Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT06205628




Registration number
NCT06205628
Ethics application status
Date submitted
4/01/2024
Date registered
16/01/2024
Date last updated
24/04/2024

Titles & IDs
Public title
Safety, Tolerability, PK and PD of ADX-850 in Participants With Hypertension
Scientific title
A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ADX-850 in Participants With Hypertension
Secondary ID [1] 0 0
ADX-850-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypertension 0 0
Hypertension,Essential 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Hypertension
Cardiovascular 0 0 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ADX-850
Treatment: Drugs - Placebo
Treatment: Drugs - Angiotensin Receptor Blockers

Experimental: PART 1 - Active ADX-850 administered to patients with hypertension - For Cohort 1 in Part 1 (SAD), 8 participants will be randomized in a 3:1 ratio; 6 participants to active (ADX-850) : 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.
For Cohort 2, the option either to enroll 8 or expand to 16 patients in a 3:1 ratio will be made following review of Cohort 1. For Cohorts 3 and 4, 16 patients will be randomized in a 3:1 ratio; 12 patients to active (ADX-850) : 4 patients to control (matched placebo).

Placebo Comparator: PART 1 - Placebo administered to patients with hypertension - For Cohort 1 in Part 1 (SAD), 8 participants will be randomized in a 3:1 ratio; 6 participants to active (ADX-850) : 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.
For Cohort 2, the option either to enroll 8 or expand to 16 patients in a 3:1 ratio will be made following review of Cohort 1. For Cohorts 3 and 4, 16 patients will be randomized in a 3:1 ratio; 12 patients to active (ADX-850) : 4 patients to control (matched placebo).

Experimental: PART 2 - Active ADX-850 administered to patients with hypertension - This will be initiated at the dose level determined by the Safety Review Committee from SAD in Part 1. The treatment of hypertension patients is an open-label study.

Experimental: PART 2 - Active ADX-850 plus ARB therapy administered to patients with hypertension - Following ADX-850 dosing in Part 2, patients with remaining elevated blood pressure will additionally receive regular dosing of an angiotensin receptor blocker as an as-indicated concomitant therapy.


Treatment: Drugs: ADX-850
siRNA duplex oligonucleotide

Treatment: Drugs: Placebo
Saline

Treatment: Drugs: Angiotensin Receptor Blockers
Angiotensin receptor blocker
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
PART 1 - Safety in Patients with Hypertension
Timepoint [1] 0 0
365 days
Primary outcome [2] 0 0
PART 2 - Safety in Patients with Hypertension
Timepoint [2] 0 0
365 days
Secondary outcome [1] 0 0
PART 1 - Plasma Pharmacokinetics in Patients with Hypertension
Timepoint [1] 0 0
8 days
Secondary outcome [2] 0 0
PART 1 - Plasma Pharmacokinetics in Patients with Hypertension
Timepoint [2] 0 0
8 days
Secondary outcome [3] 0 0
PART 1 - Plasma Pharmacokinetics in Patients with Hypertension
Timepoint [3] 0 0
8 days
Secondary outcome [4] 0 0
PART 1 - Plasma Pharmacokinetics in Patients with Hypertension
Timepoint [4] 0 0
8 days
Secondary outcome [5] 0 0
PART 1 - Plasma Pharmacokinetics in Patients with Hypertension
Timepoint [5] 0 0
8 days
Secondary outcome [6] 0 0
PART 1 - Plasma Pharmacokinetics in Patients with Hypertension
Timepoint [6] 0 0
8 days
Secondary outcome [7] 0 0
PART 1 - Biomarker Activity in Patients with Hypertension
Timepoint [7] 0 0
365 days
Secondary outcome [8] 0 0
PART 2 - Biomarker Activity in Patients with Hypertension
Timepoint [8] 0 0
365 days

Eligibility
Key inclusion criteria
- Body mass index (BMI) between 18 and 35 kg/m2

- Body weight =55 kg

- No use of antihypertensive medication for a minimum of 2 weeks or 5 half-lives

- Access to and ability to use antihypertensive medication/access to emergency services
to treat hyper- or hypotensive events

- 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

- Willing to start or switch to irbesartan as concomitant ARB therapy, if applicable
(Part 2 only)
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Any significant medical history

- Secondary hypertension

- Active malignancy and/or history of malignancy in the past 5 years

- History of liver disease, Gilbert's syndrome, nonalcoholic steatohepatitis, severe
steatosis, or abnormal liver function test

- Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, red
blood cell (RBC), hemoglobin, hematocrit, reticulocytes, gamma-glutamyl transferase
(GGT), and creatinine must be within normal range at screening and prior to dosing

- Any active infection or acute illness

- Major surgery or significant traumatic injury occurring within 3 months

- 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

- Mean sitting diastolic BP (DBP) =110 mmHg at any time prior to randomization.

- Orthostatic hypotension

- eGFR <60 mL/min/1.73m2

- Abnormal potassium levels <3.5 and >5 mmol/L

- History or presence of clinically significant ECG abnormalities and corrected QTcF
>450 ms prior to dosing

- Positive serology tests (HepB, Hep C, HIV)

- Use of unapproved prescription, vaccines, supplements/vitamins, or over-the counter
medication

- Treatment with another investigational product concurrently or within 30 days prior to
the first study drug administration

- Known hypersensitivity to any of the study drug ingredients

- Pregnancy, intent to become pregnant during the course of the study, or lactating
women

- History or presence of alcohol abuse

- Night shift workers (regular working hours between 10:00 PM and 6:00 AM)

- Known history of intolerance to ARB medication (Part 2 only)

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
21/03/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/06/2026
Actual
Sample size
Target
72
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,WA
Recruitment hospital [1] 0 0
CMAX Clinical Research - Adelaide
Recruitment hospital [2] 0 0
Linear Clinical Research - Nedlands
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
6009 - Nedlands

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
ADARx Pharmaceuticals, Inc.
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
ADARx Australia Pty Ltd
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The first-in-human Phase 1 study will evaluate the safety, tolerability, pharmacokinetics
(PK), and pharmacodynamics (PD) of ADX-850 in patients with hypertension.
Trial website
https://clinicaltrials.gov/ct2/show/NCT06205628
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Markus P Schlaich, MD
Address 0 0
Country 0 0
Phone 0 0
+61892240382
Fax 0 0
Email 0 0
markus.schlaich@uwa.edu.au
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT06205628