Safety, Tolerability, PK, PD of ADX-324 in Healthy Volunteers and Hereditary Angioedema Patients

NCT05691361 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: ADX-324-101
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief Summary

The first-in-human Phase 1 study will evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of ADX-324 in healthy volunteers (HV) and in patients with Hereditary Angioedema (HAE).

Conditions

Hereditary Angioedema

Outcome Measures

Primary Outcomes (3)

• Safety in Healthy Volunteers

  To evaluate the safety and tolerability of ADX-324 in HVs by incidence, relationship, and severity of adverse events and serious adverse events

  365 days

• Safety in Healthy Volunteers

  To evaluate the safety and tolerability of ADX-324 in HVs by change in baseline electrocardiogram (ECG) parameters (PR, QRS, QT, and QTcF intervals)

  365 days

• Safety in Hereditary Angioedema

  To evaluate the safety and tolerability of ADX-324 in HAE by incidence, relationship, and severity of adverse events and serious adverse events

  365 days

Secondary Outcomes (20)

• Pharmacokinetics in Healthy Volunteers

  8 days

• Pharmacokinetics in Healthy Volunteers

  8 days

• Pharmacokinetics in Healthy Volunteers

  8 days

• Pharmacokinetics in Healthy Volunteers

  8 days

• Pharmacokinetics in Healthy Volunteers

  8 days

Study Arms (3)

PART A - Active ADX-324 administered to HV

EXPERIMENTAL

For each cohort in Part A (SAD), 8 participants will be randomized in a 3:1 ratio; 6 participants to active (ADX-324): 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-324

PART A- Placebo administered to HV

PLACEBO COMPARATOR

For each cohort in Part A (SAD), 8 participants will be randomized in a 3:1 ratio; 6 participants to active (ADX-324): 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

PART B - ADX-324 administered to HAE participants

EXPERIMENTAL

This will be initiated at the dose level determined by the Safety Review Committee from SAD in HVs. The treatment of HAE participants is an open-label study.

Drug: ADX-324

Interventions

ADX-324 DRUG

siRNA duplex oligonucleotide

Also known as: siRNA

PART A - Active ADX-324 administered to HV; PART B - ADX-324 administered to HAE participants

Placebo DRUG

saline

Also known as: Saline

PART A- Placebo administered to HV

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male and female adults 18 to 55 years old
• Body mass index (BMI) between 18 and 30 kg/m2
• Contraception use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
• Willing and able to provide informed consent and comply with all study visits

You may not qualify if:

• Any significant medical history
• Active malignancy and/or history of malignancy in the past 5 years
• History of liver disease, Gilbert's syndrome, or abnormal liver function test
• Estimated creatinine clearance \<60 mL/min or serum creatinine \> 1.5-fold upper limit of normal.
• Any active infection or acute illness
• Major surgery or significant traumatic injury occurring within 3 months
• Positive serology tests (HepB, Hep C, HIV)
• Use of any prescription, vaccines, supplements/vitamins, or over-the counter medication
• Treatment with another investigational product within 30 days prior to the first study drug administration
• Known any clinically significant allergic reactions which, in the opinion of the Investigator, would interfere with the volunteer's ability to participate in the study
• Known hypersensitivity to any of the study drug ingredients.
• Pregnancy, intent to become pregnant during the course of the study, or lactating women
• Part B - HAE
• Male and female ≥18 years old, inclusive, at the time of signing the PICF
• Confirmed diagnosis of HAE Types I or II

Sponsors & Collaborators

• ADARx Pharmaceuticals, Inc.: lead
• Avance Clinical Pty Ltd.: collaborator

Study Sites (1)

CMAX Clinical Research

Adelaide, South Australia, 5000, Australia

Location

MeSH Terms

Conditions

Angioedemas, Hereditary

Interventions

RNA, Small Interfering; Sodium Chloride

Condition Hierarchy (Ancestors)

Angioedema; Vascular Diseases; Cardiovascular Diseases; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Immunologic Deficiency Syndromes

Intervention Hierarchy (Ancestors)

RNA, Antisense; Antisense Elements (Genetics); Nucleic Acids, Nucleotides, and Nucleosides; RNA; Nucleic Acids; RNA, Small Untranslated; RNA, Untranslated; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Lauge Farnaes, MD

  ADARx Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double blinded
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1, Single-Center, Randomized, Placebo-Controlled, Double Blind Single Ascending Dose Study in HV with expansion into HAE

Study Record Dates

• First Submitted: December 16, 2022
• First Posted: January 20, 2023
• Study Start: December 14, 2022
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 27, 2026

Record last verified: 2026-04

Locations

AU (1)