Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620000536965
Ethics application status
Approved
Date submitted
14/12/2019
Date registered
1/05/2020
Date last updated
1/05/2020
Date data sharing statement initially provided
1/05/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
Evaluation of the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of PLN-74809
Scientific title
A Continued Evaluation of the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of PLN-74809 in Healthy Participants
Secondary ID [1] 299523 0
PLN-74809-104
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Idiopathic pulmonary fibrosis 314774 0
Primary Sclerosing Cholangitis 315782 0
Condition category
Condition code
Respiratory 313106 313106 0 0
Other respiratory disorders / diseases
Oral and Gastrointestinal 314067 314067 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 314068 314068 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) Phase trial. Participants will be randomised to either orally receive with PLN-74809 or placebo.

Active treatment will be PLN-74809

Experimental SAD dosing: PLN-74809 or placebo dosed orally, administered once daily for a single dose planned in 4 cohorts of 10 healthy participants per cohort for SAD, assessing a starting dose of 120mg and and increasing the dose for up to three (3x) additional cohorts. The specific dose to be administered to each additional cohort will be determined by the review of the previous cohorts safety and PK data by the study’s Safety Review Committee.

Experimental MAD dosing: PLN-74809 or placebo dosed orally, administered once daily for seven days planned in 4 cohorts of 10 healthy participants per cohort for MAD, assessing a starting dose of 60mg and and increasing the dose for up to three (3x) additional cohorts. The specific dose to be administered to each additional cohort will be determined by the review of the previous cohorts safety and PK data by the study’s Safety Review Committee.

Protocol excludes subjects who have participated in any other investigational drug trial within 30 days or 5 half-lives (whichever is long) of dosing in present study. Therefore while it is not specifically excluded and it may be possible, it is not the sponsor’s preference to have a subject who participated in the SAD to rescreen/enroll into the MAD dosing cohort.

Intervention is administered directly by staff at Phase 1 unit. Laboratory tests will also be monitored to assess adherence retrospectively.

Intervention code [1] 315779 0
Treatment: Drugs
Comparator / control treatment
Active: PLN-74809

Matching Placebo: Oral Solution, prepared to resemble the active treatment at each dose level
Control group
Placebo

Outcomes
Primary outcome [1] 321645 0
To assess the safety and tolerability of PLN-74809 for SAD subjects.
Timepoint [1] 321645 0
For SAD: Safety and tolerability assessments will be collected for 14 days following the first dose of PLN-74809 or placebo.

Safety and tolerability of PLN-74809 for SAD assessed by physical examination, vital signs, ECG & telemetry testing, laboratory testing.
Primary outcome [2] 322464 0
To assess the safety and tolerability of PLN-74809 for MAD subjects.
Timepoint [2] 322464 0
For MAD: Safety and tolerability assessments will be collected for 18 days following the first dose of PLN-74809 or placebo.

Safety and tolerability of PLN-74809 for MAD assessed by physical examination, vital signs, ECG & telemetry testing, laboratory testing.
Secondary outcome [1] 375741 0
To assess the single-dose pharmacokinetics (PK) of PLN-74809 in the SAD participants..

Single-dose pharmacokinetics (PK) of PLN-74809 assessed using plasma samples.

Parameters to be examined include: AUC, Cmax, tmax, t 1/2, ke, CL/F, VzF, R cmax, R auc.
Timepoint [1] 375741 0
For the SAD a total of 18 post-dose PK samples will be collected over each of the 7-day confinement period.
Secondary outcome [2] 375742 0
To assess renal clearance at steady state.

Assessment to be performed via urine PK for MAD.
Timepoint [2] 375742 0
Samples will be collected at Day 7 in the MAD

MAD cohorts will also include a 24 hour urine collection for PK on Day 7.
Secondary outcome [3] 378624 0
To assess the steady-state pharmacokinetics (PK) of PLN-74809 in the MAD participants.

Multiple-dose pharmacokinetics (PK) of PLN-74809 assessed using plasma samples.

