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

June 17, 2026 updated by: Regeneron Pharmaceuticals

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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

Study Type

Interventional

Enrollment (Estimated)

24

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2C4
  • South Korea
      • Seoul, South Korea, 03080
        • Recruiting
        • Seoul National University Hospital
      • Seoul, South Korea, 6351
        • Recruiting
        • Samsung Medical Center
        • Contact:
      • Seoul, South Korea, 06591
        • Recruiting
        • The Catholic University of Korea, Seoul St. Mary's Hospital
        • Contact:
      • Seoul, South Korea, 3722
        • Recruiting
        • Severance Hospital
        • Contact:
    • Gyeonggi-do
      • Suwon, Gyeonggi-do, South Korea, 16247
        • Recruiting
        • St. Vincent Hospital - The Catholic University of Korea
        • Contact:
  • United Kingdom
      • London, United Kingdom, SE5 9RS
        • Recruiting
        • Kings College Hospital NHS Foundation Trust
    • West Yorkshire
      • Leeds, West Yorkshire, United Kingdom, LS97TF
        • Recruiting
        • St. James's University Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Drug: Placebo
Administered as defined in the protocol
Experimental: Single-Ascending Dose Escalation
Drug: ALN-CFB
Administered as defined in the protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Occurrence of Treatment-Emergent Adverse Events (TEAEs)
Time Frame: Through 365 Days
Through 365 Days
Severity of TEAEs
Time Frame: Through 365 Days
Through 365 Days

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Regeneron Pharmaceuticals

Investigators

  • Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 11, 2026

Primary Completion (Estimated)

November 29, 2029

Study Completion (Estimated)

July 15, 2031

Study Registration Dates

First Submitted

September 18, 2025

First Submitted That Met QC Criteria

September 18, 2025

First Posted (Actual)

September 23, 2025

Study Record Updates

Last Update Posted (Actual)

June 18, 2026

Last Update Submitted That Met QC Criteria

June 17, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ALN-CFB-PNH-2468
  • 2024-519806-11-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.

IPD Sharing Time Frame

When Regeneron has:

  • received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
  • made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
  • the legal authority to share the data, and
  • ensured the ability to protect participant privacy

IPD Sharing Access Criteria

Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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