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

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

The protocol will be amended to describe Part B of the study after Part A data have been analyzed.

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