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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05876312




Registration number
NCT05876312
Ethics application status
Date submitted
17/05/2023
Date registered
25/05/2023
Date last updated
15/11/2024

Titles & IDs
Public title
Safety, Tolerability, PK and PD of ADX-038 in Healthy Participants and Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients
Scientific title
A Phase 1, Randomized, Double Blind, Placebo-Controlled, Single Ascending Dose Study in Healthy Participants Followed by a Phase 2a Open Label Study in Participants with PNH and Residual Anemia to Evaluate the Safety, Tolerability, PK and PD of ADX-038
Secondary ID [1] 0 0
ADX-038-101
Universal Trial Number (UTN)
Trial acronym
PNH
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Paroxysmal Nocturnal Hemoglobinuria (PNH) 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ADX-038
Treatment: Drugs - Placebo

Experimental: Phase 1 - Active ADX-038 administered to HP - For each cohort in Phase 1 (SAD), 8 participants will be randomized in a 3:1 ratio; 6 participants to active (ADX-038): 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: Phase 1- Placebo administered to HP - For each cohort in Phase 1 (SAD), 8 participants will be randomized in a 3:1 ratio; 6 participants to active (ADX-038): 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: Phase 2a - ADX-038 administered to PNH participants - This will be initiated at the dose level determined by the Safety Review Committee from SAD in HPs. The treatment of PNH participants is an open-label study.


Treatment: Drugs: ADX-038
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 Paroxysmal Nocturnal Hemoglobinuria Participants
Timepoint [2] 0 0
365 days
Secondary outcome [1] 0 0
Pharmacokinetics in Healthy Participants
Timepoint [1] 0 0
8 days
Secondary outcome [2] 0 0
Pharmacodynamics in Healthy Participants
Timepoint [2] 0 0
365 days
Secondary outcome [3] 0 0
Pharmacodynamics in Paraxysmal Nocturnal Hemoglobinuria
Timepoint [3] 0 0
365 days
Secondary outcome [4] 0 0
Pharmacodynamics in Paraxysmal Nocturnal Hemoglobinuria
Timepoint [4] 0 0
365 days
Secondary outcome [5] 0 0
Pharmacodynamics in Healthy Participants
Timepoint [5] 0 0
365 days

Eligibility
Key inclusion criteria
Phase 1 Key Inclusion Criteria

* 18 to 55 years of age
* Participants who are healthy as determined by medical evaluation
* History of recent meningococcal, pneumococcal and Haemophilus influenzae type B vaccinations or willing to be vaccinated
* Screening tests negative for illicit drug, nicotine, and alcohol use

Phase 1 Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion Criteria

* History of any significant medical conditions, except for completely excised non-melanoma skin cancer or low grade cervical intraepithelial neoplasia without evidence of recurrence within the prior 3 months
* Any viral, bacterial, parasitic, or fungal infection within the prior 30 days
* Frequent respiratory, nasopharyngeal or ear infections (more than 5 infections per year)
* History of environmental exposure or sick contact that increase the risk of meningococcal, pneumococcal and/or Haemophilus influenza type B infections
* Complement deficiency or immunodeficiency syndrome
* Major surgery or significant traumatic injury within the prior 3 months
* History of anaphylaxis or hypersensitivity reactions
* History of penicillin allergy
* History of splenectomy
* History of alcohol abuse or illicit drug use
* Donated plasma within the prior 7 days
* Donated blood or loss more than 400 milliliters of blood (excluding blood volume drawn at screening) within the prior 90 days
* Screening estimated creatinine clearance of less than 60 milliliters per minute
* Screening hematology, serum chemistry, or coagulation parameters that are outside the normal range
* Screening vital signs that are abnormal per protocol specification
* Screening electrocardiogram findings that are clinically significant
* Pregnant or lactating females
* Use of prescription (except for contraceptives and study-related prophylactic antibiotics) or over-the counter medications (except for paracetamol or ibuprofen) or vitamins/supplements within the prior 7 days
* Use of medications that may reduce the effectiveness of hormonal contraceptives within the prior 28 days
* Use of an investigational therapeutics within the prior 30 days or within the expected washout (at least 5 half-lives)
* Unwilling or unable to adhere to study-related prophylactic antibiotics requirements

Phase 2a Key Inclusion Criteria

* at least 18 years of age
* Diagnosis of paroxysmal nocturnal hemoglobinuria based on documented clone size
* Hemoglobin concentration of less than 12 gram per deciliter
* History of recent meningococcal, pneumococcal and Haemophilus influenzae type b vaccinations or willing to be vaccinated
* On a stable anti-C5 regimen for greater than or equal to 12 weeks prior to Day 1

Phase 2a Key Exclusion Criteria

* Any viral, bacterial, parasitic, or fungal infection within the prior 14 days
* HIV, active hepatitis C or hepatitis B infection
* History of meningococcal or tuberculosis infection
* History of malignancy in the past 5 years, except for completely excised non-melanoma skin cancer or low grade cervical intraepithelial neoplasia with no evidence of recurrence within the prior 3 months
* Complement deficiency syndrome
* History of hematopoietic stem cell transplantation
* History of splenectomy
* Inflammatory bowel disease, systemic lupus erythematosus, rheumatoid arthritis, or chronic liver disease
* Clinically significant and uncontrolled medical conditions including, but not limited to, thromboembolic disease, acute coronary syndrome, and diabetes
* Pregnant or lactating females
* Use of an investigational therapeutics within the prior 30 days or within the expected washout period (at lest 5 half-lives)
* Abstain from alcohol consumption for 48 hrs before day of dosing and restrict to no more than an average of 14 standard drinks per week

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 analysing the results/data
Intervention assignment
Parallel
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
7/08/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/09/2026
Actual
Sample size
Target
50
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Nucleus Network Brisbane - Brisbane
Recruitment hospital [2] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [3] 0 0
Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
4006 - Brisbane
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment postcode(s) [3] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United Kingdom
State/province [1] 0 0
London

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
Novotech (Australia) Pty Limited
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The first-in-human Phase 1/Phase 2a study described herein will evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of ADX-038 in both healthy participants (HP) and in patients with paroxysmal nocturnal hemoglobinuria (PNH).
Trial website
https://clinicaltrials.gov/study/NCT05876312
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
Richard Friend, MD
Address 0 0
Country 0 0
Phone 0 0
+61 403 415 925
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/NCT05876312