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A Study of PRN1008 in Patients With Pemphigus

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03762265
Recruitment Status : Terminated (Sponsor decision based on lack of efficacy)
First Posted : December 3, 2018
Results First Posted : September 21, 2022
Last Update Posted : September 21, 2022
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Principia Biopharma, a Sanofi Company )

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.

Condition or disease Intervention/treatment Phase
Pemphigus Drug: Rilzabrutinib Drug: Placebo Phase 3

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).

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 131 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : January 8, 2019
Actual Primary Completion Date : July 30, 2021
Actual Study Completion Date : December 17, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pemphigus Steroids

Arm Intervention/treatment
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.
Drug: Rilzabrutinib
Pharmaceutical form: Tablet Route of administration: Oral

Drug: Placebo
Pharmaceutical form: Tablet Route of administration: Oral

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.
Drug: Rilzabrutinib
Pharmaceutical form: Tablet Route of administration: Oral




Primary Outcome Measures :
  1. 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 [ Time Frame: From Week 29 to Week 37 ]
    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.

  2. 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 [ Time Frame: From Week 29 to Week 37 ]
    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 :
  1. Cumulative Oral Corticosteroid Dose From Baseline to Week 37: PV mITT Population [ Time Frame: Baseline to Week 37 ]
    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.

  2. Cumulative Oral Corticosteroid Dose From Baseline to Week 37: mITT Population [ Time Frame: Baseline to Week 37 ]
    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.

  3. Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: PV mITT Population [ Time Frame: Baseline to Week 37 ]
    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".

  4. Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: mITT Population [ Time Frame: Baseline to Week 37 ]
    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".

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

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

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

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

  9. 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 [ Time Frame: From Week 29 to Week 37 ]
    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.

  10. 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 [ Time Frame: From Week 29 to Week 37 ]
    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.

  11. Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Weeks 61 and 109: PV mITT Population [ Time Frame: Baseline to Week 61 and Baseline to Week 109 ]
    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".

  12. Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Weeks 61 and 109: mITT Population [ Time Frame: Baseline to Weeks 61 and Baseline to Week 109 ]
    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".

  13. Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Baseline to Weeks 61 and 109: PV mITT Population [ Time Frame: Baseline to Week 61 and Baseline to Week 109 ]
    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".

  14. Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Baseline to Weeks 61 and 109: mITT Population [ Time Frame: Baseline to Week 61 and Baseline to Week 109 ]
    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".

  15. Glucocorticoid Toxicity Index (GTI) - Cumulative Worsening Score (CWS) and Aggregate Improvement Score (AIS) at Week 37: PV mITT Population [ Time Frame: At Week 37 ]
    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.

  16. Glucocorticoid Toxicity Index - Cumulative Worsening Score and Aggregate Improvement Score at Week 37: mITT Population [ Time Frame: At Week 37 ]
    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.

  17. Change From Baseline in Pemphigus Disease Area Index Score at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population [ Time Frame: Baseline, Weeks 5, 13, 25, 37, 61, and 109 ]
    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.

  18. Change From Baseline in Pemphigus Disease Area Index Score at Weeks 5, 13, 25, 37, 61, and 109: mITT Population [ Time Frame: Baseline, Weeks 5, 13, 25, 37, 61, and 109 ]
    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.

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

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

  21. 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 [ Time Frame: At Weeks 5, 13, 25, 37, 61, and 109 ]
    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. Percentage of participants with ABQOL score of '0' were reported in this outcome measure.

  22. Percentage of Participants With Autoimmune Bullous Disease Quality of Life Score of Zero at Weeks 5, 13, 25, 37, 61, and 109: mITT Population [ Time Frame: At Weeks 5, 13, 25, 37, 61, and 109 ]
    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. Percentage of participants with ABQOL score of '0' were reported in this outcome measure.

  23. 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 [ Time Frame: Baseline, 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.

  24. 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 [ Time Frame: Baseline, 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.

