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A Study of PRN1008 in Patients With Pemphigus

Primary Purpose

Pemphigus

Status

Terminated

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Rilzabrutinib

Placebo

About this trial

This is an interventional treatment trial for Pemphigus focused on measuring Pemphigus Vulgaris (PV), Pemphigus Foliaceus (PF)

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

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.

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo Then Rilzabrutinib

Rilzabrutinib Then Rilzabrutinib

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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

Complete remission was defined as absence of new and established lesions and was intended to mean "no disease activity" for 2 consecutive weeks, with Pemphigus Disease Area Index (PDAI) activity score =0 and CS dose <=10 mg. PDAI score weighted for number and size of lesions with score of 0 (absent) to 10 given for skin (12 body locations), scalp and mucous membrane showing disease activity (erosions/blisters or new erythema). PDAI total score ranged from 0 to 250 points representing disease activity (120 points for skin activity; 10 points for scalp activity; 120 points for mucosal activity). Higher score indicated more disease activity. In this outcome measure (OM), percentage of participants who achieved CR while on a daily corticosteroids dose of <=10 mg/day were reported.

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

Complete remission was defined as absence of new and established lesions and was intended to mean "no disease activity" for 2 consecutive weeks, with PDAI activity score =0 and CS dose <=10 mg. PDAI score weighted for number and size of lesions with score of 0 (absent) to 10 given for skin (12 body locations), scalp and mucous membrane showing disease activity (erosions/blisters or new erythema). PDAI total score ranged from 0 to 250 points representing disease activity (120 points for skin activity; 10 points for scalp activity; 120 points for mucosal activity). Higher score indicated more disease activity. In this OM, percentage of participants who achieved CR while on a daily corticosteroids dose of <=10 mg/day were reported.

Secondary Outcome Measures

Cumulative Oral Corticosteroid Dose From Baseline to Week 37: PV mITT Population

The cumulative dose (in milligrams) of sponsor-provided oral CS (prednisone or prednisolone) received by the participants during the BT period was calculated from Baseline to Week 37 and is reported in this OM.

Cumulative Oral Corticosteroid Dose From Baseline to Week 37: mITT Population

Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: PV mITT Population

Cumulative duration (in days) of CR post first CS dose of <= 10 mg/day from Baseline to Week 37 was analyzed with a zero-inflated negative binomial model with terms of treatment group and disease history, and an offset based on the number of days on blinded treatment period and were reported in this OM. Complete remission was defined as the absence of new and established lesions and was intended to mean "no disease activity".

Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: mITT Population

Time to First Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: PV mITT Population

Time to first CR was the time (in days) to achieve CR while on CS dose of <=10 mg/day. Complete remission was defined as the absence of new and established lesions to the "no disease activity". Kaplan-Meier method was used for the analysis.

Time to First Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: mITT Population

Percentage of Participants Who Achieved Complete Remission With a Corticosteroids Dose of <=5 mg/Day From Week 29 to Week 37: PV mITT Population

Complete remission was defined as the absence of new and established lesions and was intended to mean "no disease activity". In this OM, percentage of participants who achieved CR while on a daily corticosteroids dose of <=5 mg/day were reported.

Percentage of Participants Who Achieved Complete Remission With a Corticosteroids Dose of <=5 mg/Day From Week 29 to Week 37: mITT Population

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

PDAI is specific cutaneous and mucosal disease activity assessment performed by investigator based on evaluation of lesions in well-defined anatomical locations. The score weighted for the number and size of lesions with score of 0 (absent) to 10 given for skin (12 body locations), scalp and mucous membrane showing disease activity (erosions/blisters or new erythema). Thus, PDAI total activity score ranged from 0 to 250 points representing disease activity (120 points for skin activity; 10 points for scalp activity; 120 points for mucosal activity). Higher score indicated more disease activity. In this OM, participants with PDAI score <3 while on a CS dose of <=10 mg/day were reported.

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

Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Weeks 61 and 109: PV mITT Population

Cumulative duration (in days) of CR post all doses of CS <=10 mg/day during Baseline to Week 61 and Baseline to Week 109 were reported in this OM. Complete remission was defined as the absence of new and established lesions to the "no disease activity".

Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Weeks 61 and 109: mITT Population

Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Baseline to Weeks 61 and 109: PV mITT Population

Cumulative duration (in days) of CR post all doses of CS =0 mg/day during Baseline to Week 61 and Baseline to Week 109 were reported in this OM. Complete remission was defined as the absence of new and established lesions to the "no disease activity".

Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Baseline to Weeks 61 and 109: mITT Population

Cumulative duration (in days) of CR post all doses of CS dose = 0 mg/day during Baseline to Week 61 and Baseline to Week 109 were reported in this OM. Complete remission was defined as the absence of new and established lesions to the "no disease activity".

Glucocorticoid Toxicity Index (GTI) - Cumulative Worsening Score (CWS) and Aggregate Improvement Score (AIS) at Week 37: PV mITT Population

GTI assessed glucocorticoid (GC) related morbidity and GC-sparing ability of other therapies; composed of 2 components: Composite GTI and specific list. Composite GTI had 9 domains and specific list had 23 items (11 domains), used as complementary tool to C-GTI. Composite GTI score:sum of 9 domain-specific scores at each visit and cumulative GTI score:sum of composite GTI scores across each visit. 2 cumulative GTI scores: CWS and AIS at Week 37 reported in this OM. CWS assessed cumulative GC toxicity regardless of whether toxicity had lasting effects/was transient. AIS assessed new therapy effectiveness in decreasing any Baseline GC toxicity over time. CWS composite score range: 0 to 439 and AIS composite score range: -346 to 439. In CWS and AIS, minimum score=least toxicity and maximum score=most toxicity. Least square (LS) mean and standard error (SE) from analysis of covariance model using treatment, disease history as fixed effects and Baseline GTI score and CS dose as covariates.

Glucocorticoid Toxicity Index - Cumulative Worsening Score and Aggregate Improvement Score at Week 37: mITT Population

GTI assessed GC related morbidity and GC-sparing ability of other therapies; composed of 2 components: Composite GTI and specific list. Composite GTI contained 9 domains and specific list contained of 23 items (11 domains), used as complementary tool to C-GTI. Composite GTI score: sum of 9 domain-specific scores at each visit and cumulative GTI score: sum of composite GTI scores across each visit. Two cumulative GTI scores: CWS and AIS at Week 37 were reported in this OM. CWS assessed cumulative GC toxicity regardless of whether toxicity had lasting effects/was transient. AIS assessed new therapy effectiveness in decreasing any Baseline GC toxicity over time. CWS composite score ranged from 0 to 439 and AIS composite score ranged from -346 to 439. For CWS and AIS, minimum score = least toxicity and maximum score = most toxicity. LS mean and SE from analysis of covariance model using treatment, disease history as fixed effects and Baseline GTI score and CS dose as covariates.

Change From Baseline in Pemphigus Disease Area Index Score at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population

PDAI is specific cutaneous and mucosal disease activity assessment performed by investigator based on evaluation of lesions in well-defined anatomical locations. The score weighted for the number and size of lesions with score of 0 (absent) to 10 given for skin (12 body locations), scalp and mucous membrane showing disease activity (erosions/blisters or new erythema). Thus, PDAI total activity score ranged from 0 to 250 points representing disease activity (120 points for skin activity; 10 points for scalp activity; 120 points for mucosal activity). Higher score indicated more disease activity. PDAI activity score was measured independently of the CS dose administered in the participants.

Change From Baseline in Pemphigus Disease Area Index Score at Weeks 5, 13, 25, 37, 61, and 109: mITT Population

PDAI is specific cutaneous and mucosal disease activity assessment performed by investigator based on evaluation of lesions in well-defined anatomical locations. The score weighted for the number and size of lesions with score of 0 (absent) to 10 given for skin (12 body locations), scalp and mucous membrane showing disease activity (erosions/blisters or new erythema). Thus, PDAI total activity score ranged from 0 to 250 points representing disease activity (120 points for skin activity; 10 points for scalp activity; 120 points for mucosal activity). Higher score indicated more disease activity. PDAI activity score was measured independently of the CS dose administered in the participants.

Change From Baseline in Autoimmune Bullous Disease Quality of Life (ABQOL) Score at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population

ABQOL, a 17-item questionnaire is a valid and reliable tool to assess quality of life in participants with autoimmune blistering diseases. Each question score ranged from 0 to 3 points, 0 = never, 1 = occasionally, 2 = sometimes and 3 = all the time, where higher score = poor QOL. The total ABQoL score was calculated by summing the score of each question and it ranged from 0 to 51, where higher score = more QOL impairment.

