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Trial registered on ANZCTR


Registration number
ACTRN12620000264987
Ethics application status
Approved
Date submitted
6/02/2020
Date registered
28/02/2020
Date last updated
28/02/2020
Date data sharing statement initially provided
28/02/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A Healthy Volunteer Study Evaluating the Tolerability and Pharmacokinetics of PRN473 Topical
Scientific title
A Phase I, Randomized, Double-Blind, Placebo-Controlled, Ascending Single Dose Study with a Repeat-Dose Arm to Evaluate the Safety, Tolerability and Pharmacokinetics of Topically Administered PRN473 in Healthy Adult Participants
Secondary ID [1] 296917 0
PRN473-0002
Universal Trial Number (UTN)
U1111-1246-8518
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Immune-mediated dermatological diseases 315886 0
Condition category
Condition code
Inflammatory and Immune System 314163 314163 0 0
Autoimmune diseases
Skin 314553 314553 0 0
Dermatological conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study consists of 2 parts (Part A and Part B).

Part A consists of 3 cohorts, which will be evaluated sequentially. Participants in each cohort of Part A will receive a single ascending dose of either 0.5%, 2%, or 5% PRN473 Topical or placebo. They will stay overnight in the clinic until completion of the 24 hour post dose assessment and then be discharged. The participant will then return on Day 4 for end of study assessments.

Part B consists of 1 cohort in which the participants will receive repeat doses of either PRN473 topical (dose determined in Part A) or placebo. Each participant will be dosed twice a day for 7 days. They will remain at the clinic for the 7 days of dosing and discharge on the 9th day . The participant will then return on Day 10 for end of study assessments.

Each application of topical PRN473 will be 14 g that will contain either 0.5% , 2%, or 5% of PRN473 . Topical PRN473 will be applied over a patch of skin on the back measuring about 35 cm x 40 cm.
Intervention code [1] 316571 0
Treatment: Drugs
Comparator / control treatment
Placebo, a water-based topical formulation containing the same ingredients as the investigational medicinal product except that titanium dioxide is used in place of the active ingredient to match the appearance of the investigational medicinal product.
Control group
Placebo

Outcomes
Primary outcome [1] 322548 0
To assess the safety of single and repeat doses of PRN473 Topical when administered to healthy adults as assessed by the collection of safety data, such as adverse events, clinical laboratory tests, vital signs, ECGs, skin irritation assessments, and physical exams.

Safety data collected by adverse events can be gathered by participant self-reporting and clinical examination of skin. Possible adverse events include skin erythema, irritation, and allergic reaction”

Timepoint [1] 322548 0
Safety will be assessed throughout the study, starting from time of dose through to end of study visit.
Secondary outcome [1] 378905 0
To assess the plasma pharmacokinetics of single and repeat doses of PRN473 Topical in healthy adults as assessed by determining the pharmacokinetic parameters (Cmax, Tmax, AUC, half-life, elimination rate, clearance, and volume of distribution) via blood samples.
Timepoint [1] 378905 0
In Part A of the study, blood samples will be taken at pre-dose and 30 minutes, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose.

In Part B of the study, blood samples will be taken on Day 1 and Day 7 at pre-dose and 30 minutes, 1, 2, 3, 4, 6, 8, 10, and 12, hours post-dose. Additional samples will be taken on Day 3 and Day 5 at pre-dose only and at 24, 36, and 48 hours post Day 7 dose.
Secondary outcome [2] 378906 0
To assess the urine pharmacokinetics of repeat doses of PRN473 Topical in health adults as assessed by determining excretion, renal clearance, and systemic clearance via urine samples in Part B of the study.
Timepoint [2] 378906 0
Urine samples will be collected each day on Day 1 and Day 7, pre-dose and over 12 hours post the first dose.
Secondary outcome [3] 378907 0
To assess immunoglobulin levels as assessed by blood samples
Timepoint [3] 378907 0
Blood samples will be collected on Day 1 and Day 7 at pre-dose, 1 hour, 4 hour, and 12 hour post morning dose. Then on Day 3 and Day 5, a single blood samples will be collected pre-dose. Another sample will be collected on Day 8.
Secondary outcome [4] 380109 0
To a assess BTK occupancy of peripheral blood mononuclear cells as assessed by blood samples.
Timepoint [4] 380109 0
Blood samples will be collected on Day 1 and Day 7 at pre-dose, 1 hour, 4 hour, and 12 hour post morning dose. Then on Day 3 and Day 5, a single blood samples will be collected pre-dose. Another sample will be collected on Day 8.

