Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623001325695
Ethics application status
Approved
Date submitted
22/11/2023
Date registered
18/12/2023
Date last updated
18/12/2023
Date data sharing statement initially provided
18/12/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
First in human study of multiple doses of a novel drug PTC607 to assess its safety and tolerability in healthy participants
Scientific title
Phase 1 dose-escalation study assessing the safety and pharmacokinetics of multiple doses of PTC607 in healthy volunteers
Secondary ID [1] 310977 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record
ACTRN12623000300673 and ACTRN12622001534774 are sub-studies of this study

Health condition
Health condition(s) or problem(s) studied:
Huntington's Disease 332062 0
Condition category
Condition code
Neurological 328789 328789 0 0
Neurodegenerative diseases
Human Genetics and Inherited Disorders 328790 328790 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a multiple ascending dose study in healthy volunteers. It will consist of up to 3 sequential cohorts of 8 participants each. In each cohort, participants will be randomised to receive multiple doses of either PTC607 or placebo in tablet formulation in a 3:1 ration (6 participants will receive PTC607 and 2 will receive placebo) with food for 14 days. The following dose regimens have been selected:
- Cohort 3.1: 15 mg PTC607 or matching placebo once daily for 14 consecutive days
- Cohort 3.2: 30 mg PTC607 or matching placebo once daily for 14 consecutive days
- Cohort 3.3: depending on pharmacokinetics data from cohorts 3.1 and 3.2, either 30 mg or 60 mg PTC607/placebo every other day for 14 days (7 doses in total).
The Safety Review Committee will meet to review the results of each cohort prior to proceeding to the following cohort in this study.
Healthy participants will stay in the clinical research unit for 18 consecutive nights and will take study drug with food between 8:00 am and 11:00 am under direct supervision of the clinical research unit staff. The study drug and matching placebo will be taken with 240 mL of water.
Monitoring the adherence to the intervention may include mouth checks.
Intervention code [1] 327408 0
Treatment: Drugs
Comparator / control treatment
Matching placebo tablets will be be used in doses corresponding to PTC607 tablets consisting of microcrystalline cellulose, lactose anhydrous, croscarmellose sodium, magnesium stearate, poloxamer 407, colloidal silicon dioxide as an orange film coated tablet.
Control group
Placebo

