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Trial registered on ANZCTR


Registration number
ACTRN12624001334594p
Ethics application status
Submitted, not yet approved
Date submitted
17/10/2024
Date registered
4/11/2024
Date last updated
4/11/2024
Date data sharing statement initially provided
4/11/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Phase 1 Study to Investigate SIR4156 in Healthy Adult and Elderly Participants
Scientific title
A Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose Phase 1 Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of SIR4156, a novel NAMPT activator, in healthy adult and elderly participants.
Secondary ID [1] 312992 0
Sironax Australia Study SIR4156-AU-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Muscle degenerative diseases 335174 0
Condition category
Condition code
Musculoskeletal 331665 331665 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
SIR4156-AU-101 is a two-part study containing parts 1 and 2 with Part 2 also containing 3 parts - Part 2A, 2B and 2C. Each study part and stage will involve unique participants.

Part 1: Single ascending dose cohorts.
Part 1 evaluates the single-dose administration of SIR4156 capsules or matched placebo (a capsule that looks the same as the study drug but has no active substances): 3 mg, 10 mg, 30 mg 100 mg, 300 mg, 600 mg, and 1000 mg respectively. Each cohort will consist of 8 participants who will each receive a single dose of investigational drug or matched placebo under fasted state (after an overnight fast). Healthy volunteers will stay in the clinical research unit for the entire duration of dosing and will take the study drug under direct supervision of the clinical research unit staff.

Part 1 Cohort 4: Participants in Cohort 4 who complete the assigned fasted SAD capsule dosing will continue to remain in the clinical research unit to receive two additional assigned study intervention. The second fasted dosing of SIR4156 tablet or matched placebo (a tablet that looks the same as the study drug but has no active substances) will occur after a washout period of at least 5 days from their first dose and under fasted state. The third dosing of SIR4156 tablet or matched placebo will occur after a washout period of 4-7 days from their second dose and upon consumption of a high-fat breakfast. The High-Fat breakfast will be as per the FDA Guidance, e.g. two eggs fried in butter, two strips of bacon, two slices of toast with butter, four ounces of hash brown potatoes and eight ounces of whole milk). Participants will receive the same assigned study intervention as a part of the Food Effect and Relative Bioavailability study, Healthy volunteers will stay in the clinical research unit for the entire duration of dosing and will take study drug under the direct supervision of the clinical research unit staff.
Each of the SAD cohorts (except Cohort 4) will be observed for 11 days since the Day 1 dosing. Cohort 4 will be observed for 21 days since the Day 1 dosing. Safety, tolerability, and available PK data will be reviewed by the Safety Review Committee (SRC) for dose escalation and the actual dose to be administered may be adjusted accordingly.

Part 2: Multiple ascending dose cohorts
Part 2 of the study consists of three parts.
Part 2A: Multiple ascending dose cohorts in Healthy Volunteers
First three cohorts will consist of 13 participants each and Cohort 4 will consist of 10 participants who will each receive SIR4156 tablets or matched placebo: 30 mg, 100 mg, 200 mg and 400 mg respectively given by oral administration twice daily for 28 days (except Day 28, where only 1 morning dose will be given). Healthy volunteers will stay in the clinical research unit for the entire duration of dosing and will take study drug under direct supervision of the clinical research unit staff.
In Part 2A, after an observation and follow-up period of 38 days (from the first day of dosing) and review of the safety, tolerability, and available PK data of all participants enrolled in the previous cohorts, the next actual dose cohort may be adjusted by the SRC. These dose adjustments may involve either an increase or decrease in the planned dose or a change in the dosing frequency or a change in the fasting conditions (either fasted or fed). However the maximum dose will not exceed 400 mg BID and the maximum frequency of dosing will not exceed twice daily dosing.

Part 2B: Elderly Cohort
Part 2B consists of one cohort of 13 healthy elderly participants will each receive SIR4156 tablets or matched placebo; 200 mg given by oral administration twice daily for 28 days (except Day 28, where only 1 morning dose will be given). Healthy volunteers will stay in the clinical research unit for the entire duration of dosing and will take study drug under direct supervision of the clinical research unit staff. Part 2B will commence after the same dose level is reviewed by the SRC in Part 2A, however the planned 200 mg dose for Part 2C may be adjusted based on the outcome of SRC review of Part 2A. . In Part 2B, participants will be observed and followed for safety for 38 days (from the first day of dosing).

Part 2C: China Cohort
Part 2C of the study will be conducted in China. One cohort of 14 participants will receive SIR4156 or matched placebo; 400 mg given by oral administration twice daily for 28 days (except Day 28, where only 1 morning dose will be given). Healthy volunteers will stay in the clinical research unit for the entire duration of dosing and will take study drug under direct supervision of the clinical research unit staff. After an observation and follow-up period of 38 days (from the first day of dosing) participants will return to the clinical research unit for an End of Study Visit. Completion of this follow-up visit by the last participant in Part 2C will mark the end of the active study.
Part 2C will commence after the same dose level is reviewed by the SRC in Part 2A, however the planned 400 mg dose for Part 2C may be adjusted based on the outcome of SRC review of Part 2A.

