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
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: ALN-CFB, Placebo.
- Who it may be relevant to
- Registry conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH), Persistent Anemia. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Canada, South Korea, United Kingdom
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
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
Overview
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.
Interventions
- Drug ALN-CFB
Administered as defined in the protocol - Drug Placebo
Administered as defined in the protocol
Primary outcome measures
- Occurrence of Treatment-Emergent Adverse Events (TEAEs) [Time frame: Through 365 Days]
- Severity of TEAEs [Time frame: Through 365 Days]
Secondary outcome measures (4)
- Concentrations of combined ALN-CFB and major metabolites in plasma [Time frame: Through 365 Days]
- Concentrations of combined ALN-CFB and major metabolites in urine [Time frame: Through 24 Hours following ALN-CFB administration]
- Absolute change from baseline in CFB concentration [Time frame: Baseline, Through 365 Days]
- Percentage change from baseline in CFB concentration [Time frame: Baseline, Through 365 Days]
Eligibility criteria
Inclusion criteria
- 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 criteria
- 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
NOTE: Other Protocol Defined Inclusion / Exclusion Criteria Apply
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Sequential
- Masking
- Quadruple blind
- Primary purpose
- Treatment
Study locations
South Korea · 5 centers
- St. Vincent Hospital - The Catholic University of Korea — Suwon
- The Catholic University of Korea, Seoul St. Mary's Hospital — Seoul
- Seoul National University Hospital — Seoul
- Severance Hospital — Seoul
- Samsung Medical Center — Seoul
United Kingdom · 2 centers
- St. James's University Hospital — Leeds
- Kings College Hospital NHS Foundation Trust — London
Canada · 1 center
- Toronto General Hospital — Toronto
Identifiers
NCT: NCT07187401 · ALN-CFB-PNH-2468 · 2024-519806-11-00