Crovalimab vs Eculizumab for Paroxysmal Nocturnal Hemoglobinuria

(COMMODORE 2 Trial)

Not currently recruiting at 156 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares the effectiveness of a new drug, crovalimab, to an existing drug, eculizumab, for treating paroxysmal nocturnal hemoglobinuria (PNH), a rare blood condition affecting red blood cells. Participants will receive either crovalimab or eculizumab to determine if the new treatment matches the effectiveness of the current one. Ideal candidates for this study are individuals diagnosed with PNH who have not yet tried treatments targeting the complement system, a part of the immune system. 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.

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.

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

Previous studies have generally shown that crovalimab is well-tolerated. Specifically, there were 8.9 serious infections per 100 patient-years, and no cases of meningococcal infections were reported. This is significant because meningococcal infections can be a concern with similar treatments.

Crovalimab also caused fewer side effects compared to similar treatments, resulting in fewer people experiencing issues directly from the drug.

Eculizumab, the other treatment in the trial, has already received FDA approval for other uses, indicating its safety for humans, although side effects can still occur.

Overall, research suggests that both treatments are generally safe, with crovalimab possibly causing fewer side effects. However, individual experiences may vary. ^{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 to treating Paroxysmal Nocturnal Hemoglobinuria (PNH). Unlike the standard treatment, eculizumab, which requires bi-weekly intravenous infusions, crovalimab can be administered as a subcutaneous injection. This not only makes it more convenient but also potentially enhances patient compliance and comfort. Additionally, crovalimab's dosing schedule after the initial phase allows for less frequent maintenance doses, which could improve the quality of life for patients managing this chronic condition.

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

In this trial, participants will receive either crovalimab or eculizumab to treat paroxysmal nocturnal hemoglobinuria (PNH). Previous studies have shown that crovalimab effectively maintains hemoglobin levels, reducing the need for blood transfusions and improving overall patient outcomes. Research indicates that 88-95% of patients maintained stable hemoglobin levels over time, and 86% experienced control over the breakdown of red blood cells. Another study showed that crovalimab performed as well as eculizumab, a long-standing treatment for PNH, in preventing the breakdown of red blood cells and reducing symptoms. These findings support the potential effectiveness of both crovalimab and eculizumab in treating 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 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

LDH level >= 2x ULN at screening (as per local assessment)

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 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

4 weeks

Open-label extension

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

Up to 5 years

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

Citations

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pubmed.ncbi.nlm.nih.gov

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

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ashpublications.org

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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- ...

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valueinhealthjournal.com

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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.

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sciencedirect.com

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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.

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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 ...