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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02704429




Registration number
NCT02704429
Ethics application status
Date submitted
24/02/2016
Date registered
10/03/2016

Titles & IDs
Public title
A Study of PRN1008 in Adult Patients With Pemphigus Vulgaris
Scientific title
An Open-Label, Phase 2, Pilot Study Investigating the Safety, Clinical Activity, Pharmacokinetics, and Pharmacodynamics of Oral Treatment With the BTK Inhibitor PRN1008 in Patients With Newly Diagnosed or Relapsing Pemphigus Vulgaris
Secondary ID [1] 0 0
2015-003564-37
Secondary ID [2] 0 0
PRN1008-005
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pemphigus Vulgaris 0 0
Condition category
Condition code
Skin 0 0 0 0
Dermatological conditions
Skin 0 0 0 0
Other skin conditions
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PRN1008

Experimental: PRN1008 - Part A: Open-label PRN1008, 12 weeks; 12 weeks follow-up; Part B: Open-label PRN1008, 24 weeks; 4 weeks follow-up


Treatment: Drugs: PRN1008
Part A dosing was initiated administering 400 mg BID. Intrapatient dose adjustments (reductions and increases) were permitted based upon tolerability and clinical response with the maximum dose allowed up to 600 mg BID for 12 weeks.

Part B initial dosing was 400 mg QD for 2 weeks with dose escalation to 400 mg BID at the discretion of the Investigator for the purposes of investigating dose response and identifying the minimal efficacious dose of rilzabrutinib for 24 weeks.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Treatment-emergent Adverse Events
Timepoint [1] 0 0
Part A: until 24 weeks and Part B: until 28 weeks
Primary outcome [2] 0 0
Percentage of Participants Who Are Able to Achieve Control of Disease Activity (CDA) Within 4 Weeks of Starting PRN1008 Treatment Without the Need for Doses of Prednisone or Prednisolone >0.5 mg/kg
Timepoint [2] 0 0
4 weeks
Secondary outcome [1] 0 0
Percentage of Participants Able to Achieve Control of Disease Activity (CDA) Without Corticosteroids Within 4 Weeks
Timepoint [1] 0 0
4 weeks
Secondary outcome [2] 0 0
Percentage of Participants Able to Achieve a Complete Response (CR) Without Corticosteroids
Timepoint [2] 0 0
Part A: 12 weeks treatment and Part B: 24 weeks treatment
Secondary outcome [3] 0 0
Percentage of Participants Able to Achieve Complete Remission (CR) Without the Need for Doses of Prednisone or Prednisolone of Greater Than 0.5mg/kg
Timepoint [3] 0 0
Part A: 12 weeks treatment and Part B: 24 weeks treatment
Secondary outcome [4] 0 0
Time to Control of Disease Activity (CDA)
Timepoint [4] 0 0
Part A: until 24 weeks and Part B: until 28 weeks
Secondary outcome [5] 0 0
Time to End of Consolidation Phase (ECP)
Timepoint [5] 0 0
Part A: until 24 weeks and Part B: until 28 weeks
Secondary outcome [6] 0 0
Time to Complete Remission (CR)
Timepoint [6] 0 0
Part A: until 24 weeks and Part B: until 28 weeks
Secondary outcome [7] 0 0
Time to Relapse After PRN1008 Treatment Discontinuation
Timepoint [7] 0 0
Part A: until 24 weeks and Part B: until 28 weeks
Secondary outcome [8] 0 0
Cumulative Corticosteroid Usage
Timepoint [8] 0 0
Part A: until 24 weeks and Part B: until 28 weeks
Secondary outcome [9] 0 0
Percentage Change From Baseline in Pemphigus Disease Area Index (PDAI) Total Activity Scores
Timepoint [9] 0 0
Part A: until 24 weeks and Part B: until 28 weeks
Secondary outcome [10] 0 0
Change From Baseline in Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) Total Activity Score
Timepoint [10] 0 0
Part A: until 24 weeks and Part B: until 28 weeks
Secondary outcome [11] 0 0
Change From Baseline in Autoimmune Bullous Diseases Quality of Life (ABQOL)
Timepoint [11] 0 0
Part A: until 24 weeks and Part B: until 28 weeks
Secondary outcome [12] 0 0
Change From Baseline in Treatment of Autoimmune Bullous Diseases Quality of Life (TABQOL) Scores
Timepoint [12] 0 0
Part A: until 24 weeks and Part B: until 28 weeks
Secondary outcome [13] 0 0
Change From Baseline in Appetite (SNAQ Score)
Timepoint [13] 0 0
Part A: until 24 weeks and Part B: until 28 weeks

