Pozelimab + cemdisiran for adults with PNH whose current treatment isn't working

A Single Arm Study to Evaluate the Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy in Patients With Paroxysmal Nocturnal Hemoglobinuria With Inadequate Control of Intravascular Hemolysis on Currently Available C5 Inhibitor Therapy

This trial tests whether combining pozelimab and cemdisiran can better reduce hemolysis in adults with PNH whose C5 inhibitor treatment isn’t controlling their disease.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 35 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Regeneron Pharmaceuticals (industry)
• Drugs / interventions: eculizumab, ravulizumab, crovalimab, pozelimab
• Locations: 8 sites (Florence, Tuscany and 7 other locations)
• Trial ID: NCT07154745 on ClinicalTrials.gov

What this trial studies

This is a Phase 3, interventional trial testing a combination of two investigational agents, pozelimab and cemdisiran, in adults with PNH who have persistent hemolysis despite treatment with approved C5 inhibitors. Eligible participants must have been on labeled doses of eculizumab, ravulizumab, or crovalimab for at least six months and have persistently elevated LDH (>1.5× ULN) attributed to intravascular hemolysis. The treatment program includes a 28-week primary treatment period followed by a 52-week extension, with monitoring for hemolysis markers, safety, drug levels, and anti-drug antibodies. The study will collect adverse event data and pharmacokinetic/pharmacodynamic measures to determine whether the combination improves disease control and is tolerable.

Who should consider this trial

Good fit: Adults with confirmed PNH who have been on eculizumab, ravulizumab, or crovalimab at labeled doses for at least six months and have persistently elevated LDH (>1.5× ULN) due to intravascular hemolysis are the intended participants.

Not a fit: Patients with known or suspected C5 mutations that render C5-targeting drugs ineffective, recent hematologic transplants, body weight under 40 kg, or those whose disease is already well controlled on current therapy are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, the combination could lower hemolysis and reduce transfusion needs or disease symptoms for patients not adequately controlled by existing C5 inhibitors.

How similar studies have performed: Approved C5 inhibitors like eculizumab and ravulizumab have shown clear benefit in PNH, but the pozelimab plus cemdisiran combination is a newer approach with limited phase 3 data to date.

Eligibility criteria

Key Inclusion Criteria:

1. Diagnosis of PNH confirmed by a history of high-sensitivity flow cytometry from prior testing
2. Currently treated with marketed eculizumab, ravulizumab, or crovalimab at the labeled dose for at least 6 months
3. LDH persistently \> 1.5 × Upper Limit of Normal (ULN) in the previous 6 months that the Principal Investigator (PI) attributes is due to intravascular hemolysis
4. At least 2 screening LDH values from different visits as described in the protocol
5. Willing and able to comply with clinic/remote visits and study-related procedures, including completion of the full series of meningococcal vaccinations required per protocol and agreement to continue to remain up to date with these vaccinations during the study

Key Exclusion Criteria:

1. Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplants
2. Body weight \<40 kilograms at screening visit
3. Patients with a known or suspected C5 mutation that is refractory to their current C5i treatment as described in the protocol
4. Any active or ongoing infection within 2 weeks of screening or during the screening period or any recent infection as described in the protocol
5. Known hereditary complement deficiency

Note: Other protocol-defined Inclusion/ Exclusion Criteria apply

Where this trial is running

Florence, Tuscany and 7 other locations

• AOU Careggi — Florence, Tuscany, Italy (RECRUITING)
• SC Hematology, AOU Città della Salute e della Scienza di Torino — Torino, Italy (RECRUITING)
• In-Vivo Sp. z o.o. — Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland (RECRUITING)
• Seoul National University Hospital — Seoul, South Korea (RECRUITING)
• Seoul St. Mary's Hospital - The Catholic University of Korea — Seoul, South Korea (RECRUITING)
• Ewha Womans University Mokdong Hospital — Seoul, South Korea (RECRUITING)
• Hospital Universitario Basurto — Bilbao, Vizcaya, Spain (RECRUITING)
• Hospital San Pedro de Alcantara — Cáceres, Spain (RECRUITING)

Study contacts

• Study coordinator: Clinical Trials Administrator

Conditions: Paroxysmal Nocturnal Hemoglobinuria, PNH