Change From Baseline in Autoimmune Bullous Disease Quality of Life Score at Weeks 5, 13, 25, 37, 61, and 109: mITT Population

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

Percentage of Participants With Autoimmune Bullous Disease Quality of Life Score of Zero at Weeks 5, 13, 25, 37, 61, and 109: mITT Population

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

EQ-5D-5L: standardized measure of health status that provides general assessment of health and wellbeing. EQ-5D VAS was used to record a participant's rating for his/her current health-related quality of life state and captured on a vertical VAS scale ranging from 0 to 100, where 0=worst imaginable health state and 100=best imaginable health state, where higher states indicated better outcomes.

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

EQ-5D-5L: standardized measure of health status that provides general assessment of health and wellbeing. The EQ-5D descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has a 5-level response: no problems, slight problems, moderate problems, severe problems, and extreme problems. Response options are measured with a 5-point Likert scale (for the 5L version). The 5D-5L systems are converted into a single index utility score between 0 to 1, where higher score indicates a better health state and lower score indicate worse health state.

Time to First Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Weeks 61 and 109

Time to first CR was the time (in days) to achieve CR while on a CS dose of <=10 mg/day from Baseline to Week 61 and from Baseline to Week 109. Complete remission was defined as absence of new and established lesions to the "no disease activity".

Total Number of Disease Relapses/Flares From Initial Control of Disease Activity (CDA) to Week 37: PV mITT Population

Total Number of Disease Relapses/Flares which occurred from initial CDA to Week 37 were reported. CDA was defined as disappearance of new lesions cease to form and established lesions begin to heal. Relapse/flare was defined by the appearance of 3 or more new lesions after CDA and within a month that do not heal spontaneously within 1 week, or by the extension of established lesions, in a participant who had achieved CDA.

Total Number of Disease Relapses/Flares From Initial Control of Disease Activity to Week 37: mITT Population

Time to Initial Relapse/Flare From Initial Control of Disease Activity to Week 37: PV mITT Population

Time duration (in days) from the time of initial relapse/flare which occurred from initial CDA up to Week 37 were reported in this OM. CDA was defined as the visit at which new lesions cease to form and established lesions begin to heal. Relapse/flare was defined by the appearance of 3 or more new lesions after CDA and within a month that do not heal spontaneously within 1 week, or by the extension of established lesions, in a participant who had achieved CDA. Kaplan-Meier method was used for the analysis.

Time to Initial Relapse/Flare From Initial Control of Disease Activity to Week 37: mITT Population

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

Percentage of Participants With 3 or More New Lesions Within past 1 month that do not heal spontaneously within past 1 week, or with extension of established lesions, were assessed at Week 37 and reported in this OM.

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

Percentage of participants with 3 or more new lesions within past 1 month that do not heal spontaneously within past 1 week, or with extension of established lesions, were assessed at Week 37 and reported in this OM.

Percentage of Participants With at Least One Disease Relapse/Flare From Initial Control of Disease Activity to Week 37: PV mITT Population

CDA was defined as the visit at which new lesions cease to form and established lesions begin to heal. Disease relapse/flare was defined by the appearance of 3 or more new lesions after CDA and within a month that do not heal spontaneously within 1 week, or by the extension of established lesions, in a participant who had achieved CDA. Percentages were calculated based on number of participants assessed (i.e. participants achieved CDA) in each treatment group. Percentage of participants with at least one disease relapse/flare from Initial CDA to Week 37 were reported in this OM.

Percentage of Participants With at Least One Disease Relapse/Flare From Initial Control of Disease Activity to Week 37: mITT Population

Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Week 37 to Week 61: PV mITT Population

Cumulative duration (in days) of CR post first dose of CS <=10 mg/day from Week 37 to Week 61 were reported in this OM. Complete remission was defined as the absence of new and established lesions and was intended to mean "no disease activity".

Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Week 37 to Week 61: mITT Population

Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Week 37 to Week 61: PV mITT Population

Cumulative duration (in days) of CR post first dose of CS = 0 mg/day from Week 37 to Week 61 were reported in this OM. Complete remission was defined as the absence of new and established lesions and was intended to mean "no disease activity".

Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Week 37 to Week 61: mITT Population

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug and does not necessarily had to have a causal relationship with the treatment. Serious AEs (SAEs) were any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAEs were the AEs that developed or worsened or became serious after the administration of first dose of study drug in each period.

