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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03762265




Registration number
NCT03762265
Ethics application status
Date submitted
29/11/2018
Date registered
3/12/2018

Titles & IDs
Public title
A Study of PRN1008 in Patients With Pemphigus
Scientific title
A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial to Evaluate the Efficacy and Safety of Oral BTK Inhibitor Rilzabrutinib (PRN1008) in Moderate to Severe Pemphigus
Secondary ID [1] 0 0
PRN1008-012
Secondary ID [2] 0 0
EFC17092
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pemphigus 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 - Rilzabrutinib
Treatment: Drugs - Placebo

Placebo comparator: Placebo Then Rilzabrutinib - In BT period, participants received placebo orally twice daily (BID) up to 37 weeks along with sponsor-provided corticosteroids (CS). After at least two weeks of control of disease activity (CDA; no new lesions and established lesions begin to heal), based on protocol-specified clinical criteria, investigators could decrease the CS dose to a minimum of 5 milligrams (mg) prednisone/prednisolone per day from Week 29 to Week 37. Post completion of BT period, eligible participants received rilzabrutinib 400 mg BID up to Week 61 in OLE period and those who were eligible after OLE period completion, continued the same treatment until Week 109 in LTE period according to protocol-specified criteria.

Experimental: Rilzabrutinib Then Rilzabrutinib - In BT period, participants received rilzabrutinib 400 mg orally BID up to 37 weeks along with sponsor-provided CS. After at least two weeks of CDA (no new lesions and established lesions begin to heal), based on protocol-specified clinical criteria, investigators could decrease the CS dose to a minimum of 5 mg prednisone/prednisolone per day from Week 29 to Week 37. Post completion of BT period, eligible participants received rilzabrutinib 400 mg BID up to Week 61 in OLE period and those who were eligible after OLE period completion, continued the same treatment until Week 109 in LTE period according to protocol-specified criteria.


Treatment: Drugs: Rilzabrutinib
Pharmaceutical form: Tablet Route of administration: Oral

Treatment: Drugs: Placebo
Pharmaceutical form: Tablet Route of administration: Oral

