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).

Sickle Cell Disease Clinical Trial

— CROSSWALK-a  

Official title:

A Phase IB Randomized, Placebo-Controlled Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of Crovalimab for the Management of Acute Uncomplicated Vaso-Occlusive Episodes (VOE) in Patients With Sickle Cell Disease (SCD)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04912869
• Other study ID #: BO42452
• Secondary ID: 2020-004840-27
• Status: Recruiting
• Phase: Phase 1
• Start date: March 26, 2022
• Est. completion date: July 14, 2025

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: BO42452 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: July 14, 2025
• Est. primary completion date: January 14, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 55 Years

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

• 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 >48 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.

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

Drug:
• Crovalimab
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).
• Placebo
Placebo will be administered as a single IV infusion, with an equal volume and over the same duration as weight- based crovalimab

Locations

Country	Name	City	State
Brazil	Hospital das Clinicas - UFRGS	Porto Alegre	RS
Brazil	Hospital Sao Rafael - HSR	Salvador	BA
Brazil	Hospital de Base de Sao Jose do Rio Preto	Sao Jose do Rio Preto	SP
France	CHU Henri Mondor; Service de médecine interne	Créteil
France	Hôpital Saint Eloi; Service de Médecine interne	Montpellier
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
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
United Kingdom	Hammersmith Hospital; Haematology	London
United Kingdom	The Whittington Hospital	London
United Kingdom	Uni. College London Hospital	London
United States	Children'S Healthcare of Atlanta	Atlanta	Georgia
United States	Children's Hospital of Michigan; Pediatrics	Detroit	Michigan
United States	East Carolina University; Brody School of Medicine	Greenville	North Carolina
United States	Icahn School of Medicine at Mount Sinai	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Adverse Events (AEs)		Baseline up to Day 322
Primary	Percentage of Participants with Infusion-Related Reactions and Hypersensitivity		Baseline up to Day 84
Secondary	Time to improvement of the primary acute uncomplicated VOE from Baseline		Baseline up to Day 84
Secondary	Total cumulative opioid dose from Baseline		Baseline up to Day 84
Secondary	Time to discontinuation of all parenteral opioids from baseline		Baseline up to Day 84
Secondary	Time to readiness for hospital discharge from baseline		Baseline up to Day 84
Secondary	Time to hospital discharge from baseline		Baseline up to Day 84
Secondary	Time to a confirmed decrease in pain score of at least 2 points from the maximal pre-dose pain score		Baseline up to Day 84
Secondary	Change in pain score from the maximal pre-dose pain score to the score at hospital discharge		Baseline up to Day 84
Secondary	Percentage of Participants who develop Acute Chest Syndrome (ACS)		Baseline up to Day 28
Secondary	Percentage of Participants requiring intensive care unit (ICU)/critical care admission for SCD-related complications		Baseline up to Day 84
Secondary	Percentage of Participants requiring blood transfusion for SCD-related complications		Baseline up to Day 84
Secondary	Readmission rate for a VOE or VOE-related event within 28 days of discharge of the primary VOE		Baseline up to Day 84
Secondary	Serum Concentrations of Crovalimab over time		Baseline up to Day 84
Secondary	Change in PD biomarkers including complement activity (CH50) over time	Assessed by a Liposome Immunoassay (LIA)	Baseline up to Day 84
Secondary	Change over time in free C5 concentration		Baseline up to Day 84
Secondary	Change over time in soluble complement 5b 9 (sC5b-9) concentration		Baseline up to Day 84
Secondary	Percentage of Participants with Anti-Drug Antibodies to Crovalimab		Baseline up to Day 84