Eligibility
Key inclusion criteria
1. Healthy adult men or women, who are surgically sterile or postmenopausal, 18 to 55 years old and able to provide written informed consent
2. Must have clinical laboratory values within normal.
3. If male, agree to use an effective means of contraception
4. Must have appropriate skin characteristics at the application site
Minimum age
18 Years
Maximum age
55 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Women who are pregnant or lactating
2. Positive testing for human immunodeficiency virus , hepatitis B surface antigen, or hepatitis C antibodies
3. Clinically significant medical history of chronic or acute disease or infection
4. History of alcoholism, drug abuse or significant tobacco use
5. Use of a a tanning salon 2 weeks prior to study start
6. Blood donation or significant blood loss of more than 400 milliliter within 60 days prior to Screening
7. Participation in another clinical trial of a drug or device whereby the last investigational drug or device administration is within 60 days prior to the first study drug administration or 5 half-lives, whichever is longer
8. Previous exposure to PRN473 oral formulation

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)
A statistician will prepare a Randomization Schedule and send a copy to the unblinded study pharmacist. The unblinded study pharmacist will then label the study drug in a blinded fashion in accordance with the Randomisation Schedule. The label will include the randomisation number but not the treatment. The Randomization Schedule will not be made available to clinic personnel.
Participants who complete the screening assessments and meet all of the eligibility criteria will be enrolled into the study and will be assigned a unique Randomisation Number.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computerised randomisation schedule will be created by a statistician who is not otherwise involved in the study.
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
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis
Descriptive statistics (for example, arithmetic mean, standard deviation, median, minimum and maximum) will be calculated for continuous valued measurements for each treatment group. Differences between baseline and each applicable scheduled post-baseline time point will similarly be summarized by treatment group where appropriate. Frequency summaries will be applied for categorical data for each treatment group, and for each scheduled time point. Additional summaries or analyses may be applied to the data as appropriate.

No formal hypothesis testing will be performed for this study.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 15636 0
Linear Clinical Research - Nedlands
Recruitment postcode(s) [1] 29045 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 301488 0
Commercial sector/Industry
Name [1] 301488 0
Principia Biopharma Inc.
Address [1] 301488 0
220 East Grand Avenue
South San Francisco, CA 94080
Country [1] 301488 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Principia Biopharma Inc.
Address
220 East Grand Avenue
South San Francisco, CA 94080
Country
United States of America
Secondary sponsor category [1] 301182 0
Commercial sector/Industry
Name [1] 301182 0
Clinical Network Services
Address [1] 301182 0
Level 2, 381 MacArthur Avenue
Hamilton, QLD 4006
Country [1] 301182 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302232 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 302232 0
129 Glen Osmond Road Eastwood Adelaide
South Australia 5063
Ethics committee country [1] 302232 0
Australia
Date submitted for ethics approval [1] 302232 0
15/01/2020
Approval date [1] 302232 0
18/02/2020
Ethics approval number [1] 302232 0
2020-01-025

Summary
Brief summary
The purpose of this research study is to assess the safety and tolerability of PRN473 Topical as well as the pharmacokinetics (PK - how your body absorbs medications). We are doing this study in healthy men and women to find out:
• Does the drug have any side-effects and is it well tolerated when given topically as a single dose and in multiple doses?
• How much of the drug when given topically gets into the blood stream, and how long does the body take to get rid of it?
This study will compare PRN473 Topical with placebo. A placebo has no active drug in it. One group of participants will receive PRN473 Topical and another group will receive the topical placebo. The effects seen in participants receiving the study drug will be compared to the effects seen in participants who receive the placebo.

This study will look at how participants react to, and how the human body uses PRN473 Topical at different dose levels. In total there are planned to be 2 parts to the study. Part A will look at the effects of a single topical dose of the study drug and Part B will look at the effects of multiple topical doses of the study drug
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 89526 0
Dr Ana Sun
Address 89526 0
Linear Clinical Research
L1, B Block
1 HospitalAvenue
Nedlands, WA 6009
Country 89526 0
Australia
Phone 89526 0
+61 8 63825100
Fax 89526 0
Email 89526 0
asun@linear.org.au
Contact person for public queries
Name 89527 0
Dr Marianne Kavanagh
Address 89527 0
Principia Biopharma Inc.
220 East Grand Avenue
South San Francisco,CA 94080
Country 89527 0
United States of America
Phone 89527 0
+1 650 416 7775
Fax 89527 0
Email 89527 0
marianne.kavanagh@principiabio.com
Contact person for scientific queries
Name 89528 0
Dr Wendy Yeh
Address 89528 0
Principia Biopharma Inc.
220 East Grand Avenue
South San Francisco,CA 94080
Country 89528 0
United States of America
Phone 89528 0
+1 650 402 2119
Fax 89528 0
Email 89528 0
wendy.yeh@principiabio.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
IPD will not be available.
What supporting documents are/will be available?
No other documents available
Summary results
No Results