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

Outcomes
Primary outcome [1] 0 0
Percentage of Participants Who Achieved Complete Remission (CR) With a Corticosteroids Dose of Less Than or Equal to (<=) 10 mg/Day From Week 29 to Week 37: Pemphigus Vulgaris Participants in Modified Intent-to-Treat (PV mITT) Population
Timepoint [1] 0 0
From Week 29 to Week 37
Primary outcome [2] 0 0
Percentage of Participants Who Achieved Complete Remission With a Corticosteroids Dose of <=10 mg/Day From Week 29 to Week 37: Modified Intent-to-Treat (mITT) Population
Timepoint [2] 0 0
From Week 29 to Week 37
Secondary outcome [1] 0 0
Cumulative Oral Corticosteroid Dose From Baseline to Week 37: PV mITT Population
Timepoint [1] 0 0
Baseline to Week 37
Secondary outcome [2] 0 0
Cumulative Oral Corticosteroid Dose From Baseline to Week 37: mITT Population
Timepoint [2] 0 0
Baseline to Week 37
Secondary outcome [3] 0 0
Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: PV mITT Population
Timepoint [3] 0 0
Baseline to Week 37
Secondary outcome [4] 0 0
Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: mITT Population
Timepoint [4] 0 0
Baseline to Week 37
Secondary outcome [5] 0 0
Time to First Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: PV mITT Population
Timepoint [5] 0 0
Baseline to Week 37
Secondary outcome [6] 0 0
Time to First Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: mITT Population
Timepoint [6] 0 0
Baseline to Week 37
Secondary outcome [7] 0 0
Percentage of Participants Who Achieved Complete Remission With a Corticosteroids Dose of <=5 mg/Day From Week 29 to Week 37: PV mITT Population
Timepoint [7] 0 0
From Week 29 to Week 37
Secondary outcome [8] 0 0
Percentage of Participants Who Achieved Complete Remission With a Corticosteroids Dose of <=5 mg/Day From Week 29 to Week 37: mITT Population
Timepoint [8] 0 0
From Week 29 to Week 37
Secondary outcome [9] 0 0
Percentage of Participants Who Had Pemphigus Disease Area Index (PDAI) Score <3 With a Corticosteroids Dose <=10 mg/Day From Week 29 to Week 37: PV mITT Population
Timepoint [9] 0 0
From Week 29 to Week 37
Secondary outcome [10] 0 0
Percentage of Participants Who Had Pemphigus Disease Area Index Score <3 With a Corticosteroids Dose <=10 mg/Day From Week 29 to Week 37: mITT Population
Timepoint [10] 0 0
From Week 29 to Week 37
Secondary outcome [11] 0 0
Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Weeks 61 and 109: PV mITT Population
Timepoint [11] 0 0
Baseline to Week 61 and Baseline to Week 109
Secondary outcome [12] 0 0
Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Weeks 61 and 109: mITT Population
Timepoint [12] 0 0
Baseline to Weeks 61 and Baseline to Week 109
Secondary outcome [13] 0 0
Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Baseline to Weeks 61 and 109: PV mITT Population
Timepoint [13] 0 0
Baseline to Week 61 and Baseline to Week 109
Secondary outcome [14] 0 0
Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Baseline to Weeks 61 and 109: mITT Population
Timepoint [14] 0 0
Baseline to Week 61 and Baseline to Week 109
Secondary outcome [15] 0 0
Glucocorticoid Toxicity Index (GTI) - Cumulative Worsening Score (CWS) and Aggregate Improvement Score (AIS) at Week 37: PV mITT Population
Timepoint [15] 0 0
At Week 37
Secondary outcome [16] 0 0
Glucocorticoid Toxicity Index - Cumulative Worsening Score and Aggregate Improvement Score at Week 37: mITT Population
Timepoint [16] 0 0
At Week 37
Secondary outcome [17] 0 0
Change From Baseline in Pemphigus Disease Area Index Score at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population
Timepoint [17] 0 0
Baseline, Weeks 5, 13, 25, 37, 61, and 109
Secondary outcome [18] 0 0
Change From Baseline in Pemphigus Disease Area Index Score at Weeks 5, 13, 25, 37, 61, and 109: mITT Population
Timepoint [18] 0 0
Baseline, Weeks 5, 13, 25, 37, 61, and 109
Secondary outcome [19] 0 0
Change From Baseline in Autoimmune Bullous Disease Quality of Life (ABQOL) Score at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population
Timepoint [19] 0 0
Baseline, Weeks 5, 13, 25, 37, 61, and 109
Secondary outcome [20] 0 0
Change From Baseline in Autoimmune Bullous Disease Quality of Life Score at Weeks 5, 13, 25, 37, 61, and 109: mITT Population
Timepoint [20] 0 0
Baseline, Weeks 5, 13, 25, 37, 61, and 109
Secondary outcome [21] 0 0
Percentage of Participants With Autoimmune Bullous Disease Quality of Life Score of Zero at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population
Timepoint [21] 0 0
At Weeks 5, 13, 25, 37, 61, and 109