Pharmacokinetics (PK): Plasma Concentration of Rilzabrutinib

Data for this OM was not planned to be collected and analyzed for placebo arm of the study.

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

Anti-dsg1 and anti-dsg3 autoantibody levels was assessed by enzyme-linked immunosorbent assay (ELISA) method.

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

Anti-dsg1 and anti-dsg3 autoantibody levels was assessed by ELISA method.

Full Information

NCT ID

NCT03762265

First Posted

November 29, 2018

Last Updated

July 21, 2023

Sponsor

Principia Biopharma, a Sanofi Company

1. Study Identification

Unique Protocol Identification Number

NCT03762265

Brief Title

A Study of PRN1008 in Patients With Pemphigus

Official 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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Terminated

Why Stopped

Sponsor decision based on lack of efficacy

Study Start Date

January 8, 2019 (Actual)

Primary Completion Date

July 30, 2021 (Actual)

Study Completion Date

December 17, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Principia Biopharma, a Sanofi Company

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

This was a Phase 3 randomized, parallel-group, double-blind, placebo-controlled trial (blinded treatment [BT] period) followed by an open-label extension [OLE] period intended to evaluate the efficacy and safety of oral PRN1008 in moderate to severe pemphigus. After completing the open-label extension period, eligible participants might continue in a long term extension (LTE) Period of 48 weeks.

Detailed Description

A total of 131 male or female participants with newly diagnosed or relapsing moderate to severe pemphigus (pemphigus vulgaris [PV] or pemphigus foliaceus [PF]) were enrolled in the trial worldwide. The trial would last 68 weeks (approximately 17 months) for each participant. For participants eligible to enroll in the LTE, the trial might last up to 116 weeks. Participants were randomized at Day 1, using a 1:1 ratio to receive PRN1008 or placebo twice per day, by relapsing/newly diagnosed disease history (newly diagnosed defined as within 6 months of screening).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pemphigus

Keywords

Pemphigus Vulgaris (PV), Pemphigus Foliaceus (PF)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

131 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo Then Rilzabrutinib

Arm Type

Placebo Comparator

Arm Description

Arm Title

Rilzabrutinib Then Rilzabrutinib

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Rilzabrutinib

Intervention Description

Pharmaceutical form: Tablet Route of administration: Oral

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Pharmaceutical form: Tablet Route of administration: Oral

Primary Outcome Measure Information:

Title

Description

Time Frame

From Week 29 to Week 37

Title

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

Description

Time Frame

From Week 29 to Week 37

Secondary Outcome Measure Information:

Title

Cumulative Oral Corticosteroid Dose From Baseline to Week 37: PV mITT Population

Description

Time Frame

Baseline to Week 37

Title

Cumulative Oral Corticosteroid Dose From Baseline to Week 37: mITT Population

Description

Time Frame

Baseline to Week 37

Title

Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: PV mITT Population

Description

Time Frame

Baseline to Week 37

Title

Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: mITT Population

Description

Time Frame

Baseline to Week 37

Title

Time to First Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: PV mITT Population

Description

Time Frame

Baseline to Week 37

Title

Time to First Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: mITT Population

Description

Time Frame

Baseline to Week 37

Title

Percentage of Participants Who Achieved Complete Remission With a Corticosteroids Dose of <=5 mg/Day From Week 29 to Week 37: PV mITT Population

Description

Time Frame

From Week 29 to Week 37

Title

Percentage of Participants Who Achieved Complete Remission With a Corticosteroids Dose of <=5 mg/Day From Week 29 to Week 37: mITT Population

Description

Time Frame

From Week 29 to Week 37

Title

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

Description

Time Frame

From Week 29 to Week 37

Title

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

Description

Time Frame

From Week 29 to Week 37

Title

Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Weeks 61 and 109: PV mITT Population

Description

Time Frame

Baseline to Week 61 and Baseline to Week 109

Title

Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Weeks 61 and 109: mITT Population

Description

Time Frame

Baseline to Weeks 61 and Baseline to Week 109

Title

Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Baseline to Weeks 61 and 109: PV mITT Population

Description

Time Frame

Baseline to Week 61 and Baseline to Week 109

Title

Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Baseline to Weeks 61 and 109: mITT Population

Description

Time Frame

Baseline to Week 61 and Baseline to Week 109

Title

Glucocorticoid Toxicity Index (GTI) - Cumulative Worsening Score (CWS) and Aggregate Improvement Score (AIS) at Week 37: PV mITT Population

