Clinical trial NCT05691361: Safety, Tolerability, PK, PD of ADX-324 in Healthy Volunteers and Hereditary Angioedema Patients
Official title: A Phase 1, Randomized, Placebo-Controlled, Double-Blind Study in Healthy Volunteers and a Phase 2a, Open-Label Study in Patients With Hereditary Angioedema to Evaluate the Safety, Tolerability, PK and PD of ADX-324
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Hereditary Angioedema
Lead sponsor: ADARx Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Avance Clinical Pty Ltd.
First posted: 2023-01-20
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Phase 1, Single-Center, Randomized, Placebo-Controlled, Double Blind Single Ascending Dose Study in HV with expansion into HAE
Primary purpose: TREATMENT

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.

Eligibility 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

Exclusion Criteria:

1. Concurrent diagnosis of any other type of chronic angioedema
2. History of clinically significant arterial or venous thrombosis, or current history of a clinically significant prothrombotic risk.
3. Any significant medical history
4. Active malignancy and/or history of malignancy in the past 5 years
5. Any active infection or acute illness, inclusive of cold/flu or COVID-19, within 30 days prior to the first study drug administration.
6. Major surgery or significant traumatic injury occurring within 3 months prior to signature of the PICF
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 for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV).
9. Use of C1-INH products, androgens, antifibrinolytics or other small molecule medications for routine prophylaxis within four half-lives prior to screening
10. Must have documented evidence of medical history of HAE attacks
11. Use of any prescription, vaccines, supplements/vitamins, or over-the counter medication (with the exception of oral contraceptives) within 7 days prior to the first study drug administration.
12. Treatment with another investigational product or biologic agent within 30 days prior to the study drug administration
13. History or presence of alcohol abuse or drug use within 30 days prior to the first study drug administration and throughout the study.
14. Blood donation of 50 to 499 mL within 30 days prior to the first study drug administration or of \>499 mL within 60 days prior to the first study drug administration.
15. Pregnancy, intent to become pregnant during the course of the study, or lactating women.

Primary outcomes:
measure: Safety in Healthy Volunteers
timeFrame: 365 days
measure: Safety in Healthy Volunteers
timeFrame: 365 days
measure: Safety in Hereditary Angioedema
timeFrame: 365 days
Secondary outcomes:
measure: Pharmacokinetics in Healthy Volunteers
timeFrame: 8 days
measure: Pharmacokinetics in Healthy Volunteers
timeFrame: 8 days
measure: Pharmacokinetics in Healthy Volunteers
timeFrame: 8 days
measure: Pharmacokinetics in Healthy Volunteers
timeFrame: 8 days
measure: Pharmacokinetics in Healthy Volunteers
timeFrame: 8 days
measure: Pharmacokinetics in Healthy Volunteers
timeFrame: 8 days
measure: Pharmacokinetics in Healthy Volunteers
timeFrame: 8 days
measure: Pharmacokinetics in Healthy Volunteers
timeFrame: 8 days
measure: Pharmacodynamics in Healthy Volunteers
timeFrame: 365 days
measure: Pharmacodynamics in Healthy Volunteers
timeFrame: 365 days
measure: Pharmacokinetics in Hereditary Angioedema
timeFrame: 365 days
measure: Pharmacokinetics in Hereditary Angioedema
timeFrame: 8 days
measure: Pharmacokinetics in Hereditary Angioedema
timeFrame: 8 days
measure: Pharmacokinetics in Hereditary Angioedema
timeFrame: 8 days
measure: Pharmacokinetics in Hereditary Angioedema
timeFrame: 8 days
measure: Pharmacokinetics in Hereditary Angioedema
timeFrame: 8 days
measure: Pharmacokinetics in Hereditary Angioedema
timeFrame: 8 days
measure: Pharmacokinetics in Hereditary Angioedema
timeFrame: 8 days
measure: Pharmacodynamics in Hereditary Angioedema
timeFrame: 365 days
measure: Pharmacodynamics in Hereditary Angioedema
timeFrame: 365 days
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: CMAX Clinical Research
state: South Australia
Study officials:
affiliation: CMAX Clinical Research Pty Ltd
name: Nicholas Farinola, MD
role: PRINCIPAL_INVESTIGATOR
References: