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

PHASE1RECRUITING

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).

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Study details:

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.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

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

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

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

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

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

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Eligibility

Age eligible for study : 18 and older

Healthy volunteers accepted : Yes

Gender eligible for study: All

Things to know

Study dates

Study start: 2022-12-14

Primary completion: 2025-01-02

Study completion finish: 2025-12-26

Study type

TREATMENT

Phase

PHASE1

Trial ID

NCT05691361

Intervention or treatment

DRUG: ADX-324

DRUG: Placebo

Conditions

• Hereditary Angioedema

Condition: Hereditary Angioedema
DRUG: ADX-324 and other drugs
Adelaide, South Australia, Australia
Sponsor: ADARx Pharmaceuticals, Inc.

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Find a site

Closest Location:

CMAX Clinical Research

Research sites nearby

Select from list below to view details:

CMAX Clinical Research
Adelaide, South Australia, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: 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.	DRUG: ADX-324 siRNA duplex oligonucleotide
PLACEBO_COMPARATOR: 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.	DRUG: Placebo saline
EXPERIMENTAL: 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.	DRUG: ADX-324 siRNA duplex oligonucleotide

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
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 outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
Pharmacokinetics in Healthy Volunteers	To characterize the Pharmacokinetics of ADX-324 in HVs by measuring the Maximum observed concentration (Cmax)	8 days
Pharmacokinetics in Healthy Volunteers	To characterize the Pharmacokinetics of ADX-324 in HVs by measuring the Time to Cmax (Tmax)	8 days
Pharmacokinetics in Healthy Volunteers	To characterize the Pharmacokinetics of ADX-324 in HVs by measuring the Area under the concentration-time curve from 0 to time of last quantifiable concentration (AUC0-last)	8 days
Pharmacokinetics in Healthy Volunteers	To characterize the Pharmacokinetics of ADX-324 in HVs by measuring the Area under the concentration-time curve from 0 to infinity (AUC0-∞)	8 days
Pharmacokinetics in Healthy Volunteers	To characterize the Pharmacokinetics of ADX-324 in HVs by measuring the Apparent terminal half-life (t½)	8 days
Pharmacokinetics in Healthy Volunteers	To characterize the Pharmacokinetics of ADX-324 in HVs by measuring the Terminal elimination rate constant (λz)	8 days
Pharmacokinetics in Healthy Volunteers	To characterize the Pharmacokinetics of ADX-324 in HVs by measuring the Total apparent body clearance (CL/F)	8 days
Pharmacokinetics in Healthy Volunteers	To characterize the Pharmacokinetics of ADX-324 in HVs by measuring the Apparent volume of distribution (Vz/F)	8 days
Pharmacodynamics in Healthy Volunteers	To characterize the PD of ADX-324 in HVs by the Change from base in plasma concentrations over time of pre Kallikrein (PKK)	365 days
Pharmacodynamics in Healthy Volunteers	To characterize the PD of ADX-324 in HVs by the Change from base in plasma concentrations over time of Kallikrein (KK)	365 days
Pharmacokinetics in Hereditary Angioedema	To characterize the PD of ADX-324 in HAE by Maximum observed concentration (Cmax) of ADX-324	365 days
Pharmacokinetics in Hereditary Angioedema	To characterize the PD of ADX-324 in HAE by Time to Cmax (Tmax) of ADX-324	8 days
Pharmacokinetics in Hereditary Angioedema	To characterize the PD of ADX-324 in HAE by Area under the concentration-time curve from 0 to time of last quantifiable concentration (AUC0-last) of ADX-324	8 days
Pharmacokinetics in Hereditary Angioedema	To characterize the PD of ADX-324 in HAE by Area under the concentration-time curve from 0 to infinity (AUC0-∞) of ADX-324	8 days
Pharmacokinetics in Hereditary Angioedema	To characterize the PD of ADX-324 in HAE by Apparent terminal half-life (t½)	8 days
Pharmacokinetics in Hereditary Angioedema	To characterize the PD of ADX-324 in HAE by Terminal elimination rate constant (λz)	8 days
Pharmacokinetics in Hereditary Angioedema	To characterize the PD of ADX-324 in HAE by Total apparent body clearance (CL/F)	8 days
Pharmacokinetics in Hereditary Angioedema	To characterize the PD of ADX-324 in HAE by Apparent volume of distribution (Vz/F)	8 days
Pharmacodynamics in Hereditary Angioedema	To characterize the PD of ADX-324 in HV by Change from base in plasma concentrations over time pre-kallikrein (PKK)	365 days
Pharmacodynamics in Hereditary Angioedema	To characterize the PD of ADX-324 in HAE by Change from base in plasma concentrations over time kallikren (KK)	365 days

Frequently Asked Questions

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References

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