Description

Time Frame

At Week 37

Title

Glucocorticoid Toxicity Index - Cumulative Worsening Score and Aggregate Improvement Score at Week 37: mITT Population

Description

Time Frame

At Week 37

Title

Change From Baseline in Pemphigus Disease Area Index Score at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population

Description

PDAI is specific cutaneous and mucosal disease activity assessment performed by investigator based on evaluation of lesions in well-defined anatomical locations. The score weighted for the number and size of lesions with score of 0 (absent) to 10 given for skin (12 body locations), scalp and mucous membrane showing disease activity (erosions/blisters or new erythema). Thus, PDAI total activity score ranged from 0 to 250 points representing disease activity (120 points for skin activity; 10 points for scalp activity; 120 points for mucosal activity). Higher score indicated more disease activity. PDAI activity score was measured independently of the CS dose administered in the participants.

Time Frame

Baseline, Weeks 5, 13, 25, 37, 61, and 109

Title

Change From Baseline in Pemphigus Disease Area Index Score at Weeks 5, 13, 25, 37, 61, and 109: mITT Population

Description

PDAI is specific cutaneous and mucosal disease activity assessment performed by investigator based on evaluation of lesions in well-defined anatomical locations. The score weighted for the number and size of lesions with score of 0 (absent) to 10 given for skin (12 body locations), scalp and mucous membrane showing disease activity (erosions/blisters or new erythema). Thus, PDAI total activity score ranged from 0 to 250 points representing disease activity (120 points for skin activity; 10 points for scalp activity; 120 points for mucosal activity). Higher score indicated more disease activity. PDAI activity score was measured independently of the CS dose administered in the participants.

Time Frame

Baseline, Weeks 5, 13, 25, 37, 61, and 109

Title

Change From Baseline in Autoimmune Bullous Disease Quality of Life (ABQOL) Score at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population

Description

Time Frame

Baseline, Weeks 5, 13, 25, 37, 61, and 109

Title

Change From Baseline in Autoimmune Bullous Disease Quality of Life Score at Weeks 5, 13, 25, 37, 61, and 109: mITT Population

Description

Time Frame

Baseline, Weeks 5, 13, 25, 37, 61, and 109

Title

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

Description

Time Frame

At Weeks 5, 13, 25, 37, 61, and 109

Title

Percentage of Participants With Autoimmune Bullous Disease Quality of Life Score of Zero at Weeks 5, 13, 25, 37, 61, and 109: mITT Population

Description

Time Frame

At Weeks 5, 13, 25, 37, 61, and 109

Title

Description

Time Frame

Baseline, Weeks 5, 13, 25, 37, 61, and 109

Title

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

Description

Time Frame

Baseline, Weeks 5, 13, 25, 37, 61, and 109

Title

Time to First Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Weeks 61 and 109

Description

Time Frame

Baseline to Week 61 and Baseline to Week 109

Title

Total Number of Disease Relapses/Flares From Initial Control of Disease Activity (CDA) to Week 37: PV mITT Population

Description

Time Frame

From initial CDA up to Week 37 (i.e., during any time from Baseline up to Week 37)

Title

Total Number of Disease Relapses/Flares From Initial Control of Disease Activity to Week 37: mITT Population

Description

Time Frame

From initial CDA up to Week 37 (i.e., during any time from Baseline up to Week 37)

Title

Time to Initial Relapse/Flare From Initial Control of Disease Activity to Week 37: PV mITT Population

Description

Time Frame

From initial CDA up to Week 37 (i.e., during any time from Baseline up to Week 37)

Title

Time to Initial Relapse/Flare From Initial Control of Disease Activity to Week 37: mITT Population

Description

Time Frame

From initial CDA up to Week 37 (i.e., during any time from Baseline up to Week 37)

Title

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

Description

Time Frame

At Week 37

Title

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

Description

Time Frame

At Week 37

Title

Percentage of Participants With at Least One Disease Relapse/Flare From Initial Control of Disease Activity to Week 37: PV mITT Population

Description

Time Frame

From initial CDA up to Week 37 (i.e., during any time from Baseline up to Week 37)

Title

Percentage of Participants With at Least One Disease Relapse/Flare From Initial Control of Disease Activity to Week 37: mITT Population

