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Trial registered on ANZCTR


Registration number
ACTRN12620000693921
Ethics application status
Approved
Date submitted
5/05/2020
Date registered
22/06/2020
Date last updated
9/06/2021
Date data sharing statement initially provided
22/06/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
An interventional study to evaluate the effect and safety of PRN473 topical on skin reactions of otherwise healthy participants with allergies to common allergens.
Scientific title
A Phase I, Open-Label, Placebo-Controlled, Challenge Study to Evaluate the Pharmacologic Activity of Topically Administered PRN473 on the Skin Reaction Induced by Challenge Agents via a Skin Prick in Participants with Immunoglobulin E-Mediated Allergies
Secondary ID [1] 300718 0
PRN473-0003
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Immunoglobulin E-Mediated Allergies 316532 0
Condition category
Condition code
Inflammatory and Immune System 314778 314778 0 0
Allergies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Screening
The first skin prick test will be conducted at screening day. Allergen solutions containing one of the following: cat hair, dust mite and ryegrass will be applied to the forearm at Screening via a Skin Prick Test by a nurse and the response will be measured at 15 minutes. Individual participant responsiveness to the three allergens will be confirmed by comparing each allergen response to the positive (histamine) and negative (saline) controls.

Day 1
Eligible participants that respond to two allergens at screening will enroll and attend a Day 1 visit. The two allergens that elicit the greatest wheal response for each participant will be applied to the skin on the participants’ back via Skin Prick Test.

Treatment
The upper back of eligible participants will be divided into left and right zones. The left zone will be used for prophylactic purpose with treatments (placebo and PRN473 treatments) applied 2 hours prior to skin prick and the right zone will be used for therapeutic purpose (placebo and PRN473 treatments) applied 5 minutes after the skin prick.

Each zone will be divided into 6 microzones of approximately 14cm squared surface area as below.

Left Zone-Prophylaxis
Microzones-Two skin pricks per microzone
L-MZ#1 positive histamine control and negative saline control
L-MZ#2 Allergen #1 and Allergen #2 without treatment
L-MZ#3 Allergen #1 and Allergen #2 with placebo topical applied 2 hour prior to skin prick
L-MZ#4 Allergen #1 and Allergen #2 with PRN473 5 % topical applied 2 hour prior to skin prick
L-MZ#5 Allergen #1 and Allergen #2 with PRN473 2 % topical applied 2 hour prior to skin prick
L-MZ#6 Allergen #1 and Allergen #2 with PRN473 0.5 % topical applied 2 hour prior to skin prick

Right Zone-Therapeutic
Microzones-Two skin prick per microzone
R-MZ#1 positive histamine control and negative saline control
R-MZ #2 Allergen #1 and Allergen #2 without treatment
R-MZ #3 Allergen #1 and Allergen #2 with placebo topical applied 5 minutes after skin prick
R-MZ #4 Allergen #1 and Allergen #2 with PRN473 5 % topical applied 5 minutes after skin prick
R-MZ #5 Allergen #1 and Allergen #2 with PRN473 2 % topical applied 5 minutes after skin prick
R-MZ #6 Allergen #1 and Allergen #2 with PRN473 0.5 % topical applied 5 minutes after skin prick

On day 1, skin assessment after each test will be conducted up to 60 minutes and the same
allergens will be used on both prophylactic and therapeutic zones.

Dose
Placebo and three strengths of PRN473 topical (0.5%, 2%, and 5%) will be applied topically in parallel to the backs of each participant in designated microzones. For each strength, approximately 250 mg of topical product applied over 14 cm squared microzone area as
the starting amount in the first few subject. The amount applied may be increased up to 750mg per 14cm squared microzone area for future subjects, based on the ability of treatment to prevent skin reaction. The study team will analyze the observed wheal and erythema assessments on Day 1.

For each participant the amount of applied treatment will be predetermined before Day 1 application. The same amount of treatment will be applied for prophylactic (left) and therapeutic (right) zones. No dose adjustment will be made after application of treatments on Day 1.

All Skin Prick Tests, as well as PRN473 treatments and placebo will be administered by nurse. The responses to allergens are measured by a nurse for 60 minutes after Skin Prick Test and validated by another nurse.

