravenous (IV) infusion of Crovalimab based on body weight.

Drug: Crovalimab

Placebo

PLACEBO COMPARATOR

Participants will receive a single IV infusion of matching Placebo.

Drug: Placebo

Interventions

Crovalimab DRUG

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).

Crovalimab

Placebo DRUG

Placebo will be administered as a single IV infusion, with an equal volume and over the same duration 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.
• 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 SCD-directed 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.

You may not qualify if:

• 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 \>36 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.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (16)

Children'S Healthcare of Atlanta

Atlanta, Georgia, 30329, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, 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

CHU Henri Mondor

Créteil, 64010, France

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

American University of Beirut - Medical Center

Beirut, 1107 2020, Lebanon

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 Virgen del Rocio

Seville, 41013, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Hammersmith Hospital

London, W12 OHS, 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 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2021
• First Posted: June 3, 2021
• Study Start: March 26, 2022
• Primary Completion: December 23, 2024
• Study Completion: August 15, 2025
• Last Updated: August 26, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

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