What side effects are associated with this type of intervention?

The most common treatments for Paroxysmal Nocturnal Hemoglobinuria (PNH) involving complement inhibition, such as Crovalimab and Eculizumab, are generally well-tolerated but can have side effects. Common side effects include headaches, upper respiratory tract infections, and infusion-related reactions. More serious but less frequent side effects can include an increased risk of meningococcal infections due to the suppression of the complement system, which is crucial for fighting certain bacterial infections. Patients are often advised to receive meningococcal vaccination prior to starting treatment to mitigate this risk.

What prior FDA approvals exist?

The FDA has approved several treatments for Paroxysmal Nocturnal Hemoglobinuria (PNH) that focus on complement inhibition. Eculizumab, a monoclonal antibody that inhibits the complement protein C5, was the first to be approved and has been a cornerstone in PNH treatment. Another similar drug, Ravulizumab, also targets C5 and offers a longer dosing interval compared to Eculizumab. These therapies work by preventing the destruction of red blood cells, thereby reducing hemolysis and improving patient outcomes.

What other types of research exist?

As of now, there are no specific novel alternatives to Crovalimab and Eculizumab mentioned in the provided context for the treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH). Patients should consult with their healthcare provider to discuss the latest treatment options and ongoing clinical trials that may offer new therapeutic possibilities.

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Monoclonal Antibodies

Crovalimab vs Eculizumab for Paroxysmal Nocturnal Hemoglobinuria (COMMODORE 1 Trial)

Phase 3

Recruiting

Research Sponsored by Hoffmann-La Roche

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Body weight >= 40 kg at screening

Documented diagnosis of PNH, confirmed by high sensitivity flow cytometry

Must not have

History of or ongoing cryoglobulinemia at screening

History of myelodysplastic syndrome with Revised International Prognostic Scoring System (IPSS-R) prognostic risk categories of intermediate, high and very high

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 8 years

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects may include reactions related to the immune system such as infections due to lowered immunity, allergic reactions during infusion of the drugs, and possibly other unknown risks associated with new medications.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My body weight is at least 40 kg.

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My PNH diagnosis was confirmed with a specific blood test.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a history of or currently have cryoglobulinemia.

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

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I have had a bone marrow transplant from another person.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 8 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 8 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 8 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Percentage of Participants with Adverse Events (AEs) and by Severity

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Group I: Arm C (Crovalimab) (Exploratory)Experimental Treatment1 Intervention

Participants will receive a loading series of Crovalimab comprised of an IV dose on Week 1 Day 1, followed by weekly crovalimab 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 be administered Q4W thereafter. After 24 weeks of crovalimab treatment, participants who derive benefit from the drug may continue to receive crovalimab.

Group II: Arm A (Crovalimab)Experimental Treatment1 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 Q4W (every 4 weeks) 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 Control1 Intervention

Participants will receive an approved maintenance dose of eculizumab starting on Day 1 and Q2W (every 2 weeks) 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.

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Paroxysmal Nocturnal Hemoglobinuria (PNH) are complement inhibitors such as Crovalimab and Eculizumab. These treatments work by inhibiting the complement system, specifically targeting the C5 protein to prevent its cleavage into C5a and C5b. This inhibition is crucial because it stops the formation of the membrane attack complex (MAC), which is responsible for the destruction of red blood cells in PNH patients. By preventing this hemolysis, complement inhibitors reduce symptoms such as anemia, fatigue, and the risk of thrombosis, thereby significantly improving the quality of life and prognosis for PNH patients.