A Phase 1, Randomized, Double Blind, Placebo-Controlled, Single Ascending Dose Study in Healthy Participants Followed by a Phase 2a Open Label Study in Participants With PNH and Residual Anemia to Evaluate the Safety, Tolerability, PK and PD of ADX-038
| Registry | NCT05876312, acronym PNH |
|---|---|
| Status | Recruiting |
| Phase | Phase 1 / Phase 2 |
| Study type | Interventional; randomized, parallel, masking: triple, treatment |
| Enrollment | 50 (Estimated) |
| Sponsor | ADARx Pharmaceuticals, Inc. (Industry); collaborators: ADARx Australia Pty Ltd, Novotech (Australia) Pty Limited |
| Conditions | Paroxysmal Nocturnal Hemoglobinuria (PNH) |
| Interventions | ADX-038, Placebo (Drug) |
| Dates | start 2023-08-07, primary completion 2028-03-31 (estimated), completion 2028-07-31 (estimated), first posted 2023-05-25, last updated 2026-06-16 |
| Locations | 4 sites in Australia, United Kingdom |
Related Papers Related Patents Related Grants Related Experts
All trials for Paroxysmal Nocturnal Hemoglobinuria (PNH) All trials of ADX-038 All trials of Placebo
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).
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.
| Arm | Type | Interventions | Description |
|---|---|---|---|
| Phase 1 - Active ADX-038 administered to HP | Experimental | Drug: 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 comparator | Drug: 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 | Experimental | Drug: 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. |
Sex: All, ages: 18 Years to any, accepts healthy volunteers
Phase 1 Key Inclusion Criteria * 18 to 55 years of age * Participants who are healthy as determined by medical evaluation * History of recent meningococcal, pneumococcal and Haemophilus influenzae type B vaccinations or willing to be vaccinated * Screening tests negative for illicit drug, nicotine, and alcohol use Phase 1 Key Exclusion Criteria * History of any significant medical conditions, except for completely excised non-melanoma skin cancer or low grade cervical intraepithelial neoplasia without evidence of recurrence within the prior 3 months * Any viral, bacterial, parasitic, or fungal infection within the prior 30 days * Frequent respiratory, nasopharyngeal or ear infections (more than 5 infections per year) * History of environmental exposure or sick contact that increase the risk of meningococcal, pneumococcal and/or Haemophilus influenza type B infections * Complement deficiency or immunodeficiency syndrome * Major surgery or significant traumatic injury within the prior 3 months * History of anaphylaxis or hypersensitivity reactions * History of penicillin allergy * History of splenectomy * History of alcohol abuse or illicit drug use * Donated plasma within the prior 7 days * Donated blood or loss more than 400 milliliters of blood (excluding blood volume drawn at screening) within the prior 90 days * Screening estimated creatinine clearance of less than 60 milliliters per minute * Screening hematology, serum chemistry, or coagulation parameters that are outside the normal range * Screening vital signs that are abnormal per protocol specification * Screening electrocardiogram findings that are clinically significant * Pregnant or lactating females * Use of prescription (except for contraceptives and study-related prophylactic antibiotics) or over-the counter medications (except for paracetamol or ibuprofen) or vitamins/supplements within the prior 7 days * Use of medications that may reduce the effectiveness of hormonal contraceptives within the prior 28 days * Use of an investigational therapeutics within the prior 30 days or within the expected washout (at least 5 half-lives) * Unwilling or unable to adhere to study-related prophylactic antibiotics requirements Phase 2a Key Inclusion Criteria * at least 18 years of age * Diagnosis of paroxysmal nocturnal hemoglobinuria based on documented clone size * Hemoglobin concentration of less than 12 gram per deciliter * History of recent meningococcal, pneumococcal and Haemophilus influenzae type b vaccinations or willing to be vaccinated * On a stable anti-C5 regimen for greater than or equal to 12 weeks prior to Day 1 Phase 2a Key Exclusion Criteria * Any viral, bacterial, parasitic, or fungal infection within the prior 14 days * HIV, active hepatitis C or hepatitis B infection * History of meningococcal or tuberculosis infection * History of malignancy in the past 5 years, except for completely excised non-melanoma skin cancer or low grade cervical intraepithelial neoplasia with no evidence of recurrence within the prior 3 months * Complement deficiency syndrome * History of hematopoietic stem cell transplantation * History of splenectomy * Inflammatory bowel disease, systemic lupus erythematosus, rheumatoid arthritis, or chronic liver disease * Clinically significant and uncontrolled medical conditions including, but not limited to, thromboembolic disease, acute coronary syndrome, and diabetes * Pregnant or lactating females * Use of an investigational therapeutics within the prior 30 days or within the expected washout period (at lest 5 half-lives) * Abstain from alcohol consumption for 48 hrs before day of dosing and restrict to no more than an average of 14 standard drinks per week
| Facility | City | Country | Status |
|---|---|---|---|
| Nucleus Network Brisbane | Brisbane, Queensland | Australia | Completed |
| Peter MacCallum Cancer Centre | Melbourne, Victoria | Australia | Completed |
| Royal Melbourne Hospital | Parkville, Victoria | Australia | Recruiting |
| Richmond Pharmacology Ltd | London, London | United Kingdom | Completed |