NCT05876312

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).

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
50

participants targeted

Target at P50-P75 for phase_1

Timeline
28mo left

Started Aug 2023

Longer than P75 for phase_1

Geographic Reach
2 countries

4 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress55%
Aug 2023Jul 2028

First Submitted

Initial submission to the registry

May 17, 2023

Completed
8 days until next milestone

First Posted

Study publicly available on registry

May 25, 2023

Completed
2 months until next milestone

Study Start

First participant enrolled

August 7, 2023

Completed
4.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 31, 2028

Expected
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 31, 2028

Last Updated

April 22, 2026

Status Verified

April 1, 2026

Enrollment Period

4.7 years

First QC Date

May 17, 2023

Last Update Submit

April 20, 2026

Conditions

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Keywords

siRNAPNH

Outcome Measures

Primary Outcomes (2)

  • Safety in Healthy Volunteers

    To evaluate the safety and tolerability of ADX-038 in HVs by incidence, relationship, and severity of adverse events and serious adverse events

    365 days

  • Safety in Paroxysmal Nocturnal Hemoglobinuria Participants

    Evaluate the safety and tolerability of ADX-038 by incidence, relationship, and treatment-emergent adverse events and serious adverse events.

    365 days

Secondary Outcomes (5)

  • Pharmacokinetics in Healthy Participants

    8 days

  • Pharmacodynamics in Healthy Participants

    365 days

  • Pharmacodynamics in Paraxysmal Nocturnal Hemoglobinuria

    365 days

  • Pharmacodynamics in Paraxysmal Nocturnal Hemoglobinuria

    365 days

  • Pharmacodynamics in Healthy Participants

    365 days

Other Outcomes (17)

  • Immune Response in Healthy Participants

    365 days

  • Pharmacodynamics in Healthy Participants

    365 days

  • Safety in Paroxysmal Nocturnal Hemoglobinuria Participants

    365 days

  • +14 more other outcomes

Study Arms (3)

Phase 1 - Active ADX-038 administered to HP

EXPERIMENTAL

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.

Drug: ADX-038

Phase 1- Placebo administered to HP

PLACEBO COMPARATOR

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.

Drug: Placebo

Phase 2a - ADX-038 administered to PNH participants

EXPERIMENTAL

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.

Drug: ADX-038

Interventions

ADX-038DRUG

siRNA duplex oligonucleotide

Also known as: siRNA
Phase 1 - Active ADX-038 administered to HPPhase 2a - ADX-038 administered to PNH participants
PlaceboDRUG

Saline

Also known as: Saline
Phase 1- Placebo administered to HP

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • +23 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Nucleus Network Brisbane

Brisbane, Queensland, 4006, Australia

ACTIVE NOT RECRUITING

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

NOT YET RECRUITING

Royal Melbourne Hospital

Parkville, Victoria, 3052, Australia

RECRUITING

Richmond Pharmacology Ltd

London, SE1 1YR, United Kingdom

ACTIVE NOT RECRUITING

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal

Interventions

RNA, Small InterferingSodium Chloride

Condition Hierarchy (Ancestors)

Anemia, HemolyticAnemiaHematologic DiseasesHemic and Lymphatic DiseasesMyelodysplastic SyndromesBone Marrow Diseases

Intervention Hierarchy (Ancestors)

RNA, AntisenseAntisense Elements (Genetics)Nucleic Acids, Nucleotides, and NucleosidesRNANucleic AcidsRNA, Small UntranslatedRNA, UntranslatedChloridesHydrochloric AcidChlorine CompoundsInorganic ChemicalsSodium Compounds

Central Study Contacts

Lyle Gee

CONTACT

877-232-7974lgee@adarx.com

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Masking Details
Masking is only applicable to Phase 1 in HP. Phase 2a is open label and there is no masking.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Model Description
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 17, 2023

First Posted

May 25, 2023

Study Start

August 7, 2023

Primary Completion (Estimated)

March 31, 2028

Study Completion (Estimated)

July 31, 2028

Last Updated

April 22, 2026

Record last verified: 2026-04

Data Sharing

IPD Sharing
Will not share

Locations

GB(1)AU(3)