Crovalimab vs Eculizumab for Paroxysmal Nocturnal Hemoglobinuria

(COMMODORE 1 Trial)

Not currently recruiting at 165 trial locations

Overseen By Reference Study ID Number: BO42161 https://forpatients.roche.com/

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must be taking: Complement inhibitors

Disqualifiers: Bone marrow transplant, Myelodysplastic syndrome, Hepatitis B/C, 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: 2

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of two medications, crovalimab and eculizumab, for individuals with paroxysmal nocturnal hemoglobinuria (PNH), a rare blood condition. Participants will receive either crovalimab or eculizumab to evaluate their effects. The trial seeks individuals who have used eculizumab or ravulizumab for PNH for at least three months and have a confirmed PNH diagnosis. The goal is to determine if crovalimab is a safe and effective alternative to eculizumab. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must have been treated with eculizumab or ravulizumab for at least 3 months before starting the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that crovalimab is generally well-tolerated. Studies indicate it has fewer side effects compared to some other treatments, with fewer reports of infections and other negative effects. Serious infections with crovalimab occur at a rate of 8.9 events per 100 person-years. Notably, there were no reports of meningococcal infections, a serious issue with some treatments.

Eculizumab, already approved by the FDA for other conditions, has a well-known safety profile. However, like any medication, it can cause side effects, such as headaches, tiredness, or more serious issues like infections.

Both treatments have undergone extensive study, and many patients have used them safely. However, individual reactions can vary, so monitoring for any side effects is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about crovalimab because it offers a new approach for treating Paroxysmal Nocturnal Hemoglobinuria (PNH). Unlike eculizumab, which is the current standard of care, crovalimab can be administered subcutaneously, which may be more convenient for patients compared to eculizumab's intravenous administration. Additionally, crovalimab works by targeting a specific part of the complement system involved in PNH, potentially offering a more precise treatment option. These features could lead to improved patient compliance and outcomes, making crovalimab a promising alternative for those with PNH.

What evidence suggests that this trial's treatments could be effective for paroxysmal nocturnal hemoglobinuria?

This trial will compare Crovalimab and Eculizumab for treating paroxysmal nocturnal hemoglobinuria (PNH), a rare blood disorder. Studies have shown that Crovalimab, which participants in this trial may receive, effectively stabilizes hemoglobin levels and reduces the need for blood transfusions. In trials, 88-95% of patients met their treatment goals, with most preferring Crovalimab over other treatments like Eculizumab. Additionally, direct comparisons have shown Crovalimab to be similarly effective to Eculizumab. Overall, these findings support Crovalimab as a promising treatment option for PNH. ^{5 6 7 8 9}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

This trial is for adults with PNH who weigh at least 40 kg and have been treated with eculizumab or ravulizumab for over 3 months. They should have stable lactate dehydrogenase levels and be vaccinated against Neisseria meningitidis. Pregnant women, those planning pregnancy, or breastfeeding are excluded, as well as individuals with certain medical conditions or treatments that could interfere.

Inclusion Criteria

My body weight is at least 40 kg.

I agree to avoid pregnancy or use birth control during and after treatment.

I am willing and able to follow all study requirements.

Exclusion Criteria

I have a history of or currently have cryoglobulinemia.

My condition is classified as intermediate to very high risk according to the IPSS-R for myelodysplastic syndrome.

I have had a bone marrow transplant from another person.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either crovalimab or eculizumab for 24 weeks

24 weeks

Weekly visits initially, then every 2-4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 weeks

Open-label extension

Participants who benefit from crovalimab may continue treatment

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Crovalimab
• Eculizumab

Trial Overview The study compares the safety and effectiveness of Crovalimab to Eculizumab in patients already receiving complement inhibitors for PNH. About 190 participants will receive either Crovalimab or Eculizumab to determine if there's a difference in how they affect the disease.

How Is the Trial Designed?

Group I: Arm C (Crovalimab) (Exploratory) Experimental Treatment 1 Intervention

Participants with a body weight ≥ 5 to \<12 kilograms (kg) will receive a loading series of crovalimab doses comprised of an IV dose on Day 1 of Week 1, followed by crovalimab SC dose on Day 2 Week 1. Maintenance doses will begin at Week 3 and will be administered Q2W, thereafter. Participants with a body weight ≥ 12 to \< 20 kg and ≥ 20 kg will receive a loading series of crovalimab doses comprised of an IV dose on Day 1 of Week 1, followed by weekly crovalimab SC doses for 4 weeks at Week 1 (Day 2) and then at Weeks 2, 3, and 4. Maintenance doses will begin at Week 5 and will be administered Q2W thereafter, for participants with a body weight ≥ 12 to \< 20 kg and Q4W thereafter, for participants with a body weight \> 20 kg. After 24 weeks of crovalimab treatment, participants who derive benefit from the drug may continue to receive crovalimab.

Group II: Arm A (Crovalimab) Experimental Treatment 1 Intervention

Participants will receive a loading series of crovalimab comprised of an intravenous (IV) 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 24 weeks of study treatment. After 24 weeks of crovalimab treatment, participants who derive benefit from the drug may continue to receive crovalimab.

