Crovalimab vs Eculizumab for Paroxysmal Nocturnal Hemoglobinuria

(COMMODORE 2 Trial)

Recruiting at 143 trial locations

Overseen By Reference Study ID Number: BO42162 https://forpatients.roche.com/

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must not be taking: Complement inhibitors

Disqualifiers: Bone marrow transplant, Myelodysplastic syndrome, Pregnancy, 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

204 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. However, if you are currently or have previously been treated with a complement inhibitor, you cannot participate in the trial.

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

Eculizumab has been shown to significantly improve survival and quality of life for patients with paroxysmal nocturnal hemoglobinuria by blocking the breakdown of red blood cells and reducing the risk of blood clots. However, the response to eculizumab varies, with only about one-third of patients achieving normal hemoglobin levels. ^{1 2 3 4 5}

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 the most common side effect being headaches. No serious infections or treatment discontinuations due to side effects were reported in the studies. ^{3 4 6 7 8}

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. ^{1 2 3 4 9}

What is the purpose of this trial?

This trial is testing if crovalimab is as effective as eculizumab in treating people with PNH who haven't received similar treatments before. Both medications help prevent the immune system from attacking red blood cells. Eculizumab is a treatment for paroxysmal nocturnal hemoglobinuria (PNH) that decreases intravascular hemolysis and thrombosis and improves survival.

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for individuals with Paroxysmal Nocturnal Hemoglobinuria (PNH) who haven't been treated with complement inhibitors before. They must be willing to follow the study's procedures, weigh at least 40 kg, have certain vaccination against meningitis, and not be pregnant or breastfeeding. People previously treated with similar drugs or having certain health conditions are excluded.

Inclusion Criteria

My weight is at least 40 kg.

Willingness and ability to comply with all study visits and procedures

My PNH diagnosis was confirmed with a specific blood test.

Exclusion Criteria

Concurrent disease, treatment, procedure or surgery, or abnormality in clinical laboratory tests that could interfere with the conduct of the study, may pose any additional risk for the participant, or would, in the opinion of the Investigator, preclude the participant's safe participation in and completion of the study

I have a history of or currently have cryoglobulinemia.

I have been treated with a complement inhibitor.

Timeline

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

4 weeks

Open-label extension

Participants may continue to receive crovalimab for up to 5 years if they derive benefit

Up to 5 years

Treatment Details

Interventions

• Crovalimab
• Eculizumab

Trial Overview The trial is testing Crovalimab against Eculizumab in about 200 participants to see if it's just as effective for PNH patients who haven't used complement inhibitors. It will compare how well each drug works and monitor safety over time.

Participant Groups

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

Participants with a body weight ≥ 5 to \<12 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

Crovalimab will be administered at an initial loading dose of 1000 milligrams (mg) (for participants with body weight between 40 and 100 kilograms \[kg\]) or 1500 mg (for participants with body weight ≥ 100 kg), as intravenous (IV) injection on Day 1 of Week 1 followed by four weekly subcutaneous (SC) injections of 340 mg starting on Day 2 of Week 1 and then once weekly (QW) at Weeks 2,3 and 4. Thereafter crovalimab will be administered, as SC injection, at a maintenance dose of 680 mg (for participants with body weight between 40 and 100 kg) or 1020 mg (for participants with body weight ≥ 100 kg) once every 4 weeks (Q4W) from Week 5 for a total of 24 weeks of study treatment. Participants may continue to receive crovalimab after 24 weeks of treatment up to maximum of 5 years.

Group III: Arm B (Eculizumab) Active Control 2 Interventions

Participants will receive loading dose of eculizumab 600 mg on Days 1, 8, 15, and 22, followed by maintenance dose of 900 mg on Day 29 and every 2 weeks (Q2W) thereafter until 24 weeks. Participants may switch to receive crovalimab after 24 weeks of eculizumab treatment.

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

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]

References

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]