Outcomes
Primary outcome [1] 336597 0
Safety and tolerability of multiple-ascending doses of PTC607 administered for 14 days in healthy participants through review of:
- vital signs
- electrocardiogram parameters
- clinical safety laboratory test results:
- suicidal ideation and suicidal behaviour
- treatment-emergent adverse events (TEAE)
- treatment-emergent adverse events leading to premature discontinuation of study drug
Timepoint [1] 336597 0
Vital signs: Screening (once between Day -28 to Day -2 before commencement of PTC607), admission (once on Day -1 before commencement of PTC607), once pre-dose every day on Days 1 to 14 post-commencement of PTC607, once on discharge day (Day 18 post-commencement of PTC607 for cohorts 3.1 and 3.2 or Day 17 post-commencement of PTC607 for cohort 3.3)
Electrocardiogram parameters:
- 12 lead ECG: Screening (single measurement between Day -28 to -2 before commencement of PTC607), single measurement on admission (Day -1 before commencement of PTC607); triplicate measurements at 60 min, 45 min and 30 min pre-dose and 0.5 hr, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr and 24 hr post-dose on Day 1 and Day 14 (Cohorts 3.1 and 3.2)/Day 13 (Cohort 3.3) post commencement of PTC607.
- Holter monitoring: continuously for 24 hours from pre-dose on Day 1 and Day 14 (Cohorts 3.1 and 3.2)/Day 13 (Cohort 3.3)
Secondary outcome [1] 429006 0
Pharmacokinetics (PK) of PTC607 following multiple doses in healthy participants
Timepoint [1] 429006 0
For Cohort 3.1 and Cohort 3.2, PK samples will be collected on Day 1 of commencement of PTC607 at pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12 hours post-dose and 24 hours (prior to dose on Day 2).
On Day 2 through Day 13 post commencement of PTC607 at pre-dose (within 30 minutes) and 4 hours post-dose. The 24h sample following first dose could serve as the pre-dose sample for Day 2. On last day of dosing (Day 14 post commencement of PTC607) at pre-dose (within 30 minutes) and 0.5, 1, 2, 3, 4, 6, 8, 12 hours post-dose; 24 and 36 hours (Day 15 post commencement of PTC607); 48 and 60 hours (Day 16 post commencement of PTC607); 72 hours (Day 17 post commencement of PTC607); and 96 hours (Day 18 post commencement of PTC607).
For Cohort 3.3, PK samples will be collected on Day 1 of commencement of PTC607 at pre-dose and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post-dose; 24 and 36 hours (Day 2 post commencement of PTC607); and 48 hours (Day 3 post commencement of PTC607, prior to
the second dose). On Day 3 through Day 12 post commencement of PTC607, at approximately the same time of dose administration (prior dose if no dose treatment on the day) or at pre-dose (within 30 minutes) and 4 hours (only if dose is to be administered on the day). On Day 13 post commencement of PTC607 (the seventh dose administration) at pre-dose (within 30 minutes) and at 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post-dose; 24 and 36 hours (Day 14 post commencement of PTC607); 48 and 60 hours (Day 15 post commencement of PTC607); 72 hours (Day 16 post commencement of PTC607); and 96 hours (Day 17 post commencement of PTC607).
Secondary outcome [2] 429008 0
Effect of PTC607 administered for 14 days on huntingtin (HTT) pre-mRNA splicing level in the blood of healthy participants.
Timepoint [2] 429008 0
One sample will be collected anytime after check in on Day -1 before commencement of PTC607 for all cohorts.
For Cohort 3.1 and Cohort 3.2, mRNA samples will be collected on Day 1 of commencing PTC607 pre-dose at -60 and -30 minutes and 0.5, 1, 2, 3, 4, 6, 8, 12 hours post-dose and 24 hours (prior to dose on Day 2 post commencement of PTC607). On Day 2 through Day 13 post commencement of PTC607 at pre-dose (within 30 minutes) and 4 hours post-dose. The 24h sample following first dose could serve as the pre-dose sample for Day 2 post commencement of PTC607. On last day of dosing (Day 14 post commencement of PTC607) at pre-dose (within 30 minutes) and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post-dose; 24 and 36 hours (Day 15 post commencement of PTC607), 48 and 60 hours (Day 16 post commencement of PTC607); 72 hours (Day 17 post commencement of PTC607); and 96 hours (Day 18 post commencement of PTC607).
For Cohort 3.3, mRNA samples will be collected on Day 1 of commencement of PTC607 pre-dose at -60 and -30 minutes and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post-dose; 24 and 36 hours (Day 2 post commencement of PTC607); and 48 hours (Day 3 post commencement of PTC607, prior to the second dose). On Day 3 through Day 12 post commencement of PTC607 at pre-dose and 4 hours (if dose is administered) or at approximately the same time of dose administration (if no dose treatment on the day). The 48h sample following first dose could serve as the pre-dose sample for Day 3 post commencement of PTC607. On Day 13 post commencement of PTC607 (the seventh dose administration) at pre-dose and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post-dose; 24 and 36 hours (Day 14 post commencement of PTC607); 48 and 60 hours (Day 15 post commencement of PTC607); 72 hours (Day 16 post commencement of PTC607); and 96 hours (Day 17 post commencement of PTC607).
Secondary outcome [3] 429683 0
Effect of PTC607 administered for 14 days on HTT protein level in the blood of healthy participants.
Timepoint [3] 429683 0
One sample will be collected anytime after check in on Day -1 prior to commencement of PTC607 immediately after collection of PK samples.
For Cohort 3.1 and 3.2, HTT samples will be collected on Day 1 of commencement of PTC607 at pre-dose and 12 hours post-dose. On Day2 through Day 13 post commencement of PTC607, pre-dose. On Day 14 post commencement of PTC607, HTT samples will be collected at pre-dose and 12, 24, 48, 72 and 96 hours post-dose.
For Cohort 3.3, HTT samples will be collected on Day 1 of commencement of PTC607 at pre-dose and 12 hours post-dose. ON Day 2 through Day 12 post commencement of PTC607 at pre-dose or approximately the same time of dose administration. On Day 13 post commencement of PTC607, HTT samples will be collected at pre-dose and 12, 24, 48, 72 and 96 hours post-dose.

