Safety, Tolerability, PK, and PD of ADX-038 in Healthy Volunteers and Patients with PNH
Research type
Research Study
Full title
A Phase 1, Randomized, Placebo-Controlled, Double Blind Single Ascending Dose Study in Healthy Volunteers Followed by Open Label Treatment in Patients with Paroxysmal Nocturnal Hemoglobinuria to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ADX-038
IRAS ID
1009560
Contact name
Christopher Claeboe
Contact email
Sponsor organisation
ADARx Pharmaceuticals, Inc.
Clinicaltrials.gov Identifier
Research summary
Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare, life-threatening blood disorder. It is characterised by a chronic breakdown of blood cells and is associated with bone marrow failure, blood clot formation and kidney impairment. It is caused by a genetic mutation, leading to disruption of the complement pathway, a system that helps to control the immune system. Current treatment approaches for the condition are extremely limited.
The purpose of this study is to evaluate the safety and efficacy of ADX-038 in healthy volunteers and participants with PNH. ADX-038 is a small interfering RNA (siRNA) oligonucleotide, delivered by subcutaneous injection, intended for the treatment of PNH and other similar diseases. It limits the activity of part of the complement pathway (the alternative pathway) by stopping a gene from making a protein called complement factor B (CFB).
In Part A, up to 40 healthy volunteers will be enrolled. Participants will have a 3:1 chance to receive a single dose of either ADX-038 or placebo in cohorts of eight participants. As a double-blind study, neither the study doctor nor the participants know which treatment they receive, and the treatments will be randomly assigned. Part B will be open label, with no placebo, involving 2-10 participants with PNH. Participants will be followed up until CFB levels return to ≥80% of baseline, or the alternative pathway activity returns to ≥50% of baseline, up to 365 days.
Prior to enrolment, participants will be assessed to ensure they are safe to dose. The primary risk is from infection due to the inhibition of the complement system. While ADX-038 limits this risk by being selective for the alternative complement pathway, participants will need to have evidence of required vaccinations before being enrolled. They will also receive prophylactic antibiotics from the day before dosing until a point determined by the research doctor based on emerging data from the study.
REC name
South Central - Berkshire Research Ethics Committee
REC reference
24/SC/0064
Date of REC Opinion
2 May 2024
REC opinion
Further Information Favourable Opinion