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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02704429
Ethics application status
Date submitted
24/02/2016
Date registered
10/03/2016
Date last updated
4/03/2020

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
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 week follow up; Part B: Open-label PRN1008, 24 weeks;4 weeks follow up


Treatment: Drugs: PRN1008
Part A: PRN1008, oral dose, 12 weeks; Part B: PRN1008, oral dose 24 weeks

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

Outcomes
Primary outcome [1] 0 0
Incidence of treatment-emergent adverse events - The incidence of treatment-emergent adverse events (TEAEs), including clinically significant changes in physical examination, laboratory tests, and vital signs.
Timepoint [1] 0 0
Part A: 24 week treatment
Primary outcome [2] 0 0
Control of disease activity at 4 weeks - The proportion of subjects 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 treatment
Secondary outcome [1] 0 0
Time to control of disease activity (CDA) - Time to control of disease activity (CDA) defined in EADV 2015 Pemphigus S2 Guideline
Timepoint [1] 0 0
Part A: 12 week treatment; 12 week follow up and Part B: 24 week treatment, 4 week follow-up
Secondary outcome [2] 0 0
Time to end of consolidation phase - Time to end of consolidation phase as defined in EADV 2015 Pemphigus S2 Guideline
Timepoint [2] 0 0
Part A: 12 week treatment; 12 week follow up and Part B: 24 week treatment, 4 week follow-up
Secondary outcome [3] 0 0
Time to complete response - Time to complete response as defined in EADV 2015 Pemphigus S2 Guideline
Timepoint [3] 0 0
Part A: 12 week treatment; 12 week follow up and Part B: 24 week treatment, 4 week follow-up
Secondary outcome [4] 0 0
Time to relapse after PRN1008 treatment discontinuation - Time to relapse after PRN1008 treatment discontinuation
Timepoint [4] 0 0
Part A: 12 week follow up and Part B: 4 week follow-up
Secondary outcome [5] 0 0
Cumulative corticosteroid usage - Cumulative corticosteroid usage
Timepoint [5] 0 0
Part A: 12 week treatment; 12 week follow up and Part B: 24 week treatment, 4 week follow-up

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 (= 10 mg/day),
Minimum age
18 Years
Maximum age
80 Years
Gender
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

- Use of >10 mg per day of oral prednisolone per day within 2 weeks prior to Day 1
(inhaled and mucosal [for symptomatic treatment of oral lesions] corticosteroids are
allowed)

- 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 there months or more of low body weight
(BMI<17.5)

- 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
N/A
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 Inc.
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
Open-label cohort study in adult patients with newly diagnosed or relapsing pemphigus
vulgaris, with intra-patient dose-adjustment based on clinical response and BTK occupancy,
and with conventional immunosuppressive "rescue treatment", if indicated. The duration of
therapy in Part A will be 12 weeks, followed by 12 weeks of follow up. The extension phase,
Part B includes 24 weeks of therapy, followed by 4 weeks of follow-up.
Trial website
https://clinicaltrials.gov/show/NCT02704429
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Dolca Thomas, MD
Address 0 0
Principia Biopharma
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

Summary results
Other publications