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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT06205628
Ethics application status
Date submitted
4/01/2024
Date registered
16/01/2024
Date last updated
12/11/2024

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 participants with hypertension - Part 1 includes up to 7 sequential dose cohorts (4 planned and 3 optional) to evaluate doses ranging from 100 to 800 mg (Table 3). In each cohort, 8 participants will be randomized in a 3:1 ratio to ADX-850 or placebo with the option to increase enrollment to 16 participants at the Sponsor's discretion and with SRC agreement.

At the start of each cohort, 2 sentinel participants (1 ADX-850 and 1 placebo) will be treated. The Medical Monitor and Investigator will review the available safety data from the first 48 hours after dosing to ensure safety before continuing enrollment in that cohort.

Placebo comparator: PART 1 - Placebo administered to participants with hypertension - Part 1 includes up to 7 sequential dose cohorts (4 planned and 3 optional) to evaluate doses ranging from 100 to 800 mg (Table 3). In each cohort, 8 participants will be randomized in a 3:1 ratio to ADX-850 or placebo with the option to increase enrollment to 16 participants at the Sponsor's discretion and with SRC agreement.

At the start of each cohort, 2 sentinel participants (1 ADX-850 and 1 placebo) will be treated. The Medical Monitor and Investigator will review the available safety data from the first 48 hours after dosing to ensure safety before continuing enrollment in that cohort.

Experimental: PART 2 - Active ADX-850 administered to participants with hypertension - In Part 2, participants with hypertension will be dosed with ADX-850 in an open-label, parallel arm fashion. Participants whose SBP \>120 mmHg at Day 57 will be administered irbesartan, 150 to 300 mg, once daily. Dosing of the combination treatment group will begin with 2 sentinel participants who will be followed for safety for 48 hours after starting their irbesartan regimen before the decision is made by the Investigator and Medical Monitor to continue with combination treatment for all other participants who meet the criteria for irbesartan administration.

Experimental: PART 2 - Active ADX-850 plus ARB therapy administered to participants with hypertension - In Part 2, participants with hypertension will be dosed with ADX-850 in an open-label, parallel arm fashion. Participants whose SBP \>120 mmHg at Day 57 will be administered irbesartan, 150 to 300 mg, once daily. Dosing of the combination treatment group will begin with 2 sentinel participants who will be followed for safety for 48 hours after starting their irbesartan regimen before the decision is made by the Investigator and Medical Monitor to continue with combination treatment for all other participants who meet the criteria for irbesartan administration.


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 Participants with Hypertension
Timepoint [1] 0 0
365 days
Primary outcome [2] 0 0
PART 2 - Safety in Participants with Hypertension
Timepoint [2] 0 0
365 days
Secondary outcome [1] 0 0
PART 1 - Pharmacokinetics in Participants with Hypertension
Timepoint [1] 0 0
8 days
Secondary outcome [2] 0 0
PART 1 - Biomarker activity in Participants with Hypertension
Timepoint [2] 0 0
365 days
Secondary outcome [3] 0 0
PART 2 - Biomarker Activity in Participants with Hypertension on a stable dose of ARB
Timepoint [3] 0 0
365 days

Eligibility
Key inclusion criteria
* Body mass index (BMI) between 18 and 35 kg/m2
* Documentation of mild to moderate hypertension, mean of >130 and <165mmHg
* 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)
* Negative urine drug and breath alcohol test
* Must be a non-smoker for the duration of the study
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
* Blood donation within 30 days prior to study drug administration
* 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
30/09/2026
Actual
Sample size
Target
120
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
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
Avance Clinical Pty Ltd.
Address [2] 0 0
Country [2] 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/study/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
[email protected]
Contact person for scientific queries



Summary Results

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