ClinicalTrials.gov record NCT05876312

Safety, Tolerability, PK and PD of ADX-038 in Healthy Participants and Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients

Record copied from ClinicalTrials.gov: Oct 10, 2026AI summaries generated: Jul 27, 2026

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

StatusRecruitingThe study is currently enrolling participants. Only the study team can say whether a particular person can join.
Study typeInterventionalA study in which researchers assign participants to one or more interventions, such as a drug, procedure, device, behavioural programme or other approach, to measure their effects.
PhasePhase 1/2A study that combines safety and dose-finding (phase 1) with a first look at whether the treatment has an effect (phase 2).
Healthy volunteersAcceptedPeople who do not have the condition being studied who are allowed to take part. Some studies include both people with the condition and healthy volunteers; others may enrol only healthy volunteers.
Age18 years old and older
SexAll
LocationAustralia, United Kingdom
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

This first-in-human Phase 1/2a study evaluates the siRNA drug ADX-038. Phase 1 gives single ascending doses to healthy adults in a randomized, blinded, placebo-controlled design; Phase 2a is an open-label, two-dose study in adults with PNH and residual anemia who are on stable anti-C5 therapy.

What it is studying. The study is testing the safety and tolerability of the siRNA drug ADX-038, how the body absorbs and clears it (pharmacokinetics), and how it affects biological targets (pharmacodynamics) such as complement factor B and hemoglobin levels.

What the researchers hope to learn. To evaluate safety and tolerability of ADX-038; to characterize pharmacokinetics (e.g., Cmax) and pharmacodynamics including changes in complement factor B, complement alternative pathway activity, and hemoglobin in PNH participants.

What this study is about

The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.

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).

Interventions being studied

Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.

Drug
  • ADX-038
  • Placebo

Eligibility

The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.

Inclusion 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

Study description and what participation involves

The study's detailed description, as published on ClinicalTrials.gov.

Detailed description from the registry

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:

  • Phase 1 - Randomized, double-blind, placebo-controlled, parallel group, single ascending dose (SAD) in HP with up to 5 dose cohorts.
  • 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.
AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

Phase 1 (healthy volunteers) involves a single ascending dose: participants are randomized to receive ADX‑038 or matched placebo, with two sentinel participants dosed first and close safety monitoring before dosing others. Phase 2a (PNH participants) is open‑label and uses the dose chosen from Phase 1; participants remain on their standard anti‑C5 therapy. Both parts include medical exams, safety assessments, and repeated blood sampling for pharmacokinetics and pharmacodynamics (including measurements of complement factor B, complement activity, and hemoglobin), plus follow‑up visits and adverse‑event monitoring for up to about 1 year. Participants should expect vaccination or agreement to be vaccinated, possible prophylactic antibiotics, pregnancy testing/contraception requirements, and restrictions on recent blood/plasma donation, certain medications, and alcohol use around dosing.

How the study is structured. Phase 1: randomized, blinded, placebo-controlled, single-ascending-dose (SAD) cohorts in healthy adults. Phase 2a: open-label, single-arm, two-dose study in adults with PNH who remain anemic while on stable anti-C5 treatment.

Questions you could ask

These questions are suggestions for a conversation with the study team or your own clinician, not advice.

  • Some participants receive a placebo. How is that decided, and what happens for placebo-group participants when the study ends?
  • This is an early-phase study, mainly about safety and dose. What is already known about this treatment?
  • The listed sites are in Australia, United Kingdom. Is any of them reachable for me, and does the study help with travel?
  • Which of the eligibility criteria would need to be checked with tests before I could join?

More on paroxysmal nocturnal hemoglobinuria

Clinical trials44 trials listed for paroxysmal nocturnal hemoglobinuriaEvery trial the registry lists for paroxysmal nocturnal hemoglobinuria, with recruitment status, phase and sites, updated from ClinicalTrials.gov.See all trials →Research updatesWhat changed in paroxysmal nocturnal hemoglobinuria researchLatest monthly update: September 2026. Includes: Treatment access. New research summarized each month in plain language, with links to every source paper.Read the latest update →

Important dates

Study start
Aug 7, 2023
Primary completion
Mar 31, 2028 (estimated)
Study completion
Jul 31, 2028 (estimated)
Target enrollment
50 participants (estimated)
Last updated on registry
Jun 16, 2026
Data verified
Oct 10, 2026

Sponsor and research team

The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.

Lead sponsor
ADARx Pharmaceuticals, Inc.
Collaborators
  • ADARx Australia Pty Ltd
  • Novotech (Australia) Pty Limited

Central study contact

If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.

Participating sites (4)

  • Nucleus Network BrisbaneCompleted

    Brisbane, Queensland, 4006 · Australia

  • Peter MacCallum Cancer CentreCompleted

    Melbourne, Victoria, 3000 · Australia

  • Royal Melbourne HospitalRecruiting

    Parkville, Victoria, 3052 · Australia

  • Richmond Pharmacology LtdCompleted

    London, London, SE1 1YR · United Kingdom

Terms used on this page · explanations by MedicalUpdates.ai

first-in-human
The first study in which a treatment is given to people. Safety is the main question and the number of participants is usually small.
Phase 1
An early-stage study, usually small, mainly to check safety, side effects and how much of a treatment can be given. Whether it works is not the main question yet.
pharmacokinetics
How the body absorbs, distributes, breaks down and removes a drug. It is studied by measuring drug levels or related substances at set times after a dose.
pharmacodynamics
What a drug does to the body, for example how it changes a blood marker or a symptom, and how that relates to the dose.
Key Inclusion Criteria
The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
at screening
The checks done before enrolment to see whether a person qualifies, such as tests, scans or a review of medical history.
creatinine clearance
A measure of kidney function, calculated from a blood creatinine level together with age, weight and sex.
electrocardiogram
A recording of the heart's electrical activity. QTc is one measurement from it; some drugs are avoided if it is prolonged.
investigational
A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
washout
A period during which a participant stops a previous treatment before starting the study treatment, so the earlier treatment does not affect the results.
5 half-lives
The time it takes for the amount of a drug in the body to fall by half. 'Five half-lives' is often used as the point at which a previous drug has essentially left the body.
Key Exclusion Criteria
The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
Randomized
Participants are assigned to the study groups by chance, like a coin toss, rather than chosen by the doctor or the participant. This is done so the groups are comparable.
double-blind
Two types of people involved in the study do not know which intervention a participant is receiving. The ClinicalTrials.gov record specifies who is masked, for example participants, care providers, investigators or outcome assessors.
placebo-controlled
A study design in which one group receives a placebo so that the study treatment's effects can be compared with no active treatment.
parallel group
Participants are divided into two or more groups, and each group receives a different intervention at the same time, so the groups can be compared.
ascending dose
Groups of participants receive increasing doses of a treatment, one group after another, to find a dose that can be given safely.
Open label
No masking is used, so the assigned intervention is not deliberately hidden from participants or study staff.
single-arm
All participants receive the same treatment or follow the same plan. There is no comparison group within the study.

The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.

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