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)

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)

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.

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Drug: Crovalimab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 95
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Rio de Janeiro, Brazil, 20211-030
    • Hemorio
  • São Paulo, Brazil, 01232-010
    • Hospital Samaritano
  • Estado de Bahia
    • Salvador, Estado de Bahia, Brazil, 41253-190
      • Hospital Sao Rafael - HSR
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil
      • Hospital das Clinicas - UFRGS
  • São Paulo
    • Botucatu, São Paulo, Brazil, 18618-970
      • UNESP - Faculdade de Medicina da Universidade Estadual Paulista - Campus Botucatu
    • Ribeirão Preto, São Paulo, Brazil, 14051-140
      • Hospital das Clínicas Faculdades Médicas de Ribeirão Preto
    • São José do Rio Preto, São Paulo, Brazil, 15090-000
      • Hospital de Base de Sao Jose do Rio Preto
    • São Paulo, São Paulo, Brazil, 01323-900
      • Beneficencia Portuguesa de Sao Paulo
• France
  • Créteil, France, 64010
    • Chu Henri Mondor
• Italy
  • Campania
    • Naples, Campania, Italy, 80138
      • Università degli studi della Campania Luigi Vanvitelli
  • Veneto
    • Verona, Veneto, Italy, 37134
      • Azienda Ospedaliera di Verona-Policlinico G.B. Rossi
• Kenya
  • Eldoret, Kenya, 30100
    • International Cancer Institute (ICI)
  • Nairobi, Kenya
    • Gertrude's Children Hospital
• Lebanon
  • Tripoli, Lebanon
    • Hopital Nini
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Amsterdam UMC location VUmc
• South Africa
  • Johannesburg, South Africa, 2193
    • Charlotte Maxeke Johannesburg Hospital
• Spain
  • Madrid, Spain, 28009
    • Hospital General Univ. Gregorio Maranon
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01130
    • Adana Acibadem Hospital; Pediatric Hematology
  • Adana, Turkey (Türkiye), 1330
    • Cukurova University Medical Faculty Balcali Hospital
  • Mersin, Turkey (Türkiye), 33343
    • Mersin Universitesi Tip Fakultesi Hastanesi
• United Kingdom
  • London, United Kingdom, W12 0HS
    • Hammersmith Hospital
  • London, United Kingdom, NW10 7NS
    • Central Middlesex Hospital
• United States
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Children's Hospital of Michigan
  • Mississippi
    • Madison, Mississippi, United States, 39110
      • Mississippi Center for Advanced Medicine
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • East Carolina University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 55 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Crovalimab; 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; 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.
Placebo Comparator: Placebo; 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; Matching Placebo will be administered with the same dosing schedule and equivalent IV and SC volume as weight-based Crovalimab.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2022
• Primary Completion (Actual): June 11, 2025
• Study Completion (Actual): April 9, 2026

Study Registration Dates

• First Submitted: September 20, 2021
• First Submitted That Met QC Criteria: October 8, 2021
• First Posted (Actual): October 13, 2021

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 24, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Vaso-occlusive episodes; Pain crisis
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Anemia, Sickle Cell
• Other Study ID Numbers: BO42451; 2020-004839-25 (EudraCT Number); 2022-502542-28-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No