Eligibility
Key inclusion criteria
* Male or female patients, aged 18 to 80 years old, with biopsy-proven, mild-moderate PV (PDAI 8 to 45) in Part A and mild to severe PV in Part B (PDAI 8 to 60) that are either:

* newly diagnosed patients (i.e. naïve to an effective induction treatment regimen) for whom an initial period of PRN1008 monotherapy is judged clinically acceptable, or
* relapsing patients, for whom an initial period of PRN1008 monotherapy, or combination therapy with any of low dose corticosteroid, ie.0.5 mg/kg of prednis(ol)one per day
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Pregnant or lactating women
* A history of malignancy of any type, other than surgically excised non-melanoma skin cancers or in situ cervical cancer within 5 years before the day of dosing
* Use of immunologic response modifiers with the following periods prior to Day 1: 1 week: cyclophosphamide; 4 weeks: intravenous immunoglobulin, Kinaret (anakinra) and Enbrel (etanercept); 12 weeks: Remicade (infliximab), Humira (adalimumab), Simponi (golimumab), Orencia (abatacept), Actemra (tocilizumab), Cimzia (certolizumab), Cosentyx (secukinumab), plasmapheresis; 6 months: Rituxan/MabThera (rituximab), ofatumumab, any other anti-CD20 antibody, other long acting biologics
* More than 0.5 mg/kg of prednis(ol)one per day ("low dose corticosteroids") within the two weeks prior to Day 1
* Use of proton pump inhibitor drugs such as omeprazole and esomeprazole
* Has received any investigational drug (or is currently using an investigational device) within the 30 days before receiving the first dose of study medication, or at least 5 times the respective elimination half-life time (whichever is longer)
* History of drug abuse within the precious 12 months
* Alcoholism or excessive alcohol use, defined as regular consumption of more than approximately 3 standard drinks per day
* Refractory nausea and vomiting, malabsorption, external biliary shunt, significant bowel resection that would preclude adequate study drug absorption
* History of anorexia nervosa or periods of three months or more of low body weight in the past 5 years
* Donation of a unit or more of blood or blood products within 4 weeks prior to Day 1
* History of solid organ transplant
* History of epilepsy or other forms of seizures in the last 5 years
* Positive for screening for human immunodeficiency virus, hepatitis B (surface and core antibodies unrelated to vaccination), or hepatitis C (anti-HCV antibody confirmed with Hep C RNA)
* History of active or latent tuberculosis (TB) infection (must test negative using the QuantiFERON test to be eligible)
* History of serious infections requiring intravenous (by catheter that delivers antibiotics into your blood) treatment
* Live vaccine within 28 days prior to baseline or plan to receive one during the study

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



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
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)
NSW,VIC
Recruitment hospital [1] 0 0
Premier Specialists - Kogarah
Recruitment hospital [2] 0 0
Sinclair Dermatology - East Melbourne
Recruitment hospital [3] 0 0
Royal Melbourne, Dermatology Office - Melbourne
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
3002 - East Melbourne
Recruitment postcode(s) [3] 0 0
3050 - Melbourne
Recruitment outside Australia
Country [1] 0 0
Croatia
State/province [1] 0 0
Osijek
Country [2] 0 0
Croatia
State/province [2] 0 0
Zagreb
Country [3] 0 0
France
State/province [3] 0 0
Siene-Saint Denis
Country [4] 0 0
France
State/province [4] 0 0
Rouen
Country [5] 0 0
Greece
State/province [5] 0 0
Ioannina
Country [6] 0 0
Greece
State/province [6] 0 0
Thessaly
Country [7] 0 0
Greece
State/province [7] 0 0
Athens
Country [8] 0 0
Greece
State/province [8] 0 0
Thessaloniki
Country [9] 0 0
Israel
State/province [9] 0 0
Ramat-Gan
Country [10] 0 0
Israel
State/province [10] 0 0
Tel Aviv

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Principia Biopharma, a Sanofi Company
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Principia Biopharma Australia Pty Ltd.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.