In all study parts adherence to the intervention will be done via supervised drug administration.
Intervention code [1] 329525 0
Treatment: Drugs
Comparator / control treatment
Matching placebo: The placebo capsules contain microcrystalline cellulose.
Matching placebo: The tablets have the exact same composition as the active drug product minus the active ingredient.
Control group
Placebo

Outcomes
Primary outcome [1] 339392 0
Part 1: Integrated safety evaluation assessed as a composite primary outcome
Timepoint [1] 339392 0
Part 1: Single Ascending Dose (expect Cohort 4): Day-1 (the day before dosing) to Day 11 (10 days post-dose)
Clinical laboratory tests (haematology, chemistry, coagulation and urinalysis) will be assessed at Screening, and on Day-1, Day 1 (day of dosing), Day 2 (1 day post-dose), Day 3 (2 days post-dose), Day 4 (3 days post-dose) and Day 11 (10 days post-dose). Clinical laboratory tests (faecal occult blood test) will be performed at screening and Day-1 or at least one from the two; and on Day 2.
A complete physical examination will be assessed at Screening, and on Day -1 and Day 4.
Vital signs will be assessed at Screening, and on Day -1, Day 1, Day 2, Day 3, Day 4 and Day 11.
12-lead ECG will be assessed at Screening, and on Day 1, Day 2, Day 3, Day 4 and Day 11.
AEs/SAEs will be assessed at all timepoints, daily from Day-1 until Day 11.

Part 1: Food Effect and Relative Bioavailability cohort (Cohort 4): Day-1 (the day before dosing) to Day 21-24 (10-13 days post last dose)
Clinical laboratory tests (haematology, chemistry, coagulation and urinalysis) will be assessed at Screening, and on Day-1, Day 1 (day of first dose), Day 2 (1 day post first dose), Day 3 (2 days post first dose), Day 4 (3 days post first dose), Day 6 (day of second dose), Day 7 (1 day post second dose), Day 8 (2 days post second dose), Day 9 (3 days post second dose), Day 11 (+3 days window) (day of third dose), Day 12 (1 day post third dose), Day 13 (2 days post third dose), Day 14 (3 days post third dose) and Day 21 (+3 days window). Clinical laboratory tests (faecal occult blood test) will be performed at screening and Day-1 or at least one from the two; and on Day 2, Day 7 and Day 12.
A complete physical examination will be assessed at Screening, and on Day -1 and Day 14 (+3 days window).
Vital signs will be assessed at Screening, and on Day -1, Day 1, Day 2, Day 3, Day 4, Day 6, Day 7, Day 8, Day 9, Day 11, Day 12, Day 13, Day 14, and Day 21.
12-lead ECG will be assessed at Screening, and Day 1, Day 2, Day 3, Day 4, Day 6, Day 7, Day 8, Day 9, Day 11, Day 12, Day 13, Day 14, and Day 21.
AEs/SAEs will be assessed at all timepoints, daily from Day-1 until Day 21.



Primary outcome [2] 339741 0
Part 2: Integrated safety evaluation assessed as a composite primary outcome
Timepoint [2] 339741 0
Part 2A, 2B: Multiple Ascending Dose Cohorts: Day-2 (2 days before dosing) to Day 38 (7 days post last dose)
Clinical laboratory tests (haematology, chemistry, coagulation and urinalysis) will be assessed at Screening, and on Day-2 (2 days before dosing, Day 1 (1st day of dosing), Day 2 (2nd day of dosing), Day 5 (5th day of dosing), Day 8 (8th day of dosing), Day 11 (11th day of dosing), Day 14 (14th day of dosing), Day 17 (17th day of dosing), Day 20 (20th day of dosing), Day 23 (23rd day of dosing), Day 26 (26th day of dosing), Day 28 (28th day of dosing), Day 31 (31st day of dosing) and on Day 38. Clinical laboratory tests (faecal occult blood test) will be performed at screening and Day-2 or at least one from the two; and on Day 8, Day 14, Day 20 and Day 28.
A complete physical examination will be assessed at Screening, and on Day -2 and on Day 31.
Vital signs will be assessed at Screening, and on Day -2, Day -1, Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14, Day 15, Day 16, Day 17, Day 18, Day 19, Day 20, Day 21, Day 22, Day 23, Day 24, Day 25, Day 26, Day 27, Day 28, Day 29, Day 30, Day 31 and on Day 38.
12-lead ECG will be assessed at Screening, and Day 1, Day 2, Day 5, Day 8, Day 11, Day 14, Day 17, Day 20, Day 23, Day 26, Day 28, Day 31 and on Day 38.
AEs/SAEs will be assessed at all timepoints, daily from Day -2 until Day 38.

