Crovalimab for Atypical Hemolytic Uremic Syndrome

(COMMUTE-a Trial)

Not currently recruiting at 123 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests crovalimab, a new treatment for people with atypical Hemolytic Uremic Syndrome, a rare condition causing blood clots and kidney problems. The trial aims to evaluate the effectiveness and safety of crovalimab. Participants will join one of three groups: those who haven't tried similar treatments, those switching from another treatment, and those with a specific genetic trait affecting treatment. Individuals who have had a kidney transplant or have poorly controlled symptoms with current treatments might be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to the development of a potentially groundbreaking treatment.

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.

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

Research has shown that crovalimab has been tested in various studies to assess its safety for people with atypical Hemolytic Uremic Syndrome (aHUS). In these studies, most participants tolerated crovalimab well. Some side effects were reported, but they were usually mild to moderate.

This trial is a Phase 3 study, indicating that crovalimab has already undergone earlier testing stages in humans, focusing on its safety. Phase 3 trials involve more participants to confirm its effectiveness and monitor side effects. This suggests some confidence in the safety of crovalimab based on previous trials.

For those considering joining a trial, it is important to know that crovalimab has passed initial safety checks and is now being tested in a larger group to confirm these results. Always consult a healthcare provider to understand what participation might mean personally. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for aHUS?

Crovalimab is unique because it targets and inhibits Complement Component 5 (C5), which is a key part of the immune system's response that can lead to damage in atypical hemolytic uremic syndrome (aHUS). Unlike existing treatments like eculizumab and ravulizumab, which also inhibit C5, crovalimab is designed to be administered less frequently, potentially improving convenience and adherence for patients. Additionally, crovalimab's ability to target patients with specific C5 genetic polymorphisms means it could offer a more tailored approach to treatment, which is an exciting development for personalized medicine. This combination of less frequent dosing and personalized treatment strategies is what makes researchers optimistic about crovalimab's potential.

What evidence suggests that crovalimab might be an effective treatment for aHUS?

Research has shown that crovalimab might help treat atypical hemolytic uremic syndrome (aHUS). Studies have found that crovalimab blocks a part of the immune system called C5, which plays a role in aHUS. Early results suggest that crovalimab can reduce damage to blood vessels by preventing excessive immune activity. This trial tests crovalimab in different groups, including participants new to this therapy, those switching from other treatments, and those with a documented C5 polymorphism. Patients who previously used crovalimab showed improvement, indicating its potential effectiveness. ^{1 4 6 7 8}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04861259

NCT04861259 | A Study Evaluating the Efficacy, Safety, ... Study Overview. This study aims to evaluate the efficacy and safety of crovalimab in adult and adolescent participants with aHUS.

2. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/blood-disorder/atypical-hemolytic-uremic-syndrome/a-study-evaluating-the-efficacy--safety--pharmacokineti-90194.html

Clinical Study aHUS Crovalimab | ForPatients-Roche A clinical trial to look at how safe and effective crovalimab is in children and adolescents with atypical haemolytic uraemic syndrome (aHUS)

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04958265

NCT04958265 | A Study Evaluating the Efficacy, Safety, ... This study aims to evaluate the efficacy and safety of crovalimab in pediatric participants with aHUS. Official Title. A Phase III, Multicenter, Single-Arm ...

4. clinicaltrial.be clinicaltrial.be/en/details/44654?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

A Study Evaluating the Efficacy, Safety, Pharmacokinetics... This study aims to evaluate the efficacy and safety of crovalimab in adult and adolescent participants with aHUS.

5. bmjopen.bmj.com bmjopen.bmj.com/content/15/5/e100159

Efficacy and safety of novel complement inhibitors in ... This protocol elaborates the systematic review plans to evaluate the effectiveness and the drug safety of complement inhibitors in aHUS.

6. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/blood-disorder/atypical-hemolytic-uremic-syndrome/a-study-evaluating-the-efficacy--safety--pharmacokineti-29406.html

Clinical Trial – Atypical Hemolytic Uremic Syndrome – Eff... Access the clinical trial testing the efficacy, safety, pharmacokinetics, and pharmacodynamics of crovalimab in adult and adolescent patients with atypical ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04958265

NCT04958265 | A Study Evaluating the Efficacy, Safety, ... This study aims to evaluate the efficacy and safety of crovalimab in pediatric participants with aHUS. Official Title. A Phase III, Multicenter, Single-Arm ...

8. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-effects-and-safety-of-crovalimab-for-adults-and-adolescents-with-atypical-hemolytic-uremic-syndrome-ahus/

Study on the Effects and Safety of Crovalimab for Adults ... This clinical trial is investigating the safety and efficacy of Crovalimab, an injectable treatment, in managing Atypical Hemolytic Uremic ...