What is the mechanism of action of this treatment?

Complement inhibitors, such as those targeting complement protein C5, play a crucial role in the treatment of Atypical Hemolytic Uremic Syndrome (aHUS). These treatments work by blocking the activity of specific proteins in the complement system, preventing the formation of the membrane attack complex (MAC). This inhibition reduces endothelial damage and thrombotic microangiopathy, which are central to the pathophysiology of aHUS. For patients, this means a direct reduction in disease-related complications, potentially leading to better health outcomes and quality of life.

What side effects are associated with this type of intervention?

Common treatments for Atypical Hemolytic Uremic Syndrome (aHUS) that inhibit complement protein C5, such as eculizumab and ravulizumab, often have side effects including increased risk of infections, particularly meningococcal infections, due to the suppression of the complement system. Other side effects may include headache, hypertension, diarrhea, nausea, and upper respiratory tract infections. It is crucial for patients to receive appropriate vaccinations and prophylactic antibiotics to mitigate the risk of severe infections.

What prior FDA approvals exist?

The FDA has approved Eculizumab (Soliris) in 2011 and Ravulizumab (Ultomiris) in 2019 for the treatment of Atypical Hemolytic Uremic Syndrome (aHUS). Both drugs inhibit complement protein C5, similar to Crovalimab, and have demonstrated efficacy in reducing hemolysis, thrombosis, and kidney damage associated with aHUS.

What other types of research exist?

Promising novel alternatives to Crovalimab for aHUS patients include other complement inhibitors such as Ravulizumab (an extended-interval C5 inhibitor) and LNP023 (an oral factor B inhibitor). These therapies are being investigated for their efficacy and safety in managing aHUS by targeting the complement system, similar to Crovalimab.

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Monoclonal Antibodies

Crovalimab for Atypical Hemolytic Uremic Syndrome (COMMUTE-a Trial)

Phase 3

Recruiting

Research Sponsored by Hoffmann-La Roche

Eligibility Criteria Checklist

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

Must have

Clinical evidence of response to a C5 inhibitor (for Switch Cohort only)

Body weight >= 40 kg at screening

Must not have

Recent use of tranexamic acid

Recent intravenous immunoglobulin (IVIg) treatment

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline up to week 25 (after 24 weeks on treatment)

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial aims to test the effectiveness and safety of crovalimab in adults and adolescents with aHUS. Crovalimab helps by calming an overactive immune system that can harm blood vessels and kidneys.

Who is the study for?

Adults and adolescents with atypical Hemolytic Uremic Syndrome (aHUS) who weigh at least 40 kg can join. They must be vaccinated against certain infections, agree to use contraception if applicable, and have a negative pregnancy test for females of childbearing potential. Those with prior kidney transplants due to aHUS or on stable doses of other treatments may also qualify.

What is being tested?

The trial is testing Crovalimab's effectiveness and safety in treating aHUS. It will involve participants who are new to treatment, those switching from other C5 inhibitors, and individuals with specific genetic variations related to the disease.

What are the potential side effects?

While not explicitly listed here, side effects could include reactions similar to other immune therapies such as infusion-related discomfort, increased risk of infections due to immunosuppression, possible allergic reactions, or complications related to the underlying condition.

Eligibility Criteria

Inclusion Criteria

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

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I have shown improvement with a C5 inhibitor treatment.

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I weigh at least 40 kg.

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I am vaccinated against meningitis according to my country's guidelines.

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My TMA is not well-managed after treatment with a C5 inhibitor.

Exclusion Criteria

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

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I have recently taken tranexamic acid.

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I have recently received IVIg treatment.

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

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I haven't been in a drug study or taken experimental therapy in the last 28 days.

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My TMA is not caused by aHUS but by another specific condition.

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I have had kidney disease, but not aHUS.

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I have a condition caused by a reaction to a medication.

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I have or had a condition like cancer, transplant, or autoimmune disease that could cause TMA.

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My kidney disease is not caused by atypical HUS.

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My organs are failing.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline up to week 25 (after 24 weeks on treatment)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline up to week 25 (after 24 weeks on treatment)

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline up to week 25 (after 24 weeks on treatment) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

Mean Change From Baseline in Fatigue (in Adult Participants only)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

1Treatment groups

Experimental Treatment

Group I: CrovalimabExperimental Treatment1 Intervention

Participants will be enrolled in three cohorts: \[1\] Naive Cohort - participants who have not been previously treated with complement inhibitor therapy; \[2\] Switch Cohort - participants who switch to crovalimab from another Complement Component 5 (C5) inhibitor and \[3\] C5 Single Nucleotide Polymorphism (C5 inhibitor) Cohort - participants with documented C5 polymorphism.

0 / 14Eligibility 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

Complement inhibitors, such as those targeting complement protein C5, play a crucial role in the treatment of Atypical Hemolytic Uremic Syndrome (aHUS). These treatments work by blocking the activity of specific proteins in the complement system, preventing the formation of the membrane attack complex (MAC). This inhibition reduces endothelial damage and thrombotic microangiopathy, which are central to the pathophysiology of aHUS. For patients, this means a direct reduction in disease-related complications, potentially leading to better health outcomes and quality of life.