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Trial registered on ANZCTR


Registration number
ACTRN12624000632594p
Ethics application status
Submitted, not yet approved
Date submitted
21/04/2024
Date registered
16/05/2024
Date last updated
16/05/2024
Date data sharing statement initially provided
16/05/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Single and multiple ascending dose study of oral ZKN-0013 or placebo given randomly to healthy volunteers to evaluate the safety, tolerability and the amount of drug in the body after drug administration.
Scientific title
A Combined Single and Multiple Ascending Dose (SAD-MAD) Phase 1, Randomized, Double-Blinded, Placebo-Controlled, Multiple Dose Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Oral ZKN-0013 in Healthy Subjects
Secondary ID [1] 312011 0
None
Universal Trial Number (UTN)
EL-013
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Dermatology 333620 0
Condition category
Condition code
Skin 330307 330307 0 0
Dermatological conditions
Human Genetics and Inherited Disorders 330308 330308 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
ZKN-0013 is a modified macrolide
SAD cohorts:
• Cohort 1: ZKN-0013 15 mg or placebo orally once
• Cohort 2: ZKN-0013 50 mg or placebo orally once
• Cohorts 3 up to 7: dose levels to be determined based on Human PK modeling after SAD Cohorts 1 and 2

MAD cohorts
• Up to 7 cohorts: ZKN-0013 or placebo orally once daily for 15 days. Dose levels to be determined based on Human PK modeling after SAD Cohorts 1 and 2

Both ZKN-0013 and placebo will be administered as oral capsules.

Subjects will be randomized to receive single and then multiple doses of ZKN-0013 or placebo at a ratio of 3:1 in each cohort: Six subjects will receive ZKN-0013 and two will receive placebo.

Study drug administration will be recorded in each subject file to ensure compliance.
Intervention code [1] 328463 0
Treatment: Drugs
Comparator / control treatment
Placebo, oral capsules filled with pharmaceutical grade microcrystalline cellulose (MCC).
Control group
Placebo

Outcomes
Primary outcome [1] 338051 0
To assess the safety and tolerability of single ascending oral dose of ZKN-0013.
Timepoint [1] 338051 0
First subject in (FSI) to last subject out (LSO)
SAD participants: from signing consent at screening visit to admission to the unit on Day -1 and to Day s release and on Days 3, 4, 5, 8 and 14.
Primary outcome [2] 338052 0
To study the pharmacokinetics (PK) of ZKN-0013 administered as single oral dose.
Pharmacokinetic parameters of ZKN-0013 including Cmax, tmax, Clast, Tlast, AUCt, AUC24h, AUC48h, AUC72h, AUC96h, AUC168h, AUCinf, AUClast, t1/2, Vd/F, and CL/F, accumulation ratio (Rac) of all samples collected at pre-dose and post-dose
Timepoint [2] 338052 0
Plasma PK will be collected from first dose on Day 1 to last visit on Day 14
Day 1: before dosing, 5, 15, 30 minutes, 1, 3, 6, 12, 16, 18, 24 hours post dose, and on 48 hr (Day 3), 72 hr (Day 4), 96 hr (Day 5), 168 hr (Day 8) and Day 14
Urine PK will be collected before dosing, in a window of 0-6hr, 6-12hr, 12-18hr, 18-24 hr and spot checks on Day4 and Day 5.
Skin biopsy will be collected in selected cohort beyond cohort 3.
Primary outcome [3] 338146 0
Safety and tolerability of multiple ascending oral doses of ZKN-0013.
Timepoint [3] 338146 0
First subject in (FSI) to last subject out (LSO)
MAD participants: from signing consent at screening visit, admission to the unit on Day -1 and to Day 16 release and on Days 18, 19, 22 and 29.
Secondary outcome [1] 434683 0
This is an additional primary outcome
To study the pharmacokinetics (PK) of ZKN-0013 administered as multiple oral doses.
Timepoint [1] 434683 0
Plasma PK will be collected from first dose on Day 1 to last visit on Day 29
Day 1: before dosing, 5, 15, 30 minutes, 1, 3, 6, 12, 16, 18, 24 hours post dose, and on Days 3-16 as well as on Days 18, 19, 22 and 29.
Urine PK will be collected before dosing, in a window of 0-6hr, 6-12hr, 12-18hr, 18-24 hr and on Days 8, 15, 18, 19 and 29.

