Crovalimab for Atypical Hemolytic Uremic Syndrome

(COMMUTE-p Trial)

Recruiting in Palo Alto (17 mi)

+63 other locations

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Hoffmann-La Roche

Must be taking: C5 inhibitors

Must not be taking: Tranexamic acid, IVIg

Disqualifiers: HIV, Hepatitis B/C, Malignancy, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing crovalimab, a medication that helps control the immune system, in children with a rare disease called aHUS. The goal is to see if it is safe and effective for these patients. Crovalimab works by calming down an overactive part of the immune system to prevent damage to the body. Another similar medication, eculizumab, has been used effectively to treat aHUS by inhibiting the complement system.

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 certain therapies like immunosuppressants or corticosteroids, you must be on a stable dose for at least 28 days before starting the trial.

What data supports the effectiveness of the drug Crovalimab for treating atypical hemolytic uremic syndrome?

While there is no direct data on Crovalimab, similar drugs like Ravulizumab and Eculizumab, which also inhibit the complement system, have shown effectiveness in treating atypical hemolytic uremic syndrome by rapidly resolving symptoms and improving kidney function. ^{1 2 3 4 5}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for children with atypical Hemolytic Uremic Syndrome (aHUS) who weigh at least 5 kg and are vaccinated against certain infections. They must not have HIV, active hepatitis B/C, or other conditions that could cause similar symptoms. Those with a kidney transplant due to aHUS can join; females of childbearing age should use contraception.

Inclusion Criteria

For female participants of childbearing potential: an agreement to remain abstinent or use contraception

I have a specific genetic variation related to my condition.

My body weight is at least 5 kg.

Exclusion Criteria

I have not had a fever of 38°C or higher in the last 7 days.

My organs are failing.

I have been on chronic dialysis or have end-stage kidney disease.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive crovalimab, with cohorts for naive, switch, and pretreated participants

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Crovalimab (Monoclonal Antibodies)

Trial Overview The study tests Crovalimab's effectiveness and safety in treating pediatric aHUS patients. It includes those new to treatment, switching from another C5 inhibitor therapy, or having specific genetic variations affecting their response to such treatments.

Participant Groups

Group I: Crovalimab Experimental Treatment 1 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 C5 inhibitor and \[3\] Pretreated Cohort (includes C5 SNP (Single Nucleotide Polymorphism) participants) - participants who received treatment with another C5 inhibitor and subsequently discontinued it.

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

Chugai Pharmaceutical

Industry Sponsor

Trials

105

Recruited

25,000+

Dr. Osamu Okuda

Chugai Pharmaceutical

Chief Executive Officer since 2020

MD from Kyoto University

Dr. Mariko Y. Momoi

Chugai Pharmaceutical

Chief Medical Officer

MD from Jichi Medical University

Findings from Research

Eculizumab and ravulizumab are both effective and safe treatments for atypical hemolytic uremic syndrome (aHUS), but ravulizumab is preferred due to its lower financial burden and less frequent dosing, making it more convenient for patients and caregivers.

Genetic mutations in complement factors are linked to a higher risk of disease recurrence, suggesting that treatment should start promptly upon identifying these mutations to prevent complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eculizumab Versus Ravulizumab for the Treatment of Atypical Hemolytic Uremic Syndrome: A Systematic Review. Shahid, K., Qayyum, S.[2023]

In a clinical trial involving 10 pediatric patients with atypical hemolytic uremic syndrome (aHUS), switching from eculizumab to ravulizumab resulted in stable kidney function and hematologic parameters over a 52-week period, with no patients requiring dialysis.

Ravulizumab was found to be safe, with common adverse events being upper respiratory infections and oropharyngeal pain, but no serious infections or deaths reported, indicating a favorable safety profile for this long-acting C5 inhibitor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The long-acting C5 inhibitor, ravulizumab, is efficacious and safe in pediatric patients with atypical hemolytic uremic syndrome previously treated with eculizumab. Tanaka, K., Adams, B., Aris, AM., et al.[2022]

Hemolytic uremic syndrome (HUS) is linked to mutations in complement regulatory proteins, which can lead to atypical HUS (aHUS), highlighting the importance of genetic testing for better patient outcomes.

Current treatments include plasma infusion/exchange, but emerging complement inhibitor therapies show promise for improving treatment efficacy and patient prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complement regulatory genes and hemolytic uremic syndromes. Kavanagh, D., Richards, A., Atkinson, J.[2008]

Atypical uremic hemolytic syndrome is a serious condition caused by excessive activation of the complement system, leading to symptoms like hemolytic anemia, low platelet counts, and acute kidney failure, with genetic mutations found in up to 60% of patients.

Early diagnosis and treatment with eculizumab can significantly improve patient outcomes by quickly disrupting the disease process, reducing the need for dialysis and enhancing kidney function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of atypical uremic hemolytic syndrome in pregnant patient. Simón Polo, E., Hernández Laforet, J., Carretero de la Encarnación, B., et al.[2021]

Ravulizumab has shown long-term efficacy in treating atypical hemolytic uremic syndrome (aHUS), with a median follow-up of 76.7 weeks revealing sustained improvements in thrombotic microangiopathy (TMA) and kidney function in 58 patients.

The treatment demonstrated an acceptable safety profile, with most adverse events occurring early in the treatment and no cases of meningococcal infection or death during the follow-up period, indicating it is a safe option for long-term management of aHUS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Efficacy and Safety of the Long-Acting Complement C5 Inhibitor Ravulizumab for the Treatment of Atypical Hemolytic Uremic Syndrome in Adults. Barbour, T., Scully, M., Ariceta, G., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Eculizumab Versus Ravulizumab for the Treatment of Atypical Hemolytic Uremic Syndrome: A Systematic Review. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

The long-acting C5 inhibitor, ravulizumab, is efficacious and safe in pediatric patients with atypical hemolytic uremic syndrome previously treated with eculizumab. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Complement regulatory genes and hemolytic uremic syndromes. [2008]

4. Spain pubmed.ncbi.nlm.nih.gov

Management of atypical uremic hemolytic syndrome in pregnant patient. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Long-Term Efficacy and Safety of the Long-Acting Complement C5 Inhibitor Ravulizumab for the Treatment of Atypical Hemolytic Uremic Syndrome in Adults. [2022]