Description

Time Frame

From initial CDA up to Week 37 (i.e., during any time from Baseline up to Week 37)

Title

Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Week 37 to Week 61: PV mITT Population

Description

Time Frame

From Week 37 to Week 61

Title

Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Week 37 to Week 61: mITT Population

Description

Time Frame

From Week 37 to Week 61

Title

Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Week 37 to Week 61: PV mITT Population

Description

Time Frame

From Week 37 to Week 61

Title

Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Week 37 to Week 61: mITT Population

Description

Time Frame

From Week 37 to Week 61

Title

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

Description

Time Frame

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)

Title

Pharmacokinetics (PK): Plasma Concentration of Rilzabrutinib

Description

Data for this OM was not planned to be collected and analyzed for placebo arm of the study.

Time Frame

Pre-dose and 2 hours post-dose on Day 1

Title

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

Description

Anti-dsg1 and anti-dsg3 autoantibody levels was assessed by enzyme-linked immunosorbent assay (ELISA) method.

Time Frame

Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, and 109

Title

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

Description

Anti-dsg1 and anti-dsg3 autoantibody levels was assessed by ELISA method.

Time Frame

Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, and 109

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

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. 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.

Facility Information:

Facility Name

Central Recruiting (Principia Biopharma)

City

Boca Raton

State/Province

Florida

ZIP/Postal Code

33433

Country

United States

Facility Name

Central Recruiting (Principia Biopharma)

City

Coral Gables

State/Province

Florida

ZIP/Postal Code

33134

Country

United States

Facility Name

Central Recruiting (Principia Biopharma)

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30322

Country

United States

Facility Name

Central Recruiting (Principia Biopharma)

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48103

Country

United States

Facility Name

Central Recruiting (Principia Biopharma)

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48109

Country

United States

Facility Name

Central Recruiting (Principia Biopharma)

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

Facility Name

Central Recruiting (Principia Biopharma)

City

Albuquerque

State/Province

New Mexico

ZIP/Postal Code

87131

Country

United States

Facility Name

Central Recruiting (Principia Biopharma)

City

New York

State/Province

New York

ZIP/Postal Code

10016

Country

United States

Facility Name

Central Recruiting (Principia Biopharma)

City

New York

State/Province

New York

ZIP/Postal Code

10028

Country

United States

Facility Name

Central Recruiting (Principia Biopharma)

City

Chapel Hill

State/Province

North Carolina

ZIP/Postal Code

27599

Country

United States

Facility Name

Central Recruiting (Principia Biopharma)

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27710

Country

United States

Facility Name

Central Recruiting (Principia Biopharma)

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44106

Country

United States

Facility Name

Central Recruiting (Principia Biopharma)

City

Austin

State/Province

Texas

ZIP/Postal Code

78705

Country

United States

Facility Name

Central Recruiting (Principia Biopharma)

City

Murray

State/Province

Utah

ZIP/Postal Code

84107

Country

United States

Facility Name

Central Recruiting (Principia Biopharma)

City

Buenos Aires

ZIP/Postal Code

B1663GJR

Country

Argentina

Facility Name

Central Recruiting (Principia Biopharma)

City

Buenos Aires

ZIP/Postal Code

C1199ABD

Country

Argentina

Facility Name

Central Recruiting (Principia Biopharma)

City

San Nicolás

ZIP/Postal Code

B2900DPA

Country

Argentina

Facility Name

Central Recruiting (Principia Biopharma)

City

Fremantle

State/Province

Western Australia

ZIP/Postal Code

6160

Country

Australia

Facility Name

Central Recruiting (Principia Biopharma)

City

Melbourne

ZIP/Postal Code

3050

Country

Australia

Facility Name

Central Recruiting (Principia Biopharma)

City

Sydney

ZIP/Postal Code

2217

Country

Australia

Facility Name

Central Recruiting (Principia Biopharma)

City

Campinas

ZIP/Postal Code

87131-001

Country

Brazil

Facility Name

Central Recruiting (Principia Biopharma)

City

Campo Grande

ZIP/Postal Code

79080-190

Country

Brazil

Facility Name

Central Recruiting (Principia Biopharma)

City

Ribeirão Preto

ZIP/Postal Code

14051-140

Country

Brazil

Facility Name

Central Recruiting (Principia Biopharma)

City

Pleven

ZIP/Postal Code

5800

Country

Bulgaria

Facility Name

Central Recruiting (Principia Biopharma)