Secondary outcome [22] 0 0
Percentage of Participants With Autoimmune Bullous Disease Quality of Life Score of Zero at Weeks 5, 13, 25, 37, 61, and 109: mITT Population
Timepoint [22] 0 0
At Weeks 5, 13, 25, 37, 61, and 109
Secondary outcome [23] 0 0
Change From Baseline in the European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) Score: Visual Analogue Scale (VAS) Scores at Weeks 5, 13, 25, 37, 61, and 109
Timepoint [23] 0 0
Baseline, Weeks 5, 13, 25, 37, 61, and 109
Secondary outcome [24] 0 0
Change From Baseline in the European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels Score: Individual Dimension at Weeks 5, 13, 25, 37, 61, and 109
Timepoint [24] 0 0
Baseline, Weeks 5, 13, 25, 37, 61, and 109
Secondary outcome [25] 0 0
Time to First Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Weeks 61 and 109
Timepoint [25] 0 0
Baseline to Week 61 and Baseline to Week 109
Secondary outcome [26] 0 0
Total Number of Disease Relapses/Flares From Initial Control of Disease Activity (CDA) to Week 37: PV mITT Population
Timepoint [26] 0 0
From initial CDA up to Week 37 (i.e., during any time from Baseline up to Week 37)
Secondary outcome [27] 0 0
Total Number of Disease Relapses/Flares From Initial Control of Disease Activity to Week 37: mITT Population
Timepoint [27] 0 0
From initial CDA up to Week 37 (i.e., during any time from Baseline up to Week 37)
Secondary outcome [28] 0 0
Time to Initial Relapse/Flare From Initial Control of Disease Activity to Week 37: PV mITT Population
Timepoint [28] 0 0
From initial CDA up to Week 37 (i.e., during any time from Baseline up to Week 37)
Secondary outcome [29] 0 0
Time to Initial Relapse/Flare From Initial Control of Disease Activity to Week 37: mITT Population
Timepoint [29] 0 0
From initial CDA up to Week 37 (i.e., during any time from Baseline up to Week 37)
Secondary outcome [30] 0 0
Percentage of Participants With 3 or More New Lesions Within 1 Month That do Not Heal Spontaneously Within 1 Week, or With Extension of Established Lesions at Week 37: PV mITT Population
Timepoint [30] 0 0
At Week 37
Secondary outcome [31] 0 0
Percentage of Participants With 3 or More New Lesions Within 1 Month That do Not Heal Spontaneously Within 1 Week, or With Extension of Established Lesions at Week 37: mITT Population
Timepoint [31] 0 0
At Week 37
Secondary outcome [32] 0 0
Percentage of Participants With at Least One Disease Relapse/Flare From Initial Control of Disease Activity to Week 37: PV mITT Population
Timepoint [32] 0 0
From initial CDA up to Week 37 (i.e., during any time from Baseline up to Week 37)
Secondary outcome [33] 0 0
Percentage of Participants With at Least One Disease Relapse/Flare From Initial Control of Disease Activity to Week 37: mITT Population
Timepoint [33] 0 0
From initial CDA up to Week 37 (i.e., during any time from Baseline up to Week 37)
Secondary outcome [34] 0 0
Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Week 37 to Week 61: PV mITT Population
Timepoint [34] 0 0
From Week 37 to Week 61
Secondary outcome [35] 0 0
Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Week 37 to Week 61: mITT Population
Timepoint [35] 0 0
From Week 37 to Week 61
Secondary outcome [36] 0 0
Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Week 37 to Week 61: PV mITT Population
Timepoint [36] 0 0
From Week 37 to Week 61
Secondary outcome [37] 0 0
Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Week 37 to Week 61: mITT Population
Timepoint [37] 0 0
From Week 37 to Week 61
Secondary outcome [38] 0 0
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Timepoint [38] 0 0
BT Period: From Day 1 of Week 1 to Week 37, OLE Period: from Week 37 to Week 61 and LTE Period: from Week 61 up to 4 weeks after the last dose at Week 109 (i.e., up to Week 113)
Secondary outcome [39] 0 0
Pharmacokinetics (PK): Plasma Concentration of Rilzabrutinib
Timepoint [39] 0 0
Pre-dose and 2 hours post-dose on Day 1
Secondary outcome [40] 0 0
Pharmacodynamics (PD): Change From Baseline in Antibody Levels - Anti-desmoglein 1 (Anti-dsg 1) and Anti-desmoglein 3 (Anti-dsg 3) at Weeks 13, 25, 37, 49, 61, 73, 85, 97, and 109: PV mITT Population
Timepoint [40] 0 0
Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, and 109
Secondary outcome [41] 0 0
Pharmacodynamics: Change From Baseline in Antibody Levels - Anti-desmoglein 1 (Anti-dsg 1) and Anti-desmoglein 3 (Anti-dsg 3) at Weeks 13, 25, 37, 49, 61, 73, 85, 97 and 109: mITT Population
Timepoint [41] 0 0
Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, and 109

