Evaluating ADX-038 for safety and effectiveness in healthy individuals and PNH patients

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

This study is testing a new drug called ADX-038 to see if it's safe and effective for healthy people and those with paroxysmal nocturnal hemoglobinuria who still have anemia despite treatment.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: ADARx Pharmaceuticals, Inc. (Industry-sponsored)
• Drugs / interventions: ravulizumab, eculizumab
• Locations: 4 sites (Brisbane, Queensland and 3 other locations)
• Trial ID: NCT05876312 on ClinicalTrials.gov

What this trial studies

This clinical trial is a Phase 1/Phase 2a evaluation of ADX-038, focusing on its safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) in both healthy participants and patients with paroxysmal nocturnal hemoglobinuria (PNH). The study is divided into two parts: a Phase 1 randomized, double-blind, placebo-controlled trial assessing single ascending doses in healthy individuals, and a Phase 2a open-label study in PNH patients who have residual anemia despite standard-of-care treatment. The trial aims to gather comprehensive data on the drug's effects and safety profile.

Who should consider this trial

Good fit: Ideal candidates for this study include healthy adults aged 18 to 55 and patients with paroxysmal nocturnal hemoglobinuria who have residual anemia on standard anti-C5 therapy.

Not a fit: Patients with significant medical conditions, recent infections, or those who do not meet the inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients with paroxysmal nocturnal hemoglobinuria, potentially improving their anemia management.

How similar studies have performed: Other studies have shown promise with similar approaches in treating PNH, but this specific intervention is novel.

Eligibility criteria

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

Where this trial is running

Brisbane, Queensland and 3 other locations

• Nucleus Network Brisbane — Brisbane, Queensland, Australia (Active_not_recruiting)
• Peter MacCallum Cancer Centre — Melbourne, Victoria, Australia (Not_yet_recruiting)
• Royal Melbourne Hospital — Parkville, Victoria, Australia (Recruiting)
• Richmond Pharmacology Ltd — London, United Kingdom (Active_not_recruiting)

Study contacts

• Study coordinator: Lyle Gee

Conditions Paroxysmal Nocturnal Hemoglobinuria; siRNA; PNH