City

Plovdiv

ZIP/Postal Code

4002

Country

Bulgaria

Facility Name

Central Recruiting (Principia Biopharma)

City

Sofia

ZIP/Postal Code

01431

Country

Bulgaria

Facility Name

Central Recruiting (Principia Biopharma)

City

Winnipeg

State/Province

Manitoba

ZIP/Postal Code

R3M 3Z4

Country

Canada

Facility Name

Central Recruiting (Principia Biopharma)

City

Osijek

ZIP/Postal Code

31000

Country

Croatia

Facility Name

Central Recruiting (Principia Biopharma)

City

Zagreb

ZIP/Postal Code

10000

Country

Croatia

Facility Name

Central Recruiting (Principia Biopharma)

City

Bobigny

ZIP/Postal Code

93009

Country

France

Facility Name

Central Recruiting (Principia Biopharma)

City

Bordeaux

ZIP/Postal Code

33000

Country

France

Facility Name

Central Recruiting (Principia Biopharma)

City

Lille

ZIP/Postal Code

59037

Country

France

Facility Name

Central Recruiting (Principia Biopharma)

City

Pierre-Bénite

ZIP/Postal Code

69495

Country

France

Facility Name

Central Recruiting (Principia Biopharma)

City

Rouen

ZIP/Postal Code

76031

Country

France

Facility Name

Central Recruiting (Principia Biopharma)

City

Toulouse

ZIP/Postal Code

31059

Country

France

Facility Name

Central Recruiting (Principia Biopharma)

City

Berlin

ZIP/Postal Code

10117

Country

Germany

Facility Name

Central Recruiting (Principia Biopharma)

City

Dresden

ZIP/Postal Code

01307

Country

Germany

Facility Name

Central Recruiting (Principia Biopharma)

City

Düsseldorf

ZIP/Postal Code

40225

Country

Germany

Facility Name

Central Recruiting (Principia Biopharma)

City

Erlangen

ZIP/Postal Code

91054

Country

Germany

Facility Name

Central Recruiting (Principia Biopharma)

City

Heidelberg

ZIP/Postal Code

69120

Country

Germany

Facility Name

Central Recruiting (Principia Biopharma)

City

Kiel

ZIP/Postal Code

24105

Country

Germany

Facility Name

Central Recruiting (Principia Biopharma)

City

Lübeck

ZIP/Postal Code

23538

Country

Germany

Facility Name

Central Recruiting (Principia Biopharma)

City

Münster

ZIP/Postal Code

48151

Country

Germany

Facility Name

Central Recruiting (Principia Biopharma)

City

Athens

ZIP/Postal Code

16121

Country

Greece

Facility Name

Central Recruiting (Principia Biopharma)

City

Ioánnina

ZIP/Postal Code

54643

Country

Greece

Facility Name

Central Recruiting (Principia Biopharma)

City

Larisa

ZIP/Postal Code

41110

Country

Greece

Facility Name

Central Recruiting (Principia Biopharma)

City

Thessaloníki

ZIP/Postal Code

54643

Country

Greece

Facility Name

Central Recruiting (Principia Biopharma)

City

Thessaloníki

ZIP/Postal Code

56403

Country

Greece

Facility Name

Central Recruiting (Principia Biopharma)

City

Be'er Sheva

ZIP/Postal Code

8457108

Country

Israel

Facility Name

Central Recruiting (Principia Biopharma)

City

Haifa

ZIP/Postal Code

3109601

Country

Israel

Facility Name

Central Recruiting (Principia Biopharma)

City

Ramat Gan

ZIP/Postal Code

5262100

Country

Israel

Facility Name

Central Recruiting (Principia Biopharma)

City

Tel Aviv

ZIP/Postal Code

64239

Country

Israel

Facility Name

Central Recruiting (Principia Biopharma)

City

Brescia

ZIP/Postal Code

25123

Country

Italy

Facility Name

Central Recruiting (Principia Biopharma)

City

Catania

ZIP/Postal Code

95123

Country

Italy

Facility Name

Central Recruiting (Principia Biopharma)

City

Florence

ZIP/Postal Code

50121

Country

Italy

Facility Name

Central Recruiting (Principia Biopharma)

City

Milan

ZIP/Postal Code

20122

Country

Italy

Facility Name

Central Recruiting (Principia Biopharma)

