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)

Sickle Cell Disease Clinical Trial

— CROSSWALK-c  

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05075824
• Other study ID #: BO42451
• Secondary ID: 2020-004839-25
• Status: Recruiting
• Phase: Phase 2
• Start date: March 9, 2022
• Est. completion date: January 10, 2025

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: BO42451 https://forpatients.roche.com
• Phone: 888-662-6728 (U.S. and Canada)
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: January 10, 2025
• Est. primary completion date: July 26, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 55 Years

Eligibility

Inclusion Criteria:

• Body weight >=40 kg.
• Male or female with confirmed diagnosis of HbSS (SCD genotype of sickle cell anemia) or HbSß0 (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.

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

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

Locations

Country	Name	City	State
Brazil	UNESP - Faculdade de Medicina da Universidade Estadual Paulista - Campus Botucatu	Botucatu	SP
Brazil	Hospital das Clinicas - UFRGS	Porto Alegre	RS
Brazil	Hospital das Clínicas Faculdades Médicas de Ribeirão Preto	Ribeirao Preto	SP
Brazil	HEMORIO	Rio de Janeiro	RJ
Brazil	Hospital Sao Rafael - HSR	Salvador	BA
Brazil	Hospital de Base de Sao Jose do Rio Preto	Sao Jose do Rio Preto	SP
Brazil	Beneficencia Portuguesa de Sao Paulo	São Paulo	SP
Brazil	Hospital Samaritano	São Paulo	SP
France	CHU Henri Mondor; Service de médecine interne	Créteil
France	Hôpital Saint Eloi; Service de Médecine interne	Montpellier
Italy	Ospedale Galliera; S.S.D. Ematologia	Genova	Liguria
Italy	Università degli Studi della Campania Luigi Vanvitelli; UOC Ematologia ed oncologia pediatrica	Napoli	Campania
Italy	Azienda Ospedaliera di Verona-Policlinico G.B. Rossi; Medicina Interna	Verona	Veneto
Kenya	International Cancer Institute (ICI)	Eldoret
Kenya	Gertrude's Children Hospital; Haematology	Nairobi
Lebanon	Hopital Nini	Tripoli
Netherlands	Amsterdam UMC Location VUMC	Amsterdam
South Africa	Charlotte Maxeke Johannesburg Hospital; Haemophilia Comprehensive Care Center	Johannesburg
Spain	Hospital Universitari Vall d'Hebron; Servicio de Hematologia	Barcelona
Spain	Hospital General Univ. Gregorio Maranon	Madrid
Spain	Hospital Universitario Virgen del Rocio; Servicio de Hematologia	Sevilla
Spain	Hospital Universitario Miguel Servet; Servicio Hematologia	Zaragoza
Turkey	Adana Acibadem Hospital; Pediatric Hematology	Adana
Turkey	Cukurova University Medical Faculty Balcali Hospital	Adana
Turkey	Akdeniz Univesity Medical Faculty	Antalya
Turkey	Dicle University Medical Faculty	Diyarbak?r
Turkey	Mustafa Kemal University Medical Faculty; Infection	Hatay
Turkey	Mersin Universitesi Tip Fakultesi Hastanesi; Tibbi Onkoloji Birimi	Mersin
Turkey	Hacettepe University Medical Faculty Pediatric Hematology	S?hhiye, Ankara
United Kingdom	Central Middlesex Hospital	London
United Kingdom	Hammersmith Hospital	London
United Kingdom	UCL Hospital NHS Trust	London
United States	University of Texas Southwestern Medical Center; Pediatrics	Dallas	Texas
United States	Children's Hospital of Michigan; Pediatrics	Detroit	Michigan
United States	East Carolina University; Brody School of Medicine	Greenville	North Carolina
United States	Mississippi Center for Advanced Medicine	Madison	Mississippi
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	UCSF Benioff Children's Hospital Oakland	Oakland	California

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Brazil,  France,  Italy,  Kenya,  Lebanon,  Netherlands,  South Africa,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annualized rate of medical facility VOEs (AVR)		Baseline up to Week 49
Secondary	Annualized rate of home VOE		Baseline up to Week 49
Secondary	Annualized rate of uncomplicated medical facility VOE		Baseline up to Week 49
Secondary	Annualized rate of Acute Chest Syndrome (ACS)		Baseline to up Week 49
Secondary	Annualized rate of days hospitalized for medical facility VOE		Baseline up to Week 49
Secondary	Annualized rate of days hospitalized for treatment of non-VOE complications of SCD		Baseline up to Week 49
Secondary	Time to first medical facility VOE from randomization		Baseline up to Week 49
Secondary	Change in urinary albumin-creatinine ratio		Baseline up to Week 49
Secondary	Change in Tricuspid Regurgitant Jet Velocity (TRV)		Baseline up to Week 49
Secondary	Percentage of Participants with TRV >2.5 m/s		Week 49
Secondary	Change in Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue Score in Adults		Baseline up to Week 49
Secondary	Percentage of Participants with Adverse Events (AEs)		Up to 91 weeks
Secondary	Serum Concentrations of Crovalimab over time		Baseline up to Week 49
Secondary	Percentage of Participants with Anti-Drug Antibodies to Crovalimab		Baseline up to Week 49