Group III: Arm B (Eculizumab) Active Control 1 Intervention

Participants will receive an approved maintenance dose of eculizumab starting on Day 1 and every 2 weeks (Q2W) thereafter for a total of 24 weeks of study treatment. After 24 weeks of study eculizumab treatment, participants will have the option to switch to crovalimab or to discontinue from the study after completion of 10 weeks of safety follow-up.

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

Eculizumab treatment led to a significant 50% reduction in transfusions for patients with a history of transfusion, decreasing from an average of 10.6 units per patient-year to 5.4 units after treatment.

The therapy also resulted in a 70% decrease in thrombotic events and major adverse vascular events, indicating its broad efficacy regardless of patients' transfusion or bone marrow disease history.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beneficial effects of eculizumab regardless of prior transfusions or bone marrow disease: Results of the International Paroxysmal Nocturnal Hemoglobinuria Registry. Röth, A., Araten, DJ., Larratt, L., et al.[2021]

Patients with paroxysmal nocturnal hemoglobinuria (PNH) treated with either ravulizumab or eculizumab for 26 weeks reported better quality of life and functioning compared to the general population, indicating the efficacy of these treatments.

Ravulizumab showed larger effect sizes than eculizumab, and both treatments facilitated adaptive changes in patients' responses over time, suggesting they not only manage symptoms but also improve overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Norm-based comparison of the quality-of-life impact of ravulizumab and eculizumab in paroxysmal nocturnal hemoglobinuria. Schwartz, CE., Stark, RB., Borowiec, K., et al.[2021]

In a phase 3 study involving 195 patients with paroxysmal nocturnal hemoglobinuria (PNH), ravulizumab, administered every 8 weeks, was found to be noninferior to eculizumab, which is given every 2 weeks, in terms of key efficacy measures such as lactate dehydrogenase (LDH) levels and breakthrough hemolysis.

The switch from eculizumab to ravulizumab was safe, with no reported meningococcal infections or discontinuations due to adverse events, although headaches were more common in the ravulizumab group (26.8% vs. 17.3% for eculizumab).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor-experienced adult patients with PNH: the 302 study. Kulasekararaj, AG., Hill, A., Rottinghaus, ST., et al.[2021]

In a study involving 23 Japanese adults with paroxysmal nocturnal hemoglobinuria (PNH), 82.6% preferred ravulizumab over eculizumab, highlighting a strong patient preference for the new treatment.

The preference for ravulizumab was primarily due to its longer infusion interval of every 8 weeks compared to eculizumab's 2-week schedule, which enhances treatment convenience and overall quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Japanese patient preferences between ravulizumab and eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria]. Ishiyama, K., Usuki, K., Ikezoe, T., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11918723/

Crovalimab: a new era in paroxysmal nocturnal ... Crovalimab has been proven effective in maintaining hemoglobin levels, reducing the need for transfusions, and improving patient outcomes by ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40515823/

Patient-reported outcomes in patients with paroxysmal ... Across studies, most patients (60–85%; including COMMODORE 1 non-randomized patients) preferred crovalimab to eculizumab or ravulizumab (Patient ...

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/4078/529775/Phase-III-COMMODORE-1-Trial-2-Year-Efficacy-and

Phase III COMMODORE 1 Trial: 2-Year Efficacy and Safety of ... From W25-97, across 24-wk intervals, 88-95% of pts achieved TA and 88-93% achieved hb stabilization. BTH occurred in 26% (7/27) of pts from BL- ...

4. valueinhealthjournal.com valueinhealthjournal.com/article/S1098-3015(25)00263-3/fulltext

CO54 Systematic Literature Review and Network Meta ... In the randomized, Phase III COMMODORE 2 (C5 inhibitor-naive) study, crovalimab showed non-inferior efficacy outcomes vs eculizumab.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265025028162

CT-910: Efficacy and Safety of Crovalimab for Paroxysmal ... We found a significant pooled hemolysis control rate of 86% (95% CI: 77–49%, I2 = 73%) in patients with PNH treated with crovalimab. There was a 77% transfusion ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39535306/

Safety of Crovalimab Versus Eculizumab in Patients With ... Serious infection rates were 8.9 and 13.7 AEs per 100 PY, respectively; no meningococcal infections were reported. Fatal AEs occurred in eight ( ...

7. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/5218/526544/Safety-and-Efficacy-of-Corvalimab-in-Paroxysmal

Safety and Efficacy of Corvalimab in Paroxysmal Nocturnal ... We found that crovalimab showed less prevalence of both any-cause and treatment- related adverse events, a high proportion of patients with controlled ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124068368

Phase III COMMODORE 1 Trial: 2-Year Efficacy and Safety ... Most pts who switched from ravu to crova maintained hemolysis control through W25, consistent with COMMODORE 1 randomized data.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT04434092

NCT04434092 | A Study Evaluating the Efficacy and Safety ... Safety of Crovalimab Versus Eculizumab in Patients With Paroxysmal Nocturnal Haemoglobinuria (PNH): Pooled Results From the Phase 3 COMMODORE Studies. Eur J ...