City

Padova

ZIP/Postal Code

35128

Country

Italy

Facility Name

Central Recruiting (Principia Biopharma)

City

Parma

ZIP/Postal Code

43100

Country

Italy

Facility Name

Central Recruiting (Principia Biopharma)

City

Rome

ZIP/Postal Code

00167

Country

Italy

Facility Name

Central Recruiting (Principia Biopharma)

City

Torino

ZIP/Postal Code

43100

Country

Italy

Facility Name

Central Recruiting (Principia Biopharma)

City

Gdańsk

ZIP/Postal Code

80-214

Country

Poland

Facility Name

Central Recruiting (Principia Biopharma)

City

Kraków

ZIP/Postal Code

31-066

Country

Poland

Facility Name

Central Recruiting (Principia Biopharma)

City

Lublin

ZIP/Postal Code

20-081

Country

Poland

Facility Name

Central Recruiting (Principia Biopharma)

City

Warsaw

ZIP/Postal Code

02-005

Country

Poland

Facility Name

Central Recruiting (Principia Biopharma)

City

Wroclaw

ZIP/Postal Code

51-124

Country

Poland

Facility Name

Central Recruiting (Principia Biopharma)

City

Wrocław

ZIP/Postal Code

50-367

Country

Poland

Facility Name

Central Recruiting (Principia Biopharma)

City

Belgrade

ZIP/Postal Code

11000

Country

Serbia

Facility Name

Central Recruiting (Principia Biopharma)

City

Novi Sad

ZIP/Postal Code

21000

Country

Serbia

Facility Name

Central Recruiting (Principia Biopharma)

City

Barcelona

ZIP/Postal Code

08003

Country

Spain

Facility Name

Central Recruiting (Principia Biopharma)

City

Barcelona

ZIP/Postal Code

08036

Country

Spain

Facility Name

Central Recruiting (Principia Biopharma)

City

Barcelona

ZIP/Postal Code

08916

Country

Spain

Facility Name

Central Recruiting (Principia Biopharma)

City

Córdoba

ZIP/Postal Code

14004

Country

Spain

Facility Name

Central Recruiting (Principia Biopharma)

City

Madrid

ZIP/Postal Code

28007

Country

Spain

Facility Name

Central Recruiting (Principia Biopharma)

City

Pamplona

ZIP/Postal Code

31008

Country

Spain

Facility Name

Central Recruiting (Principia Biopharma)

City

Dalin

ZIP/Postal Code

62247

Country

Taiwan

Facility Name

Central Recruiting (Principia Biopharma)

City

Kaohsiung

ZIP/Postal Code

83301

Country

Taiwan

Facility Name

Central Recruiting (Principia Biopharma)

City

Taipei

ZIP/Postal Code

100

Country

Taiwan

Facility Name

Central Recruiting (Principia Biopharma)

City

Fatih

ZIP/Postal Code

34093

Country

Turkey

Facility Name

Central Recruiting (Principia Biopharma)

City

Istanbul

ZIP/Postal Code

34662

Country

Turkey

Facility Name

Central Recruiting (Principia Biopharma)

City

Istanbul

ZIP/Postal Code

34722

Country

Turkey

Facility Name

Central Recruiting (Principia Biopharma)

City

Konyaaltı

ZIP/Postal Code

07070

Country

Turkey

Facility Name

Central Recruiting (Principia Biopharma)

City

Merkez

ZIP/Postal Code

61080

Country

Turkey

Facility Name

Central Recruiting (Principia Biopharma)

City

Dnipro

ZIP/Postal Code

49000

Country

Ukraine

Facility Name

Central Recruiting (Principia Biopharma)

City

Dnipro

ZIP/Postal Code

49074

Country

Ukraine

Facility Name

Central Recruiting (Principia Biopharma)

City

Kyiv

ZIP/Postal Code

04209

Country

Ukraine

Facility Name

Central Recruiting (Principia Biopharma)

City

Lviv

ZIP/Postal Code

79013

Country

Ukraine

Facility Name

Central Recruiting (Principia Biopharma)

City

Zaporizhzhya

ZIP/Postal Code

69063

Country

Ukraine

Facility Name

Central Recruiting (Principia Biopharma)

City

London

ZIP/Postal Code

E1 1BB

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

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

Learn more about this trial

A Study of PRN1008 in Patients With Pemphigus

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A Study of PRN1008 in Patients With Pemphigus

Pemphigus

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial