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

NCT07187401 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: ALN-CFB-PNH-24682024-519806-11-00
• Study Type: interventional
• Target: 24
• Locations: 3 countries
• Sites: 7

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

Conditions

Paroxysmal Nocturnal Hemoglobinuria (PNH); Persistent Anemia

Keywords

C5 inhibitor; Complement Factor B (CFB) protein; Red Blood Cells

Outcome Measures

Primary Outcomes (2)

• Occurrence of Treatment-Emergent Adverse Events (TEAEs)

  Through 365 Days

• Severity of TEAEs

  Through 365 Days

Secondary Outcomes (4)

• 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

Study Arms (2)

Single-Ascending Dose Escalation

EXPERIMENTAL

Drug: ALN-CFB

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

ALN-CFB DRUG

Administered as defined in the protocol

Single-Ascending Dose Escalation

Placebo DRUG

Administered as defined in the protocol

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (7)

Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

RECRUITING

St. Vincent Hospital - The Catholic University of Korea

Suwon, Gyeonggi-do, 16247, South Korea

RECRUITING

Seoul National University Hospital

Seoul, 03080, South Korea

RECRUITING

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, 06591, South Korea

RECRUITING

Severance Hospital

Seoul, 3722, South Korea

RECRUITING

Samsung Medical Center

Seoul, 6351, South Korea

RECRUITING

St. James's University Hospital

Leeds, West Yorkshire, LS97TF, United Kingdom

RECRUITING

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Clinical Trials Administrator

CONTACT

844-734-6643; clinicaltrials@regeneron.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2025
• First Posted: September 23, 2025
• Study Start: February 11, 2026
• Primary Completion (Estimated): November 29, 2029
• Study Completion (Estimated): July 15, 2031
• Last Updated: March 17, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• 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
• 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

Locations

GB (1); KR (5); CA (1)