Skin biopsy will be collected in selected cohorts

Eligibility
Key inclusion criteria
- Healthy females and males ages 18-55 inclusive
- Contraception requirement for woman of child bearing potential and males with female partners of child bearing potential
- Not using prescription medication 14 days prior to admission; and 7 days prior to admission for over-the-counter (OTC) medications/vitamins/supplements (Exceptions contraception, Acetaminophen equal to 2g/day, stand dose of vitamins)
- Non-smoking and no use of any tobacco or nicotine products (by declaration) for a period of at least 1 months prior to screening visit
- Be on no medication with potential to impair hepatic and renal function at the time of screening
- Normal hepatic enzymes and bilirubin
- Normal renal function (glomerular filtration rate greater than 60 mL/min/1.73m2)
- Negative human immunodeficiency virus (HIV) or Hepatitis B surface antigen (HBsAg) or Hepatitis C (HCV) Ab by serology
- No history of alcohol or other drugs of abuse
- Body Mass Index (BMI) of 18.0 to 32.0 kg/m2 (inclusive)
- No vaccines given within 14 days of dosing
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Dosed in another clinical trial within at least 10 tissue half-lives prior to dosing
- Evidence or history of clinically relevant hepatic, hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease
- History of regular alcohol consumption exceeding 14 drinks/week for females or 21 drinks/week for males within 6 months of screening
- Screening supine BP equal to 140 mm Hg (systolic) or equal to 90 mm Hg (diastolic)
- Screening supine (for 5 minutes) 12-lead electrocardiogram (ECG) demonstrating QTc greater than 450 millisecond for men and greater than 470 millisecond for women, or a QRS interval >120 millisecond
- Subjects with any abnormalities in clinical laboratory tests at screening, considered by the study physician as clinically significant
- Pregnant or breastfeeding female subjects
- Subjects who donated blood or received blood or plasma derivatives in 30 days preceding study drug administration
- Subjects with any acute medical situation (e.g., acute infection) within 48 hours (h) of - Screening or start of dosing
- Major surgery within last 3 months, or minor surgery in the last 1 month, or any planned surgery during the trial.
- Any other condition or prior therapy that in the opinion of the study physician or designee would make the participant unsuitable for this study

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)
Allocation involved contacting the holder of the allocation schedule who was "off-site"
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table from a statistic book
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
28/06/2024
Actual
Date of last participant enrolment
Anticipated
15/03/2025
Actual
Date of last data collection
Anticipated
13/04/2025
Actual
Sample size
Target
128
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 316360 0
Commercial sector/Industry
Name [1] 316360 0
Eloxx Pharmaceuticals (AUS) Pty Ltd
Country [1] 316360 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Eloxx Pharmaceuticals (AUS) Pty Ltd
Address
Country
Australia
Secondary sponsor category [1] 318545 0
None
Name [1] 318545 0
Address [1] 318545 0
Country [1] 318545 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 315166 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 315166 0
https://www.alfredhealth.org.au/research/ethics-research-governance
Ethics committee country [1] 315166 0
Australia
Date submitted for ethics approval [1] 315166 0
08/05/2024
Approval date [1] 315166 0
Ethics approval number [1] 315166 0

Summary
Brief summary
Eloxx Pharmaceuticals has developed a new product which works on mutated gene and allows for production of the correct protein instead of the defective protein typical to a number of hereditary diseases. The product is called ZKN-0013 and it is taken orally. The purpose of this research is to determine whether ZKN-0013 is safe and well tolerated in humans. In addition, the study purpose is to learn about the study drug properties. The participants will take one or multiple doses of ZKN-0013 during their participation based on the group they will be assigned to.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 133878 0
Dr Philip Ryan
Address 133878 0
Nucleus Network Melbourne. Level 5, Burnet Tower, 89 Commercial Rd, Melbourne, Victoria, 3004
Country 133878 0
Australia
Phone 133878 0
+61385939801
Fax 133878 0
Email 133878 0
p.ryan@nucleusnetwork.com.au
Contact person for public queries
Name 133879 0
Dr. Philip Ryan
Address 133879 0
Nucleus Network Melbourne. Level 5, Burnet Tower, 89 Commercial Rd, Melbourne, Victoria, 3004
Country 133879 0
Australia
Phone 133879 0
+1800 243 733
Fax 133879 0
Email 133879 0
melbourne@nucleusnetwork.com
Contact person for scientific queries
Name 133880 0
Dr. Philip Ryan
Address 133880 0
Nucleus Network Melbourne. Level 5, Burnet Tower, 89 Commercial Rd, Melbourne, Victoria, 3004
Country 133880 0
Australia
Phone 133880 0
+61385939801
Fax 133880 0
Email 133880 0
p.ryan@nucleusnetwork.com.au

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


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.