A First-in-Human Safety and Efficacy Study of ALN-CFB, a Small Interfering RNA (siRNA) Targeting Complement Factor B, in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria With Persistent Anemia on a C5 Inhibitor
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
Regeneron Pharmaceuticals
24 participants
Feb 11, 2026
INTERVENTIONAL
Summary
This study is researching an experimental drug called ALN-CFB. The study is focused on people with Paroxysmal Nocturnal Hemoglobinuria (PNH) who are currently taking a complement component C5 inhibitor ("C5-inhibitor") and continue to have anemia (low red blood cell count). The aim of the study is to see how tolerable ALN-CFB is compared to placebo. A placebo looks like the study drug but does not contain any drug. The study is looking at several other research questions, including: * What side effects may happen from taking ALN-CFB * How much ALN-CFB is in the blood at different times * How much Complement Factor B (CFB) protein levels in the blood are affected by ALN-CFB
Eligibility
Inclusion Criteria4
- Has been diagnosed with PNH confirmed by a history of high flow cytometry from prior testing
- 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
- Has hemoglobin ≤10.5 g/dL at screening visit 1, with evidence of anemia prior to this visit, as described in the protocol
- Has peripheral blood reticulocyte count of ≥100 x 10\^9/L at screening visit 1
Exclusion Criteria5
- Has history of bone marrow transplantation or receipt of an organ transplant
- Has history of meningococcal infection or similar recurrent infections by other encapsulated bacterial organisms
- 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
- Has laboratory evidence of bone marrow failure, as described in the protocol
- Have recent, unstable medical conditions, not related to PNH or PNH-related complications, as described in the protocol
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Interventions
Administered as defined in the protocol
Administered as defined in the protocol
Locations(7)
View Full Details on ClinicalTrials.gov
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NCT07187401