Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001534774
Ethics application status
Approved
Date submitted
25/11/2022
Date registered
12/12/2022
Date last updated
4/09/2023
Date data sharing statement initially provided
12/12/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
First in human clinical study of a novel drug PTC607 to assess its safety and tolerability in healthy volunteers
Scientific title
Phase 1 dose-escalation study assessing the safety and pharmacokinetics of PTC607 in healthy volunteers
Secondary ID [1] 308481 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Huntington's Disease 328293 0
Condition category
Condition code
Neurological 325341 325341 0 0
Neurodegenerative diseases
Human Genetics and Inherited Disorders 325451 325451 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Part 1 is a single ascending dose part of the study in healthy volunteers. It will consist with up to 5 sequential cohorts of 8 participants each. In each cohort, participants will be randomised to receive a single dose of either PTC607 or placebo in a 3:1 ratio (6 participants will receive PTC607 and 2 will receive placebo) in a fasted state and in a double-blinded fashion. PTC607 and placebo will be administered as a suspension orally. In each cohort, sentinel dosing will be performed in 2 participants (1 participant with PTC607 and 1 participant with placebo). The remaining 6 participants (5 of whom will be randomised to PTC607 and 1 of whom to placebo) will be dosed after at least 24 hours, if no clinically significant safety issues are observed in sentinels. The starting dose will be 5 mg of PTC607. The maximum dose escalation between cohorts will be no more than 3-fold to a maximum of 120 mg. The Safety Review Committee will meet to determine the dose-level for the next cohort based on PK and safety results from the previous cohorts.
Healthy volunteers will stay in the clinical research unit for 3 nights and will take study drug after at least 10 hours fasting under direct supervision of the clinical research unit staff. Monitoring the adherence to the intervention may include mouth checks.
Intervention code [1] 324924 0
Treatment: Drugs
Comparator / control treatment
Microcrystalline cellulose will be used as placebo in doses corresponding to PTC607.
Control group
Placebo

Outcomes
Primary outcome [1] 333203 0
Safety and tolerability of single ascending doses of PTC607 in healthy participants through review of:
- vital signs (blood pressure and heart rate assessed by sphygmomanometer, body temperature by thermometer)
- electrocardiogram parameters via 12-lead ECGs
- Holter monitoring (in addition to ECGs in Cohorts 1..3, 1.4 and 1.5 only).
- clinical safety laboratory tests: serum chemistry (including liver function tests, electrolytes, glucose, kidney function tests, cholesterol and triglycerides), full blood count and coagulation tests will be assessed using whole blood samples, urinalysis will be assessed using urine samples
- treatment-emergent adverse events
Timepoint [1] 333203 0
Vital signs: Screening (Day -28 to -2), admission (Day -1), Days 1, 2 and 3.
12 lead ECG: single ECGs at screening (Day -28 to -2), admission (Day -1), pre-dose on Day 1 and before discharge on Day 3. Triplicate ECGs 4 (+/-1) hours post-dosing on Day 1.
Holter monitoring: continuously for 24 hours from pre-dose on Day 1.
Clinical laboratory tests: Screening (Day -28 to -2), admission (Day -1) and discharge (Day 3).
Adverse events: continuously from admission (Day -1) until Day 3 (discharge from the CRU) and on Day 30 (+/- 7 days)
Secondary outcome [1] 416144 0
Pharmacokinetics of single doses of PTC607 in healthy participants through assessment of plasma concentration-time curves, maximum observed plasma concentration, time to maximum plasma concentration, and terminal half-life.
Timepoint [1] 416144 0
Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2) and 48 hours post-dose (Day 3)
Secondary outcome [2] 416731 0
Exploratory pharmacodynamic parameter huntingtin (HTT) pre-RNA splicing measured in the blood of healthy participants.
Timepoint [2] 416731 0
Pre-dose, 2, 3, 4, 6, 8 and 12 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2) and 48 hours post-dose (Day 3).

Eligibility
Key inclusion criteria
1. 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 30.0 kg/m2 with a body weight of greater than or equal to 50.0 kg for male
participants and a body weight of greater than or equal to 45.0 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.
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 greater than or equal to 21 units per week for male
participants and greater than or equal to 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 <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 involved 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 statistic 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 study drug.
Safety set: This analysis set includes participants who received the study drug. The safety set will be employed in the analysis of tolerability and safety variables.
PK set: This analysis set comprises all participants included in the safety set who did not
violate the protocol in a way that might affect the evaluation of the effect of the study drug(s) on the PK parameters, ie, without major protocol violations or deviations. The PK set will be employed in the analysis of PK variables. Participants dosed with placebo will not be
included in the PK set.
PD set: This analysis set includes participants from the safety set who had at least 1 PD
assessment post-baseline. The PD set will be employed in the analysis of the exploratory
variables.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
15/01/2023
Actual
16/01/2023
Date of last participant enrolment
Anticipated
17/05/2023
Actual
21/07/2023
Date of last data collection
Anticipated
14/07/2023
Actual
21/08/2023
Sample size
Target
40
Accrual to date
Final
40
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 23638 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 39058 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 312726 0
Commercial sector/Industry
Name [1] 312726 0
PTC Therapeutics, Inc.
Country [1] 312726 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
CTI Clinical Trial and Consulting Services Australia Pty Ltd.
Address
Level 21, 207 Kent Street,
Sydney NSW 2000
Country
Australia
Secondary sponsor category [1] 314345 0
None
Name [1] 314345 0
Address [1] 314345 0
Country [1] 314345 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312023 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 312023 0
Ethics committee country [1] 312023 0
Australia
Date submitted for ethics approval [1] 312023 0
19/10/2022
Approval date [1] 312023 0
24/11/2022
Ethics approval number [1] 312023 0

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

Contacts
Principal investigator
Name 123210 0
Prof Sepehr Shakib
Address 123210 0
CMAX Clinical Research,
Level 5, 21 North Terrace,
Adelaide SA 5000
Country 123210 0
Australia
Phone 123210 0
+61 411100278
Fax 123210 0
Email 123210 0
[email protected]
Contact person for public queries
Name 123211 0
Sepehr Shakib
Address 123211 0
CMAX Clinical Research,
Level 5, 21 North Terrace,
Adelaide SA 5000
Country 123211 0
Australia
Phone 123211 0
+61 411100278
Fax 123211 0
Email 123211 0
[email protected]
Contact person for scientific queries
Name 123212 0
Amy-Lee Bredlau
Address 123212 0
PTC Therapeutics, Inc.
100 Corporate Court
South Plainfield, NJ 07080
Country 123212 0
United States of America
Phone 123212 0
+1 914 707 2785
Fax 123212 0
Email 123212 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

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

Documents added automatically
No additional documents have been identified.