  25. Time to First Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Weeks 61 and 109 [ Time Frame: Baseline to Week 61 and Baseline to Week 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".

  26. Total Number of Disease Relapses/Flares From Initial Control of Disease Activity (CDA) to Week 37: PV mITT Population [ Time Frame: From initial CDA up to Week 37 (i.e., during any time from Baseline up to Week 37) ]
    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.

  27. Total Number of Disease Relapses/Flares From Initial Control of Disease Activity to Week 37: mITT Population [ Time Frame: From initial CDA up to Week 37 (i.e., during any time from Baseline up to Week 37) ]
    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.

  28. Time to Initial Relapse/Flare From Initial Control of Disease Activity to Week 37: PV mITT Population [ Time Frame: From initial CDA up to Week 37 (i.e., during any time from Baseline up to Week 37) ]
    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.

  29. Time to Initial Relapse/Flare From Initial Control of Disease Activity to Week 37: mITT Population [ Time Frame: From initial CDA up to Week 37 (i.e., during any time from Baseline up to Week 37) ]
    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.

  30. 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 [ Time Frame: At Week 37 ]
    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.

  31. 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 [ Time Frame: At Week 37 ]
    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.

  32. Percentage of Participants With at Least One Disease Relapse/Flare From Initial Control of Disease Activity to Week 37: PV mITT Population [ Time Frame: From initial CDA up to Week 37 (i.e., during any time from Baseline up to Week 37) ]
    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.

  33. Percentage of Participants With at Least One Disease Relapse/Flare From Initial Control of Disease Activity to Week 37: mITT Population [ Time Frame: From initial CDA up to Week 37 (i.e., during any time from Baseline up to Week 37) ]
    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.

  34. Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Week 37 to Week 61: PV mITT Population [ Time Frame: From Week 37 to Week 61 ]
    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".

  35. Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Week 37 to Week 61: mITT Population [ Time Frame: From Week 37 to Week 61 ]
    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".

  36. Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Week 37 to Week 61: PV mITT Population [ Time Frame: From Week 37 to Week 61 ]
    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".

  37. Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Week 37 to Week 61: mITT Population [ Time Frame: From Week 37 to Week 61 ]
    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".

  38. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) [ 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) ]
    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.

  39. Pharmacokinetics (PK): Plasma Concentration of Rilzabrutinib [ Time Frame: Pre-dose and 2 hours post-dose on Day 1 ]
    Data for this OM was not planned to be collected and analyzed for placebo arm of the study.

  40. 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 [ Time Frame: Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, and 109 ]
    Anti-dsg1 and anti-dsg3 autoantibody levels was assessed by enzyme-linked immunosorbent assay (ELISA) method.

  41. 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 [ Time Frame: Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, and 109 ]
    Anti-dsg1 and anti-dsg3 autoantibody levels was assessed by ELISA method.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03762265


Locations
Show Show 88 study locations
Sponsors and Collaborators
Principia Biopharma, a Sanofi Company
  Study Documents (Full-Text)

Documents provided by Sanofi ( Principia Biopharma, a Sanofi Company ):
Study Protocol  [PDF] August 30, 2021
Statistical Analysis Plan  [PDF] August 29, 2021

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Responsible Party: Principia Biopharma, a Sanofi Company
ClinicalTrials.gov Identifier: NCT03762265    
Other Study ID Numbers: EFC17092
PRN1008-012 ( Other Identifier: Principia Biopharma )
2018-002261-19 ( EudraCT Number )
First Posted: December 3, 2018    Key Record Dates
Results First Posted: September 21, 2022
Last Update Posted: September 21, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sanofi ( Principia Biopharma, a Sanofi Company ):
Pemphigus Vulgaris (PV)
Pemphigus Foliaceus (PF)
Additional relevant MeSH terms:
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Pemphigus
Skin Diseases, Vesiculobullous
Skin Diseases
Autoimmune Diseases
Immune System Diseases