Crovalimab vs Eculizumab for Paroxysmal Nocturnal Hemoglobinuria

(COMMODORE 1 Trial)

Recruiting at 135 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

190 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing the safety of crovalimab and eculizumab in patients with PNH who are already on medications. Both drugs work by stopping the immune system from destroying red blood cells. Eculizumab, a medication that was first approved for PNH in 2007, has revolutionized the treatment of this disease.

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 Crovalimab or Eculizumab safe for humans?

Eculizumab has been shown to have a similar safety profile to other treatments for paroxysmal nocturnal hemoglobinuria, with headache being the most common side effect. No serious infections or treatment discontinuations due to side effects were reported in the studies. ^{1 2 3 4 5}

How does the drug Crovalimab differ from Eculizumab for treating paroxysmal nocturnal hemoglobinuria?

Crovalimab is a newer treatment option for paroxysmal nocturnal hemoglobinuria (PNH) that may offer different dosing schedules or mechanisms compared to Eculizumab, which is known for its ability to block the breakdown of red blood cells and improve quality of life. While Eculizumab requires frequent infusions, newer treatments like Ravulizumab, which is similar to Crovalimab, offer less frequent dosing, potentially improving convenience and quality of life for patients. ^{2 3 6 7 8}

What data supports the effectiveness of the drug Crovalimab for treating paroxysmal nocturnal hemoglobinuria?

Eculizumab, a similar drug to Crovalimab, has been shown to significantly improve survival and quality of life for patients with paroxysmal nocturnal hemoglobinuria by reducing blood cell destruction and the risk of blood clots. This suggests that Crovalimab, which is being compared to Eculizumab, may also be effective in treating this condition. ^{2 3 6 7 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 am willing and able to follow all study requirements.

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

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

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]

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]

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]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Emerging drugs for the treatment of paroxysmal nocturnal hemoglobinuria. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Assessing Preferences for Rare Disease Treatment: Qualitative Development of the Paroxysmal Nocturnal Hemoglobinuria Patient Preference Questionnaire (PNH-PPQ&#169;). [2022]

3. Japan pubmed.ncbi.nlm.nih.gov

[Japanese patient preferences between ravulizumab and eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria]. [2023]

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

Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor-experienced adult patients with PNH: the 302 study. [2021]

5. England 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. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Effect of eculizumab treatment in patients with paroxysmal nocturnal hemoglobinuria with or without high disease activity: Real-world findings from the International Paroxysmal Nocturnal Hemoglobinuria Registry. [2022]

7. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[The efficacy and safety of eculizumab biosimilar in patients with paroxysmal nocturnal hemoglobinuria. Results of a phase III randomized open-label comparative clinical trial]. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Norm-based comparison of the quality-of-life impact of ravulizumab and eculizumab in paroxysmal nocturnal hemoglobinuria. [2021]

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

Efficacy and Safety of Eculizumab for Paroxysmal Nocturnal Hemoglobinuria: A Systematic Review and Meta-Analysis. [2023]