ALN-CFB for adults with PNH who remain anemic on C5 inhibitors

A Randomized, Double-Blind, Placebo-Controlled, First-In-Human Study of the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of ALN-CFB, an Investigational siRNA Therapeutic Against Complement Factor B, in Participants With Paroxysmal Nocturnal Hemoglobinuria and Persistent Anemia on Approved C5-Inhibitor Therapy

This trial will test ALN-CFB, an experimental siRNA medicine, versus placebo in adults with PNH who remain anemic despite taking a C5 inhibitor.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Regeneron Pharmaceuticals (Industry-sponsored)
• Drugs / interventions: eculizumab, ravulizumab, crovalimab
• Locations: 7 sites (Toronto, Ontario and 6 other locations)
• Trial ID: NCT07187401 on ClinicalTrials.gov

What this trial studies

This first-in-human phase 1/2 trial gives adults with PNH and persistent anemia either ALN-CFB or placebo while they remain on a stable C5 inhibitor. The study primarily measures safety and tolerability and also tracks drug levels, changes in Complement Factor B protein, and effects on red blood cell counts and hemolysis markers. Results from Part A will guide amendments and dosing for Part B. Participants will be closely monitored for adverse events, including infection risk related to complement modulation.

Who should consider this trial

Good fit: Adults with confirmed PNH who have been on a stable C5 inhibitor for at least 24 weeks, have hemoglobin ≤10.5 g/dL and a reticulocyte count ≥100×10^9/L, and meet other protocol criteria.

Not a fit: Patients with bone marrow failure, recent or ongoing serious infections, a history of meningococcal infection, or prior bone marrow/organ transplant are excluded and unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, ALN-CFB could lower CFB levels and reduce ongoing hemolysis, leading to higher hemoglobin and fewer transfusions for people who remain anemic on C5 inhibitors.

How similar studies have performed: Complement-targeting therapies have shown benefit in PNH (for example C3 inhibitors), but direct inhibition of Factor B via siRNA is a novel, early-stage approach with limited human data to date.

Eligibility criteria

Key Inclusion Criteria:

1. Has been diagnosed with PNH confirmed by a history of high flow cytometry from prior testing
2. Treated with a stable dose of C5 inhibitor (eculizumab or approved eculizumab biosimilar, ravulizumab, or crovalimab) for at least 24 weeks prior to screening visit, as described in the protocol
3. Has hemoglobin ≤10.5 g/dL at screening visit 1, with evidence of anemia prior to this visit, as described in the protocol
4. Has peripheral blood reticulocyte count of ≥100 x 10\^9/L at screening visit 1

Key Exclusion Criteria:

1. Has history of bone marrow transplantation or receipt of an organ transplant
2. Has history of meningococcal infection or similar recurrent infections by other encapsulated bacterial organisms
3. Has any active, ongoing infection or a recent infection requiring ongoing systemic treatment with antibiotics, antivirals, or antifungals within 2 weeks of screening or during the screening period
4. Has laboratory evidence of bone marrow failure, as described in the protocol
5. Have recent, unstable medical conditions, not related to PNH or PNH-related complications, as described in the protocol

NOTE: Other Protocol Defined Inclusion / Exclusion Criteria Apply

Where this trial is running

Toronto, Ontario and 6 other locations

• Toronto General Hospital — Toronto, Ontario, Canada (Recruiting)
• St. Vincent Hospital - The Catholic University of Korea — Suwon, Gyeonggi-do, South Korea (Recruiting)
• Seoul National University Hospital — Seoul, South Korea (Recruiting)
• The Catholic University of Korea, Seoul St. Mary's Hospital — Seoul, South Korea (Recruiting)
• Severance Hospital — Seoul, South Korea (Recruiting)
• Samsung Medical Center — Seoul, South Korea (Recruiting)
• St. James's University Hospital — Leeds, West Yorkshire, United Kingdom (Recruiting)

Study contacts

• Study coordinator: Clinical Trials Administrator

Conditions Paroxysmal Nocturnal Hemoglobinuria; Persistent Anemia; C5 inhibitor; Complement Factor B protein; Red Blood Cells