Crovalimab for Sickle Cell Disease

(CROSSWALK-c Trial)

Not currently recruiting at 52 trial locations

Overseen By Reference Study ID Number: BO42451 https://forpatients.roche.com/

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Hoffmann-La Roche

Disqualifiers: Stem cell transplant, Chronic transfusion, HIV, others

Stay on Your Current Meds You can continue your current medications while participating

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called crovalimab to determine if it can reduce painful episodes in people with sickle cell disease (SCD), a blood disorder that deforms red blood cells and blocks blood flow. The study compares crovalimab to a placebo (a substance with no active treatment) to assess its effectiveness and safety. It targets individuals with sickle cell anemia or a specific type called sickle cell beta zero thalassemia who have experienced between two and ten pain episodes in the past year. Participants should maintain stable doses of any other SCD treatments they are currently taking. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on SCD-directed therapy or erythropoietin, you must have been on a stable dose for at least 3 months before joining the study and should not change the dose during the study unless for safety reasons.

Is there any evidence suggesting that crovalimab is likely to be safe for humans?

Research has shown that crovalimab has been tested for safety in people with sickle cell disease. In earlier studies, patients handled crovalimab well. These studies examined its safety and its ability to reduce pain crises in sickle cell patients.

The treatment has undergone various tests, including a study comparing crovalimab with a placebo (a substance with no active drug). Participants did not report any major safety issues during these tests, suggesting that crovalimab is generally safe. However, it is important to remember that all medications can have side effects.

Overall, crovalimab has shown promise in earlier studies, and the current trial aims to learn more about its safety and effectiveness. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for sickle cell disease?

Unlike the standard treatments for sickle cell disease, like hydroxyurea or blood transfusions, Crovalimab targets a new mechanism by inhibiting the complement system, specifically C5, which is involved in the inflammation process that can lead to pain and other complications in sickle cell patients. This novel approach aims to reduce the frequency of vaso-occlusive crises, which are painful episodes that are a hallmark of the disease. Researchers are excited about Crovalimab because it offers a new way to manage sickle cell disease, potentially providing relief to patients who do not respond well to existing therapies. Additionally, Crovalimab is administered through a combination of IV and subcutaneous injections, which may offer more flexibility and convenience compared to current options.

What evidence suggests that crovalimab might be an effective treatment for sickle cell disease?

Research suggests that crovalimab, which participants in this trial may receive, can help people with sickle cell disease (SCD) by reducing painful episodes known as vaso-occlusive events (VOEs), which occur when blood flow is blocked. Studies have shown that crovalimab blocks a protein responsible for these blockages. Early trials indicated that it is safe and could serve as a helpful additional treatment. While researchers are still gathering full data on its effectiveness in people, its mechanism suggests it could lower the number of VOEs. Participants in this trial may also receive a placebo for comparison. ^{2 3 4 6}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

Adults with Sickle Cell Disease who weigh at least 40 kg, have had 2-10 vaso-occlusive episodes in the past year, and are on a stable dose of current SCD treatments. They must be vaccinated against certain infections and women must agree to use contraception or remain abstinent.

Inclusion Criteria

I have been on a stable dose of erythropoietin for at least 3 months.

I have been vaccinated against COVID-19 with an approved vaccine at least 3 days ago.

I weigh at least 40 kg.

Exclusion Criteria

I have not had a serious infection in the last 14 days.

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

I have had a fever of 38°C or higher in the past week.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Crovalimab or placebo for a total of 48 weeks. Initial loading dose followed by weekly subcutaneous doses for 4 weeks, then maintenance dosing every 4 weeks.

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Crovalimab

Trial Overview The trial is testing Crovalimab's effectiveness as an additional treatment to prevent vaso-occlusive episodes compared to a placebo in people with Sickle Cell Disease.

How Is the Trial Designed?

Group I: Crovalimab Experimental Treatment 1 Intervention

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.

Group II: Placebo Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Citations

1. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/1158/504385/Trials-in-Progress-The-Randomized-Double-Blind

Trials in Progress: The Randomized, Double-Blind, Placebo ... Here, we describe two randomized, double-blind, placebo-controlled trials evaluating crovalimab in pts with SCD: CROSSWALK-a (Phase 1b; NCT04912869) and ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05075824

NCT05075824 | A Study Evaluating the Efficacy, Safety, ... 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 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10112618/

5610823 TRIAL IN PROGRESS A randomized, double-blind, placebo-controlled, Phase 1b study evaluating the safety of crovalimab in managing acute uncomplicated VOEs in pts with SCD.

4. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/blood-disorder/sickle-cell-disease/a-study-evaluating-the-efficacy--safety--pharmacokineti-50959.html

Clinical Trial – Sickle Cell Disease – Efficacy, Safety, ... The purpose of this clinical trial is to compare the effects, good or bad, of crovalimab versus placebo on patients with SCD. In this clinical trial, you will ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05075824

NCT05075824 | A Study Evaluating the Efficacy, Safety, ... This study is designed to evaluate the efficacy, safety and pharmacokinetics of crovalimab compared with placebo as adjunct therapy in the prevention of VOEs ...

6. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/blood-disorder/sickle-cell-disease/a-study-evaluating-the-safety--pharmacokinetics--pharma-03990.html

Clinical Trial – Sickle Cell Disease – Safety, Pharmacoki... You will have a 2 in 3 (67%) chance of being in the crovalimab group and a 1 in 3 (33%) chance of being in the placebo group. During the clinical trial, you can ...