Crovalimab for Atypical Hemolytic Uremic Syndrome

(COMMUTE-a Trial)

Recruiting at 108 trial locations

Overseen By Reference Study ID Number: BO42353 https://forpatients.roche.com/

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must be taking: C5 inhibitors

Must not be taking: Tranexamic acid, IVIg

Disqualifiers: Non-aHUS renal disease, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

83 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial allows participants to continue taking certain medications like immunosuppressants, corticosteroids, mTOR inhibitors, or calcineurin inhibitors, as long as the dose has been stable for at least 28 days before starting the trial. The protocol does not specify about other medications, so it's best to discuss with the trial team.

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

Research on similar drugs like ravulizumab and eculizumab, which also target the complement system, shows they are effective in treating atypical hemolytic uremic syndrome by rapidly resolving symptoms and improving kidney function. This suggests that Crovalimab, which works in a similar way, may also be effective. ^{1 2 3 4 5}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

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.

Inclusion Criteria

I have been treated with eculizumab or ravulizumab.

I have shown improvement with a C5 inhibitor treatment.

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

Exclusion Criteria

I have recently taken tranexamic acid.

I will start or have started PE/PI treatment within 8 weeks before my first crovalimab dose.

You have cryoglobulinemia when you are screened for the study, especially if you have recently been treated with a C5 inhibitor.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive crovalimab for 24 weeks to evaluate efficacy and safety

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Crovalimab

Trial Overview 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.

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 Complement Component 5 (C5) inhibitor and \[3\] C5 Single Nucleotide Polymorphism (C5 inhibitor) Cohort - participants with documented C5 polymorphism.

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

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]

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]

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]

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]

References

1. 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]

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

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

3. 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]

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

Complement regulatory genes and hemolytic uremic syndromes. [2008]