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

Not Applicable

Not yet recruiting

• Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH); Persistent Anemia
• Interventions: Drug: ALN-CFB; Drug: Placebo

• Registration Number: NCT07187401
• Lead Sponsor: Regeneron Pharmaceuticals

Brief 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

Detailed Description

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

Study Timeline

• Status Verified: 2025-09
• Study First Submitted: 2025-09-18
• Study First Submitted QC: 2025-09-18
• Last Update Submitted: 2025-09-18
• Study First Posted: 2025-09-23
• Last Update Posted: 2025-09-23
• Study Start: 2025-10-13
• Primary Completion: 2029-09-14
• Study Completion: 2029-12-07

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 24

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Single-Ascending Dose Escalation	ALN-CFB	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Occurrence of Treatment-Emergent Adverse Events (TEAEs)	Through 365 Days
Severity of TEAEs	Through 365 Days

Secondary Outcome Measures

Name	Time	Method
Concentrations of combined ALN-CFB and major metabolites in plasma	Through 365 Days
Concentrations of combined ALN-CFB and major metabolites in urine	Through 24 Hours following ALN-CFB administration
Absolute change from baseline in CFB concentration	Baseline, Through 365 Days
Percentage change from baseline in CFB concentration	Baseline, Through 365 Days