Eligibility
Key inclusion criteria
* Male or female participants, aged 18 to 80 years old with moderate to severe, newly diagnosed or relapsing PV or PF, with a clinical presentation and histopathology consistent with PV or PF.
* Positive circulating anti-desmoglein 1 (anti-dsg1) or 3 autoantibody titer.
* At screening, pemphigus disease area index score of at least 9 points for relapsing participants or at least 15 points for newly diagnosed participants.
* Adequate hematologic, hepatic, and renal function.
* Effective means of contraception.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Suspected paraneoplastic pemphigus and other forms of pemphigus that were not PV or PF.
* Previous use of a Bruton tyrosine kinase inhibitor.
* Pregnant or lactating women.
* Electrocardiogram clinically significant abnormalities.
* A history of malignancy of any type within 5 years before Day 1, other than surgically excised non-melanoma skin cancers or in situ cervical cancer.
* Use of immunologic response modifiers as concomitant medication and with the washout period.
* Use of proton pump inhibitor drugs such as omeprazole and esomeprazole within 3 days of Day 1.
* Concomitant use of known strong-to-moderate inducers or inhibitors of cytochrome P450 3A (CYP3A) within 3 days or 5 half-lives (whichever is longer) of Day 1
* Use of CYP3A-sensitive substrate drugs.
* Had received any investigational drug within the 30 days before Day 1.
* History of drug abuse within the previous 12 months.
* Alcoholism or excessive alcohol use.
* Any other clinically significant disease, condition or medical history that, in the opinion of the Investigator, would interfere with participant safety, trial evaluations, and/or trial procedures.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
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)
WA
Recruitment hospital [1] 0 0
Central Recruiting (Principia Biopharma) - Fremantle
Recruitment hospital [2] 0 0
Central Recruiting (Principia Biopharma) - Melbourne
Recruitment hospital [3] 0 0
Central Recruiting (Principia Biopharma) - Sydney
Recruitment postcode(s) [1] 0 0
6160 - Fremantle
Recruitment postcode(s) [2] 0 0
3050 - Melbourne
Recruitment postcode(s) [3] 0 0
2217 - Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Michigan
Country [4] 0 0
United States of America
State/province [4] 0 0
Minnesota
Country [5] 0 0
United States of America
State/province [5] 0 0
New Mexico
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Ohio
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Utah
Country [11] 0 0
Argentina
State/province [11] 0 0
Buenos Aires
Country [12] 0 0
Argentina
State/province [12] 0 0
San Nicolás
Country [13] 0 0
Brazil
State/province [13] 0 0
Campinas
Country [14] 0 0
Brazil
State/province [14] 0 0
Campo Grande
Country [15] 0 0
Brazil
State/province [15] 0 0
Ribeirão Preto
Country [16] 0 0
Bulgaria
State/province [16] 0 0
Pleven
Country [17] 0 0
Bulgaria
State/province [17] 0 0
Plovdiv
Country [18] 0 0
Bulgaria
State/province [18] 0 0
Sofia
Country [19] 0 0
Canada
State/province [19] 0 0
Manitoba
Country [20] 0 0
Croatia
State/province [20] 0 0
Osijek
Country [21] 0 0
Croatia
State/province [21] 0 0
