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
Trial Snapshot
- Phase
- Phase 1
- Status
- Active, not recruiting
- Sponsor
- ADARx Pharmaceuticals, Inc.
- Enrollment
- 53
- Locations
- 2
- Primary Endpoint
- Safety in Hereditary Angioedema
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Masking Description
Double blinded
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Part A - HV
- •Inclusion Criteria:
- •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
Exclusion Criteria
- •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
- •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.
- •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
- •Inclusion Criteria:
- •Male and female ≥18 years old, inclusive, at the time of signing the PICF
- •Confirmed diagnosis of HAE Types I or II
- •Evidence of an average of (at least) one HAE attack per month
- •Participants must have access to, and the ability to use, acute medication(s) to treat angioedema attacks.
- •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
- •Exclusion Criteria:
- •Concurrent diagnosis of any other type of chronic angioedema
- •History of clinically significant arterial or venous thrombosis, or current history of a clinically significant prothrombotic risk.
- •Any significant medical history
- •Active malignancy and/or history of malignancy in the past 5 years
- •Any active infection or acute illness, inclusive of cold/flu or COVID-19, within 30 days prior to the first study drug administration.
- •Major surgery or significant traumatic injury occurring within 3 months prior to signature of the PICF
- •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.
- •Positive serology tests for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV).
- •Use of C1-INH products, androgens, antifibrinolytics or other small molecule medications for routine prophylaxis within four half-lives prior to screening
- •Must have documented evidence of medical history of HAE attacks
- •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.
- •Treatment with another investigational product or biologic agent within 30 days prior to the study drug administration
- •History or presence of alcohol abuse or drug use within 30 days prior to the first study drug administration and throughout the study.
- •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.
- •Pregnancy, intent to become pregnant during the course of the study, or lactating women.
Arms & Interventions
PART B - ADX-324 administered to HAE participants
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.
Intervention: ADX-324 (Drug)
PART A- Placebo administered to HV
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.
Intervention: Placebo (Drug)
PART A - Active ADX-324 administered to HV
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.
Intervention: ADX-324 (Drug)
Outcomes
Primary Outcomes
Safety in Hereditary Angioedema
Time Frame: 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
Safety in Healthy Volunteers
Time Frame: 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
Secondary Outcomes
- Pharmacokinetics in Healthy Volunteers(8 days)
- Pharmacodynamics in Healthy Volunteers(365 days)
- Pharmacokinetics in Hereditary Angioedema(8 days)
- Pharmacodynamics in Hereditary Angioedema(365 days)
- Pharmacokinetics in Hereditary Angioedema(365 days)