What side effects are associated with this type of intervention?

Hydroxyurea, the first-line treatment for SCD, can cause bone marrow suppression, leading to neutropenia, thrombocytopenia, and anemia. Other side effects include gastrointestinal disturbances and potential teratogenicity. Crizanlizumab, used to prevent vaso-occlusive crises, is generally well-tolerated but can cause nausea, arthralgia, and back pain. L-glutamine may lead to constipation, nausea, headache, and abdominal pain. Investigational therapies like crovalimab, which target complement protein C5, are still under study, but similar treatments have been associated with increased risk of infections due to immune modulation.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of sickle cell disease, including hydroxyurea, L-glutamine, voxelotor, and crizanlizumab. Crizanlizumab, a monoclonal antibody, is particularly relevant as it reduces the frequency of vaso-occlusive crises, similar to the investigational drug Crovalimab, which targets the inhibition of Complement Protein C5. These treatments aim to manage and prevent complications associated with sickle cell disease.

What other types of research exist?

Promising novel alternatives to Crovalimab for Sickle Cell Disease patients include crizanlizumab, which targets P-selectin to reduce vaso-occlusive crises, and canakinumab, an IL-1beta inhibitor that has shown reductions in hospitalization and vaso-occlusive episodes. Eculizumab, a complement inhibitor, has also been used successfully in cases of delayed hemolytic transfusion reactions with hyperhemolysis. These alternatives offer different mechanisms of action and may provide additional options for managing SCD.

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Crovalimab for Sickle Cell Disease (CROSSWALK-c Trial)

Phase 2

Waitlist Available

Research Sponsored by Hoffmann-La Roche

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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

Body weight >=40 kg

Must not have

Presence of fever (>=38 degrees Celsius) within 7 days before the first drug administration

Participating in a chronic transfusion program and/or planning on undergoing an exchange transfusion during the duration of the study

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Summary

This trial is testing crovalimab to see if it can safely and effectively prevent painful episodes in people with Sickle Cell Disease by stopping the immune system from causing blood vessel blockages.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects of Crovalimab may include allergic reactions, potential increased risk of infections due to immune system effects, and other unspecified drug-related adverse events.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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I weigh at least 40 kg.

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I have been diagnosed with either sickle cell anemia or sickle cell beta zero thalassemia.

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I am vaccinated against meningitis, Hib, and pneumonia.

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I've been on a stable dose of my current sickle cell disease treatment for at least 3 months.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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I am part of a chronic transfusion program or will have an exchange transfusion during the study.

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I have had a stem cell transplant.

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I have HIV with a CD4 count below 200 in the last 24 weeks.

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I have a genetic issue affecting my immune system.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: CrovalimabExperimental Treatment1 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: PlaceboPlacebo Group1 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.

0 / 10Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Sickle Cell Disease (SCD) include hydroxyurea, red blood cell transfusions, and emerging therapies like Crovalimab. Hydroxyurea works by increasing fetal hemoglobin production, which reduces the sickling of red blood cells and decreases vaso-occlusive episodes. Red blood cell transfusions help by increasing the number of normal red blood cells, thereby reducing anemia and the risk of stroke. Crovalimab, an investigational therapy, inhibits the complement protein C5, which is involved in the inflammatory response and may reduce the frequency of vaso-occlusive episodes. These treatments are crucial for SCD patients as they help manage pain, prevent complications, and improve overall quality of life.

Vaso-occlusive crisis in sickle cell disease: a vicious cycle of secondary events.Transfusional Approach in Multi-Ethnic Sickle Cell Patients: Real-World Practice Data From a Multicenter Survey in Italy.Randomized phase 2 trial of Intravenous Gamma Globulin (IVIG) for the treatment of acute vaso-occlusive crisis in patients with sickle cell disease: Lessons learned from the midpoint analysis.