Eligibility
Key inclusion criteria
1. Healthy males and females aged 18 to 65 years inclusive at Screening.
2. Participants able to provide informed consent.
3. Body mass index of greater than or equal to 18.5 and less than or equal to 30 kg/m2 with a body weight of greater than or equal to 50 kg for male participants and a body weight of greater than or equal to 45 kg for female participants at Screening.
4. Generally healthy as determined by the investigator based on medical evaluation, including medical history, physical examination, laboratory test results, ECG and vital signs.
5. Male participants must be willing to use 2 acceptable contraceptive methods for the duration of the study and for a minimum of 6 months after the last dose and female participants of childbearing potential must be willing to use 2 acceptable contraceptive
methods for the duration of the study and for a minimum of 30 days after the last dose. Postmenopausal female participants must have had greater than or equal to 12 months of spontaneous amenorrhea (with follicle-stimulating hormone of greater than or equal to 30 mIU/mL at Screening).
6. All female participants of childbearing potential must have a negative serum pregnancy
test result at Screening and a negative urine pregnancy test on Day -1.
7. Male participants must agree to not donate sperm for the duration of the study and for at
least 6 months after the last dose.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Participants that participated in any drug or device clinical investigation within 60 days
prior to Screening or who anticipate participating in any drug or device clinical investigation within the duration of this study.
2. Prior or ongoing medical condition (eg, concomitant illness, psychiatric condition), medical history, and/or physical findings that, in the investigator’s opinion, could adversely affect the safety of the participant or could impair the assessment of study results.
3. An abnormal general neurological examination.
4. Presence of any clinically significant abnormality during Screening.
5. Any psychological or emotional problems, any disorders, or resultant therapy that is likely to invalidate informed consent or limit the ability of the participant to comply with the protocol requirements.
6. A positive hepatitis B surface antigen, positive hepatitis C antibody, or HIV antibody result at Screening.
7. Donation of plasma within 7 days prior to dosing. Donation or loss of blood (excluding volume drawn at Screening or menses) of 50 to 499 mL within 30 days or more than 499 mL within 56 days prior to dosing.
8. Excessive alcohol consumption (regular alcohol intake equal to or greater than 21 units per week for male participants and equal to or greater than 14 units per week for female participants) within 6 months prior to Screening. One unit (8 g) is equivalent to a half pint (280 mL) of beer, 1 measure (25 mL) of spirits, or 1 small glass (125 mL) of wine.
9. The participant is a smoker or uses other nicotine-containing products. Ex-smokers must
have ceased smoking >3 months prior to Screening. Smokers who consume equal to or less than 4 tobacco products per week are allowed.
10. The participant has consumed grapefruit (or its juice), star fruit, pomegranate, pomelo,
tangelo, or Seville orange-containing products in the 1 week before Screening.
11. A positive urine drug screen, cotinine screen, or alcohol breath test at Screening or on
Day -1 of each treatment period.
12.Females who are pregnant or nursing.
13. Participant has previously received PTC607.

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 is concealed and involves contacting the holder of the allocation schedule (randomisation list), who is an off-site unblinded pharmacist.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table from a statistics book.
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
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
A formal statistical analysis plan will be developed and finalised before database lock.
Analysis populations:
All-treated set: includes all treated participants who received at least 1 dose of study drug.
Safety set: includes participants who received at least 1 dose of study drug. The safety set will be employed in the analysis of tolerability and safety variables.
PK Full Analysis set: this set is defined as all participants who received at least 1 dose of study drug and have at least 1 reported concentration.
PK Analysis set: this analysis set is defined as all participants in the PK full analysis set who have at least 1 measurable drug concentration without a major protocol deviation or any other events that may affect the evaluation of the effect of the study drug on the key PK parameters. The PK set will be employed in summary and/or analysis of PK concentration and parameters. Participants dosed with placebo will not be included in the PK set.
PD set: this analysis set is defined as all participants from the safety set who had at least 1 PD assessment post-baseline.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
2/01/2024
Actual
Date of last participant enrolment
Anticipated
1/04/2024
Actual
Date of last data collection
Anticipated
26/04/2024
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 25866 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 41699 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 315236 0
Commercial sector/Industry
Name [1] 315236 0
PTC Therapeutics, Inc.
Country [1] 315236 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
CTI Clinical Trial and Consulting Services Australia Pty Ltd
Address
Level 4, 478 George Street, Sydney NSW 2000
Country
Australia
Secondary sponsor category [1] 317283 0
None
Name [1] 317283 0
Address [1] 317283 0
Country [1] 317283 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314160 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 314160 0
Ethics committee country [1] 314160 0
Australia
Date submitted for ethics approval [1] 314160 0
20/11/2023
Approval date [1] 314160 0
29/11/2023
Ethics approval number [1] 314160 0

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

Contacts
Principal investigator
Name 130630 0
Prof Sepehr Shakib
Address 130630 0
CMAX Clinical Research, Level 5, 21 North Terrace, Adelaide SA 5000
Country 130630 0
Australia
Phone 130630 0
+61 411100278
Fax 130630 0
Email 130630 0
[email protected]
Contact person for public queries
Name 130631 0
Sepehr Shakib
Address 130631 0
CMAX Clinical Research, Level 5, 21 North Terrace, Adelaide SA 5000
Country 130631 0
Australia
Phone 130631 0
+61 411100278
Fax 130631 0
Email 130631 0
[email protected]
Contact person for scientific queries
Name 130632 0
Amy-Lee Bredlau
Address 130632 0
PTC Therapeutics, Inc. 100 Corporate Court, South Plainfield, NJ 07080
Country 130632 0
United States of America
Phone 130632 0
+1 914 707 2785
Fax 130632 0
Email 130632 0
[email protected]

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

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No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.