Part 2C: Multiple Ascending Dose Cohorts: Day-1 (1 day before dosing) to Day 38 (7 days post last dose)
Clinical laboratory tests (haematology, chemistry, coagulation and urinalysis) will be assessed at Screening, and on Day-1, Day 1 (1st day of dosing), Day 2 (2nd day of dosing), Day 5 (5th day of dosing), Day 8 (8th day of dosing), Day 11 (11th day of dosing), Day 14 (14th day of dosing), Day 17 (17th day of dosing), Day 20 (20th day of dosing), Day 23 (23rd day of dosing), Day 26 (26th day of dosing), Day 28 (28th day of dosing), Day 31 (31st day of dosing) and on Day 38. Clinical laboratory tests (faecal occult blood test) will be performed at screening and Day-1 or at least one from the two; and on Day 8, Day 14, Day 20 and Day 28.
A complete physical examination will be assessed at Screening, and on Day-1 and on Day 31.
Vital signs will be assessed at Screening, and on Day -1, Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14, Day 15, Day 16, Day 17, Day 18, Day 19, Day 20, Day 21, Day 22, Day 23, Day 24, Day 25, Day 26, Day 27, Day 28, Day 29, Day 30, Day 31 and on Day 38.
12-lead ECG will be assessed at Screening, and Day 1, Day 2, Day 5, Day 8, Day 11, Day 14, Day 17, Day 20, Day 23, Day 26, Day 28, Day 31 and on Day 38.
AEs/SAEs will be assessed at all timepoints, daily from Day-1 until Day 38.
Secondary outcome [1] 439748 0
Pharmacokinetic profile Part 1 (SAD)
Timepoint [1] 439748 0
Blood samples collected at pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 60 and 72 hours post each dose.
Secondary outcome [2] 439749 0
Pharmacokinetic profile Part 2A, 2B and 2C (MAD)
Timepoint [2] 439749 0
Blood samples collected on Day 1 pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours post Day 1 morning dose. On Days 2, 5, 8, 11, 14, 17, 20, 23 and Day 26 blood plasma samples will be collected prior to and 1 hour after the morning dose on each day. On Day 28-31 pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 60 and 72 hours post Day 28 morning dose.

Eligibility
Key inclusion criteria
• Must be capable of giving a signed informed consent
• Participants in good health based on medical history, physical examinations, vital signs, 12-lead ECGs, clinical laboratory tests as determined by the Investigator.
• Body Mass Index (BMI) within the range 18 to 32 kg/m2 (inclusive) except for Part 2C China Cohort to be 19 to 24 kg/m2 inclusive, and body weight not less than 50 kg.
• Adhere to effective double barrier contraception or are proven post-menopausal

For elderly participants, in addition:
• Male or female elderly participants aged 60 to 75 years old (inclusive) who are considered healthy or have managed, stable disease in the opinion of the Investigator.
• Elderly participant has any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease that is not well managed and stable, as judged by the PI or designee.

For China cohort, in addition:
• Body mass index (BMI) of 19 to 24 kg/m2 inclusive, and body weight not less than 50 kg.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
• Any clinical significant abnormalities in laboratory test results deemed clinically significant by the Investigator.
• History of bleeding disorders from gastrointestinal or other sites.
• Positive pregnancy test at Screening or Day -1
• Active or prior hepatitis B infection or positive test for SIV or Hepatitis C
• Any clinically significant cardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease. Note: elderly cohort can have stable, well managed disease.

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)
Simple randomization using a randomization table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

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
27/11/2024
Actual
Date of last participant enrolment
Anticipated
1/06/2025
Actual
Date of last data collection
Anticipated
10/07/2025
Actual
Sample size
Target
132
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 27109 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 43183 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 317430 0
Commercial sector/Industry
Name [1] 317430 0
Sironax Aus Pty Ltd
Country [1] 317430 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Sironax Aus Pty Ltd
Address
Country
Australia
Secondary sponsor category [1] 319718 0
None
Name [1] 319718 0
Address [1] 319718 0
Country [1] 319718 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 316151 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 316151 0
Ethics committee country [1] 316151 0
Australia
Date submitted for ethics approval [1] 316151 0
02/10/2024
Approval date [1] 316151 0
Ethics approval number [1] 316151 0

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

Contacts
Principal investigator
Name 136946 0
Dr Sam Francis
Address 136946 0
Nucleus Network Pty Ltd Level 5, Burnet Tower, 89 Commercial Rd, Melbourne 3004, Victoria
Country 136946 0
Australia
Phone 136946 0
+61 3 8593 9801
Fax 136946 0
Email 136946 0
s.francis@nucleusnetwork.com.au
Contact person for public queries
Name 136947 0
Dr Sam Francis
Address 136947 0
Nucleus Network Pty Ltd Level 5, Burnet Tower, 89 Commercial Rd, Melbourne 3004, Victoria
Country 136947 0
Australia
Phone 136947 0
+61 1800 243 733
Fax 136947 0
Email 136947 0
melbourne@nucleusnetwork.com.au
Contact person for scientific queries
Name 136948 0
Dr Sam Francis
Address 136948 0
Nucleus Network Pty Ltd Level 5, Burnet Tower, 89 Commercial Rd, Melbourne 3004, Victoria
Country 136948 0
Australia
Phone 136948 0
+61 1800 243 733
Fax 136948 0
Email 136948 0
melbourne@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
No individual data will be released in any form


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.