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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05691361




Registration number
NCT05691361
Ethics application status
Date submitted
16/12/2022
Date registered
20/01/2023

Titles & IDs
Public title
Safety, Tolerability, PK, PD of ADX-324 in Healthy Volunteers and Hereditary Angioedema Patients
Scientific title
A Phase 1, Randomized, Placebo-Controlled, Double Blind Single Ascending Dose Study in Healthy Volunteers and an Expansion Cohort in Patients With Hereditary Angioedema to Evaluate the Safety, Tolerability, PK and PD of ADX-324
Secondary ID [1] 0 0
ADX-324-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hereditary Angioedema 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Blood 0 0 0 0
Other blood disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ADX-324
Treatment: Drugs - Placebo

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.

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.

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.


Treatment: Drugs: ADX-324
siRNA duplex oligonucleotide

Treatment: Drugs: Placebo
saline
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety in Healthy Volunteers
Timepoint [1] 0 0
365 days
Primary outcome [2] 0 0
Safety in Healthy Volunteers
Timepoint [2] 0 0
365 days
Primary outcome [3] 0 0
Safety in Hereditary Angioedema
Timepoint [3] 0 0
365 days
Secondary outcome [1] 0 0
Pharmacokinetics in Healthy Volunteers
Timepoint [1] 0 0
8 days
Secondary outcome [2] 0 0
Pharmacokinetics in Healthy Volunteers
Timepoint [2] 0 0
8 days
Secondary outcome [3] 0 0
Pharmacokinetics in Healthy Volunteers
Timepoint [3] 0 0
8 days
Secondary outcome [4] 0 0
Pharmacokinetics in Healthy Volunteers
Timepoint [4] 0 0
8 days
Secondary outcome [5] 0 0
Pharmacokinetics in Healthy Volunteers
Timepoint [5] 0 0
8 days
Secondary outcome [6] 0 0
Pharmacokinetics in Healthy Volunteers
Timepoint [6] 0 0
8 days
Secondary outcome [7] 0 0
Pharmacokinetics in Healthy Volunteers
Timepoint [7] 0 0
8 days
Secondary outcome [8] 0 0
Pharmacokinetics in Healthy Volunteers
Timepoint [8] 0 0
8 days
Secondary outcome [9] 0 0
Pharmacodynamics in Healthy Volunteers
Timepoint [9] 0 0
365 days
Secondary outcome [10] 0 0
Pharmacodynamics in Healthy Volunteers
Timepoint [10] 0 0
365 days
Secondary outcome [11] 0 0
Pharmacokinetics in Hereditary Angioedema
Timepoint [11] 0 0
365 days
Secondary outcome [12] 0 0
Pharmacokinetics in Hereditary Angioedema
Timepoint [12] 0 0
8 days
Secondary outcome [13] 0 0
Pharmacokinetics in Hereditary Angioedema
Timepoint [13] 0 0
8 days
Secondary outcome [14] 0 0
Pharmacokinetics in Hereditary Angioedema
Timepoint [14] 0 0
8 days
Secondary outcome [15] 0 0
Pharmacokinetics in Hereditary Angioedema
Timepoint [15] 0 0
8 days
Secondary outcome [16] 0 0
Pharmacokinetics in Hereditary Angioedema
Timepoint [16] 0 0
8 days
Secondary outcome [17] 0 0
Pharmacokinetics in Hereditary Angioedema
Timepoint [17] 0 0
8 days
Secondary outcome [18] 0 0
Pharmacokinetics in Hereditary Angioedema
Timepoint [18] 0 0
8 days
Secondary outcome [19] 0 0
Pharmacodynamics in Hereditary Angioedema
Timepoint [19] 0 0
365 days
Secondary outcome [20] 0 0
Pharmacodynamics in Hereditary Angioedema
Timepoint [20] 0 0
365 days

Eligibility
Key inclusion criteria
Part A - HV



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
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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



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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
14/12/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
26/12/2025
Actual
Sample size
Target
53
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
CMAX Clinical Research - Adelaide
Recruitment postcode(s) [1] 0 0
5000 - Adelaide

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
ADARx Pharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Nicholas Farinola, MD
Address 0 0
CMAX Clinical Research Pty Ltd
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
CMAX Reception
Address 0 0
Country 0 0
Phone 0 0
+610870887900
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05691361