Parameters to be examined include: AUC, Cmax, tmax, t 1/2, ke, CL/F, VzF, R cmax, R auc.
Timepoint [3] 378624 0
For the MAD at total of 36 post dose PK samples, both Peak and Trough, will be collected over the 14-day confinement period.

MAD cohorts will also include a 24 hour urine collection for PK on Day 7.

Eligibility
Key inclusion criteria

1. 18 to 55 years
2. Good general health, with no significant medical history and no clinically significant abnormalities at screening and/or before administration of the initial dose of study drug.
3. Body weight greater than or equal to 50 kg
4. Body mass index (BMI) between 18 and 30 kg/m2, inclusive.
5. Participants must use adequate contraception measures for males and female participants of childbearing potential
6. Understand the study procedures and agrees to participate in the study by giving written informed consent.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- History of clinically significant abnormalities or diseases.
- Pregnant or lactating females.
- Positive test for hepatitis C antibody (HCVAb), hepatitis B surface antigen (HBsAg), or human immunodeficiency virus (HIV) antibody at screening.
- Positive toxicology screening panel.
- History of substance abuse or dependency or history of recreational drug use.
- Alcohol consumption greater than 14 drinks per week for males (7 for females).
- Smokers or ‘vapers’ (cigarette or other modalities).
- Unable to refrain from or anticipates the use of any medications, including prescription and non-prescription drugs and herbal supplements.
- Unlikely to comply with the study protocol or, in the opinion of the Investigator, would not be a suitable candidate for participation in the study.
- Have participated in any other investigational drug trial within 30 days or 5 half-lives.

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)
Computer generated randomisation schedules will be prepared by a statistician prior to the start of the study. Subjects within a given dose level cohort will be randomised to receive PLN-74809 or Placebo in a ratio of 4 to 1 respectively.

Subjects will then be allocated a corresponding pre-prepared dosing vehicle labelled with the same randomisation number. Dosing vehicles containing active and placebo will be indistinguishable apart from the randomisation number on the label
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomization scheme and codes will be generated by an unblinded Statistician and provided to the site prior to study commencement.
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
Intervention assignment
Other
Other design features
Assignment is ascending dose escalation by cohort
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
The sample size has been set according to the prior SAD/MAD study design.

Safety data from all participants who received at least 1 dose of study drug will be incorporated into the final safety analysis.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
16/12/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
80
Accrual to date
60
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 14947 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 28232 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 304016 0
Commercial sector/Industry
Name [1] 304016 0
Pliant Therapeutics, Inc.
Country [1] 304016 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Pliant Therapeutics, Inc.
Address
260 Littlefield Avenue,
South San Francisco,
CA 94080, USA
Country
United States of America
Secondary sponsor category [1] 304190 0
Commercial sector/Industry
Name [1] 304190 0
InClin Pty Ltd
Address [1] 304190 0
210 / 25 Berry Street
North Sydney, NSW
Australia, 2060
Country [1] 304190 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304508 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 304508 0
Ethics committee country [1] 304508 0
Australia
Date submitted for ethics approval [1] 304508 0
21/10/2019
Approval date [1] 304508 0
21/11/2019
Ethics approval number [1] 304508 0
641/19

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

Contacts
Principal investigator
Name 97194 0
Dr Ingrid Hopper
Address 97194 0
The Nucleus Network Burnet Tower AMREP Precinct 89 Commercial Rd Melbourne VIC 3001
Country 97194 0
Australia
Phone 97194 0
+61 3 9076 8960
Fax 97194 0
Email 97194 0
[email protected]
Contact person for public queries
Name 97195 0
Taylor Kilfoil
Address 97195 0
InClin Pty. Ltd.
210 / 25 Berry Street
North Sydney, NSW
Australia, 2060
Country 97195 0
Australia
Phone 97195 0
+61 408 880 403
Fax 97195 0
Email 97195 0
[email protected]
Contact person for scientific queries
Name 97196 0
Erica Park
Address 97196 0
Pliant Therapeutics, Inc
260 Littlefield Avenue,
South San Francisco,
CA 94080, USA
Country 97196 0
United States of America
Phone 97196 0
+1 415 215 7768
Fax 97196 0
Email 97196 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
Data to remain confidential


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.