Safety, Tolerability, PK and PD of ADX-038 in Healthy Participants and Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria (PNH)
- Interventions
- Drug: Placebo
- Registration Number
- NCT05876312
- Lead Sponsor
- ADARx Pharmaceuticals, Inc.
- Brief Summary
The first-in-human Phase 1/Phase 2a study described herein will evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of ADX-038 in both healthy participants (HP) and in patients with paroxysmal nocturnal hemoglobinuria (PNH).
- Detailed Description
The clinical study described in this protocol is a Phase 1/Phase 2a study evaluating safety, tolerability, PK, and PD of ADX-038.
The study consists of 2 parts:
1. Phase 1 - Randomized, double-blind, placebo-controlled, parallel group, single ascending dose (SAD) in HP with up to 5 dose cohorts.
2. Phase 2a - Open label, single-arm (ADX-038), 2 dose study in participants with paroxysmal nocturnal hemoglobinuria (PNH) and residual anemia on a standard-of-care (SOC) anti-C5 regimen of ravulizumab or eculizumab.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 50
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Phase 1 - Active ADX-038 administered to HP ADX-038 For each cohort in Phase 1 (SAD), 8 participants will be randomized in a 3:1 ratio; 6 participants to active (ADX-038): 2 participants to control (matched placebo). Randomization will be on Day 1. Initially, 2 sentinel participants (1 active and 1 placebo) will be randomized and dosed. The sentinel participants will be evaluated for safety. The investigator's assessment and the independent medical monitor will decide upon the randomization and dosing of the 6 remaining participants (5 active and 1 placebo) according to the randomization schedule. Phase 1- Placebo administered to HP Placebo For each cohort in Phase 1 (SAD), 8 participants will be randomized in a 3:1 ratio; 6 participants to active (ADX-038): 2 participants to control (matched placebo). Randomization will be on Day 1. Initially, 2 sentinel participants (1 active and 1 placebo) will be randomized and dosed. The sentinel participants will be evaluated for safety. The investigator's assessment and the independent medical monitor will decide upon the randomization and dosing of the 6 remaining participants (5 active and 1 placebo) according to the randomization schedule. Phase 2a - ADX-038 administered to PNH participants ADX-038 This will be initiated at the dose level determined by the Safety Review Committee from SAD in HPs. The treatment of PNH participants is an open-label study.
- Primary Outcome Measures
Name Time Method Safety in Healthy Volunteers 365 days To evaluate the safety and tolerability of ADX-038 in HVs by incidence, relationship, and severity of adverse events and serious adverse events
Safety in Paroxysmal Nocturnal Hemoglobinuria Participants 365 days Evaluate the safety and tolerability of ADX-038 by incidence, relationship, and treatment-emergent adverse events and serious adverse events.
- Secondary Outcome Measures
Name Time Method Pharmacokinetics in Healthy Participants 8 days To characterize the Pharmacokinetics of ADX-038 in HPs by measuring the Maximum observed plasma concentration (Cmax)
Pharmacodynamics in Healthy Participants 365 days Change in complement alternative pathway activity via assay measurement
Pharmacodynamics in Paraxysmal Nocturnal Hemoglobinuria 365 days Characterize the changes in serum concentration of complement factor B (CFB) protein and complement alternative pathway activity level.
Trial Locations
- Locations (4)
Richmond Pharmacology Ltd
🇬🇧London, United Kingdom
Nucleus Network Brisbane
🇦🇺Brisbane, Queensland, Australia
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia