Hereditary Angioedema
Conditions
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).
Detailed description
The clinical study described in this protocol is a Phase 1, single-center study evaluating safety, tolerability, PK, and PD of ADX-324. The study consists of 2 parts: * Randomized, double-blind, placebo-controlled, parallel group, single ascending dose (SAD) in HV with up to 6 dose cohorts. For SAD cohorts and planned dosing; and, * Expansion cohort in participants with Hereditary Angioedema (HAE) at selected dose from Part A and will be open label.
Interventions
DRUGADX-324
siRNA duplex oligonucleotide
DRUGPlacebo
saline
Sponsors
ADARx Pharmaceuticals, Inc.
Avance Clinical Pty Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double blinded
Intervention model description
Phase 1, Single-Center, Randomized, Placebo-Controlled, Double Blind Single Ascending Dose Study in HV with expansion into HAE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Part A - HV Inclusion Criteria: 1. Male and female adults 18 to 55 years old 2. Body mass index (BMI) between 18 and 30 kg/m2 3. Contraception use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies 4. Willing and able to provide informed consent and comply with all study visits
Exclusion criteria
1. Any significant medical history 2. Active malignancy and/or history of malignancy in the past 5 years 3. History of liver disease, Gilbert's syndrome, or abnormal liver function test 4. Estimated creatinine clearance \<60 mL/min or serum creatinine \> 1.5-fold upper limit of normal. 5. Any active infection or acute illness 6. Major surgery or significant traumatic injury occurring within 3 months 7. Have any other conditions that, in the opinion of the Investigator or Sponsor, would make the participant unsuitable for inclusion, or could interfere with the participant participating in or completing the study. 8. Positive serology tests (HepB, Hep C, HIV) 9. Use of any prescription, vaccines, supplements/vitamins, or over-the counter medication 10. Treatment with another investigational product within 30 days prior to the first study drug administration 11. 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 12. Known hypersensitivity to any of the study drug ingredients. 13. Pregnancy, intent to become pregnant during the course of the study, or lactating women Part B - HAE Inclusion Criteria: 1. Male and female ≥18 years old, inclusive, at the time of signing the PICF 2. Confirmed diagnosis of HAE Types I or II 3. Evidence of an average of (at least) one HAE attack per month 4. Participants must have access to, and the ability to use, acute medication(s) to treat angioedema attacks. 5. Body mass index (BMI) between 18 and 30 kg/m2 6. Contraception use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies 7. Willing and able to provide informed consent and comply with all study visits
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety in Healthy Volunteers | 365 days | To evaluate the safety and tolerability of ADX-324 in HVs by incidence, relationship, and severity of adverse events and serious adverse events |
| Safety in Hereditary Angioedema | 365 days | To evaluate the safety and tolerability of ADX-324 in HAE by incidence, relationship, and severity of adverse events and serious adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics in Healthy Volunteers | 8 days | To characterize the Pharmacokinetics of ADX-324 in HVs by measuring the Maximum observed concentration (Cmax) |
| Pharmacodynamics in Healthy Volunteers | 365 days | To characterize the PD of ADX-324 in HVs by the Change from base in plasma concentrations over time of pre Kallikrein (PKK) |
| Pharmacokinetics in Hereditary Angioedema | 365 days | To characterize the PD of ADX-324 in HAE by Maximum observed concentration (Cmax) of ADX-324 |
| Pharmacodynamics in Hereditary Angioedema | 365 days | To characterize the PD of ADX-324 in HV by Change from base in plasma concentrations over time pre-kallikrein (PKK) |
Countries
Australia
Contacts
STUDY_DIRECTORLauge Farnaes, MD
ADARx Pharmaceuticals
Outcome results
None listed