Zagreb
Country [22] 0 0
France
State/province [22] 0 0
Bobigny
Country [23] 0 0
France
State/province [23] 0 0
Bordeaux
Country [24] 0 0
France
State/province [24] 0 0
Lille
Country [25] 0 0
France
State/province [25] 0 0
Pierre-Bénite
Country [26] 0 0
France
State/province [26] 0 0
Rouen
Country [27] 0 0
France
State/province [27] 0 0
Toulouse
Country [28] 0 0
Germany
State/province [28] 0 0
Berlin
Country [29] 0 0
Germany
State/province [29] 0 0
Dresden
Country [30] 0 0
Germany
State/province [30] 0 0
Düsseldorf
Country [31] 0 0
Germany
State/province [31] 0 0
Erlangen
Country [32] 0 0
Germany
State/province [32] 0 0
Heidelberg
Country [33] 0 0
Germany
State/province [33] 0 0
Kiel
Country [34] 0 0
Germany
State/province [34] 0 0
Lübeck
Country [35] 0 0
Germany
State/province [35] 0 0
Münster
Country [36] 0 0
Greece
State/province [36] 0 0
Athens
Country [37] 0 0
Greece
State/province [37] 0 0
Ioánnina
Country [38] 0 0
Greece
State/province [38] 0 0
Larisa
Country [39] 0 0
Greece
State/province [39] 0 0
Thessaloníki
Country [40] 0 0
Israel
State/province [40] 0 0
Be'er Sheva
Country [41] 0 0
Israel
State/province [41] 0 0
Haifa
Country [42] 0 0
Israel
State/province [42] 0 0
Ramat Gan
Country [43] 0 0
Israel
State/province [43] 0 0
Tel Aviv
Country [44] 0 0
Italy
State/province [44] 0 0
Brescia
Country [45] 0 0
Italy
State/province [45] 0 0
Catania
Country [46] 0 0
Italy
State/province [46] 0 0
Florence
Country [47] 0 0
Italy
State/province [47] 0 0
Milan
Country [48] 0 0
Italy
State/province [48] 0 0
Padova
Country [49] 0 0
Italy
State/province [49] 0 0
Parma
Country [50] 0 0
Italy
State/province [50] 0 0
Rome
Country [51] 0 0
Italy
State/province [51] 0 0
Torino
Country [52] 0 0
Poland
State/province [52] 0 0
Gdansk
Country [53] 0 0
Poland
State/province [53] 0 0
Kraków
Country [54] 0 0
Poland
State/province [54] 0 0
Lublin
Country [55] 0 0
Poland
State/province [55] 0 0
Warsaw
Country [56] 0 0
Poland
State/province [56] 0 0
Wroclaw
Country [57] 0 0
Serbia
State/province [57] 0 0
Belgrade
Country [58] 0 0
Serbia
State/province [58] 0 0
Novi Sad
Country [59] 0 0
Spain
State/province [59] 0 0
Barcelona
Country [60] 0 0
Spain
State/province [60] 0 0
Córdoba
Country [61] 0 0
Spain
State/province [61] 0 0
Madrid
Country [62] 0 0
Spain
State/province [62] 0 0
Pamplona
Country [63] 0 0
Taiwan
State/province [63] 0 0
Dalin
Country [64] 0 0
Taiwan
State/province [64] 0 0
Kaohsiung
Country [65] 0 0
Taiwan
State/province [65] 0 0
Taipei
Country [66] 0 0
Turkey
State/province [66] 0 0
Fatih
Country [67] 0 0
Turkey
State/province [67] 0 0
Istanbul
Country [68] 0 0
Turkey
State/province [68] 0 0
Konyaalti
Country [69] 0 0
Turkey
State/province [69] 0 0
Merkez
Country [70] 0 0
Ukraine
State/province [70] 0 0
Dnipro
Country [71] 0 0
Ukraine
State/province [71] 0 0
Kyiv
Country [72] 0 0
Ukraine
State/province [72] 0 0
Lviv
Country [73] 0 0
Ukraine
State/province [73] 0 0
Zaporizhzhya
Country [74] 0 0
United Kingdom
State/province [74] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Principia Biopharma, a Sanofi Company
Address
Country

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Address 0 0
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.