Hereditary AngioedemaPhase 1/2NCT05691361
Safety, Tolerability, PK, PD of ADX-324 in Healthy Volunteers and Hereditary Angioedema Patients
A Phase 1/2 study testing ADX-324 in people with Hereditary Angioedema, run by ADARx Pharmaceuticals, Inc. at 1 site in Australia.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Hereditary Angioedema
- What is being tested?
- ADX-324
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 53 participants
- Where
- 1 siteAustralia
- Study dates
- 14 Dec 2022to 31 Dec 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Show all 11Show fewer
- 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
Who cannot join
- 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
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- 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
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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).
Read the 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.
- Conditions
- Hereditary Angioedema
- Being tested
- ADX-324, Placebo
- Medical subject headings
- Angioedemas, Hereditary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ADX-324Drug
Also called siRNA
siRNA duplex oligonucleotide
PlaceboDrug
Also called Saline
saline
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: ADX-324 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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)
Measured: 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
Measured: 365 days
Secondary outcomes (20)
Pharmacokinetics in Healthy Volunteers
To characterize the Pharmacokinetics of ADX-324 in HVs by measuring the Maximum observed concentration (Cmax)
Measured: 8 days
Pharmacokinetics in Healthy Volunteers
To characterize the Pharmacokinetics of ADX-324 in HVs by measuring the Time to Cmax (Tmax)
Measured: 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)
Measured: 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-∞)
Measured: 8 days
Pharmacokinetics in Healthy Volunteers
To characterize the Pharmacokinetics of ADX-324 in HVs by measuring the Apparent terminal half-life (t½)
Measured: 8 days
Pharmacokinetics in Healthy Volunteers
To characterize the Pharmacokinetics of ADX-324 in HVs by measuring the Terminal elimination rate constant (λz)
Measured: 8 days
Pharmacokinetics in Healthy Volunteers
To characterize the Pharmacokinetics of ADX-324 in HVs by measuring the Total apparent body clearance (CL/F)
Measured: 8 days
Pharmacokinetics in Healthy Volunteers
To characterize the Pharmacokinetics of ADX-324 in HVs by measuring the Apparent volume of distribution (Vz/F)
Measured: 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)
Measured: 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)
Measured: 365 days
Pharmacokinetics in Hereditary Angioedema
To characterize the PD of ADX-324 in HAE by Maximum observed concentration (Cmax) of ADX-324
Measured: 365 days
Pharmacokinetics in Hereditary Angioedema
To characterize the PD of ADX-324 in HAE by Time to Cmax (Tmax) of ADX-324
Measured: 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
Measured: 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
Measured: 8 days
Pharmacokinetics in Hereditary Angioedema
To characterize the PD of ADX-324 in HAE by Apparent terminal half-life (t½)
Measured: 8 days
Pharmacokinetics in Hereditary Angioedema
To characterize the PD of ADX-324 in HAE by Terminal elimination rate constant (λz)
Measured: 8 days
Pharmacokinetics in Hereditary Angioedema
To characterize the PD of ADX-324 in HAE by Total apparent body clearance (CL/F)
Measured: 8 days
Pharmacokinetics in Hereditary Angioedema
To characterize the PD of ADX-324 in HAE by Apparent volume of distribution (Vz/F)
Measured: 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)
Measured: 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)
Measured: 365 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2023
- Study start14 Dec 2022
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hereditary AngioedemaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Phase 1, Single-Center, Randomized, Placebo-Controlled, Double Blind Single Ascending Dose Study in HV with expansion into HAE
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 53 participants (estimated)
Sponsor and investigators
- Lead sponsor
- ADARx Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Avance Clinical Pty Ltd.
- Responsible party
- Sponsor
- Investigators
- Lauge Farnaes, MD, Study director, ADARx Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05691361
- Sponsor's protocol ID
- ADX-324-101
- Status last verified
- Jun 2026
- First submitted
- 16 Dec 2022
- Last updated
- 16 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05691361
- Acronym / sponsor ID
- ADX-324-101
- Conditions
- Hereditary Angioedema
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 53 participants (estimated)
- Lead sponsor
- ADARx Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Avance Clinical Pty Ltd.
- Study start
- 14 Dec 2022 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 20 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
- Model description
- Phase 1, Single-Center, Randomized, Placebo-Controlled, Double Blind Single Ascending Dose Study in HV with expansion into HAE
| Arm | Type | Receives |
|---|---|---|
| PART A - Active ADX-324 administered to HV | Experimental | Drug: ADX-324For 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. |
| PART A- Placebo administered to HV | Placebo comparator | Drug: PlaceboFor 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. |
| PART B - ADX-324 administered to HAE participants | Experimental | Drug: ADX-324This 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. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (29 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ADX-324Also: siRNAsiRNA duplex oligonucleotide | Drug | PART A - Active ADX-324 administered to HV, PART B - ADX-324 administered to HAE participants |
| PlaceboAlso: Salinesaline | Drug | PART A- Placebo administered to HV |
Primary outcome
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
Safety in Healthy Volunteers
Time frame: 365 days
To evaluate the safety and tolerability of ADX-324 in HVs by change in baseline electrocardiogram (ECG) parameters (PR, QRS, QT, and QTcF intervals)
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
20 secondary outcomes
Pharmacokinetics in Healthy Volunteers
Time frame: 8 days
Pharmacokinetics in Healthy Volunteers
Time frame: 8 days
Pharmacokinetics in Healthy Volunteers
Time frame: 8 days
Pharmacokinetics in Healthy Volunteers
Time frame: 8 days
Pharmacokinetics in Healthy Volunteers
Time frame: 8 days
Pharmacokinetics in Healthy Volunteers
Time frame: 8 days
Pharmacokinetics in Healthy Volunteers
Time frame: 8 days
Pharmacokinetics in Healthy Volunteers
Time frame: 8 days
Pharmacodynamics in Healthy Volunteers
Time frame: 365 days
Pharmacodynamics in Healthy Volunteers
Time frame: 365 days
Pharmacokinetics in Hereditary Angioedema
Time frame: 365 days
Pharmacokinetics in Hereditary Angioedema
Time frame: 8 days
Pharmacokinetics in Hereditary Angioedema
Time frame: 8 days
Pharmacokinetics in Hereditary Angioedema
Time frame: 8 days
Pharmacokinetics in Hereditary Angioedema
Time frame: 8 days
Pharmacokinetics in Hereditary Angioedema
Time frame: 8 days
Pharmacokinetics in Hereditary Angioedema
Time frame: 8 days
Pharmacokinetics in Hereditary Angioedema
Time frame: 8 days
Pharmacodynamics in Hereditary Angioedema
Time frame: 365 days
Pharmacodynamics in Hereditary Angioedema
Time frame: 365 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lauge Farnaes, MD study director
ADARx Pharmaceuticals
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ADX-324 in people with Hereditary Angioedema, run by ADARx Pharmaceuticals, Inc. at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 16 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety in Healthy Volunteers (time frame: 365 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jun 2026.