Procedures, including dose application, skin prick test administration and outcome measures will be fully documented by site staff, and overseen by an observing study team member. An application grid (per site procedures) will be used to ensure treatments are applied within the applicable microzones. Routine quality review will occur to assess logistical compliance to protocol requirements.
Intervention code [1] 317037 0
Prevention
Intervention code [2] 317746 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] 323143 0
To evaluate the pharmacologic activity of a PRN473 topical formulation against Type I, IgE-mediated skin reactions when administered prophylactically.
The endpoint- The erythema size within each microzone will be assessed for Treatment 1 (Prophylaxis)
Timepoint [1] 323143 0
Skin assessments will be conducted 10, 15, 20, 30, 40 and 60 minutes after the SPT.
Primary outcome [2] 323880 0
To evaluate the pharmacologic activity of a PRN473 topical formulation against Type I, IgE-mediated skin reactions when administered therapeutically.
The endpoint: The erythema size within each microzone will be assessed for Treatment 2 (Therapeutic).
Timepoint [2] 323880 0
Skin assessments will be conducted 10, 15, 20, 30, 40 and 60 minutes after the SPT.
Primary outcome [3] 324179 0
To evaluate the pharmacologic activity of a PRN473 topical formulation against Type I, IgE-mediated skin reactions when administered prophylactically.
The endpoint -The wheal size within each microzone will be assessed for Treatment 1 (Prophylaxis)
Timepoint [3] 324179 0
Skin assessments will be conducted 10, 15, 20, 30, 40 and 60 minutes after the SPT.
Secondary outcome [1] 380950 0
To evaluate the safety and tolerability of a PRN473 topical formulation.
This will be assessed by looking at the following:
- Incidence and severity of adverse events;
- Incidence of serious adverse events and suspected unexpected serious adverse reactions;
- Clinically significant changes from pre-treatment on Day 1 in:
-- Laboratory evaluations (hematology, chemistry, urinalysis);
-- Vital signs;
- Physical examinations
Timepoint [1] 380950 0
Adverse events will be reported for all participants from the time of consent until the completion of the Day 4 Follow-up/EOS visit
Clinical laboratory evaluations of serum chemistry, hematology, and urinalysis will be performed at Screening, pre-dose on Day 1, and at Day 4 /EOS.
Vital signs, including blood pressure, pulse rate, respiratory rate, and body temperature will be measured at Screening, pre-dose on Day 1, and Day 4/EOS.
A full physical examination will be performed at Screening, with focused physical exams conducted when clinically indicated.
Secondary outcome [2] 383938 0
Primary Outcome:
To evaluate the pharmacologic activity of a PRN473 topical formulation against Type I, IgE-mediated skin reactions when administered therapeutically.
The endpoint: The wheal size within each microzone will be assessed for Treatment 2 (Therapeutic).
Timepoint [2] 383938 0
Primary Timepoint:
Skin assessments will be conducted 10, 15, 20, 30, 40 and 60 minutes after the SPT.

Eligibility
Key inclusion criteria
1. Adult males or women who are surgically sterile or postmenopausal, 18 to 55 years of age and can provide written informed consent;
2. Medical history of Type 1 allergies, including rhinitis, asthma, or eczema, or history of asymptomatic skin sensitization following SPTs in the last 2 years;
3. Positive response (greater than or equal to 3 mm of wheal diameter greater than saline control) to 2 common allergens following a skin prick test;
4. If male, agrees to use acceptable contraception.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV);
2. History or presence of alcoholism or drug abuse;
3. History of any significant (as determined by the investigator) drug-related allergic reactions such as, hypersensitivity, anaphylaxis, Stevens-Johnson syndrome;
4. Excessive sun exposure, phototherapy or use of a tanning salon from within 2 weeks prior to Day 1 until the end of study (EOS) visit
5. Clinically significant medical history, of chronic or acute disease or infection
6. Use of any oral or topical medication with anti-inflammatory or antihistamine activity or sleep aids within 7 days prior to Day 1 and through end of the study.
7. Participation in another clinical trial of a drug or device whereby the last investigational drug/device administration is within 30 days prior Day 1 or 5 half-lives, whichever is longer

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
All 3 strengths of the topical treatment and placebo will be applied in a non-randomized manner in designated microzones for all subjects.
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The sample size of up to 24 participants has been selected to provide information on safety and pharmacologic activity of PRN473. No prospective calculations of statistical power have been made.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
22/06/2020
Actual
25/06/2020
Date of last participant enrolment
Anticipated
15/01/2021
Actual
11/08/2020
Date of last data collection
Anticipated
31/01/2021
Actual
14/08/2020
Sample size
Target
24
Accrual to date
Final
21
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 16062 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 29575 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 305162 0
Commercial sector/Industry
Name [1] 305162 0
Principia Biopharma Inc.
Country [1] 305162 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Principia Biopharma Inc.
Address
220 E. Grand Avenue
South San Francisco, CA 94080
Country
United States of America
Secondary sponsor category [1] 305525 0
Commercial sector/Industry
Name [1] 305525 0
Syneos Health
Address [1] 305525 0
159 Port Road Hindmarsh SA 5007
Country [1] 305525 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305529 0
Bellberry Limited
Ethics committee address [1] 305529 0
Ethics committee country [1] 305529 0
Australia
Date submitted for ethics approval [1] 305529 0
04/03/2020
Approval date [1] 305529 0
16/04/2020
Ethics approval number [1] 305529 0

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

Contacts
Principal investigator
Name 100682 0
Prof Sepehr Shakib
Address 100682 0
CMAX Clinical Research
Level 5, 18a North Terrace Adelaide SA 5000
Country 100682 0
Australia
Phone 100682 0
+61 8 7088 7900
Fax 100682 0
Email 100682 0
sepehr.shakib@cmax.com.au
Contact person for public queries
Name 100683 0
Marianne Kavanagh
Address 100683 0
Principia Biopharma Inc.
220 East Grand Avenue
South San Francisco CA 94080
Country 100683 0
United States of America
Phone 100683 0
+16504167775
Fax 100683 0
Email 100683 0
marianne.kavanagh@principiabio.com
Contact person for scientific queries
Name 100684 0
Puneet Arora
Address 100684 0
Principia Biopharma Inc.
220 East Grand Avenue
South San Francisco CA 94080
Country 100684 0
United States of America
Phone 100684 0
+16504022107
Fax 100684 0
Email 100684 0
puneet.arora@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


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
SourceTitleYear of PublicationDOI
Dimensions AIPreclinical Mechanisms of Topical PRN473, a Bruton Tyrosine Kinase Inhibitor, in Immune-Mediated Skin Disease Models2021https://doi.org/10.4049/immunohorizons.2100063
N.B. These documents automatically identified may not have been verified by the study sponsor.