A Study of PRN1008 in Patients With Pemphigus

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

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.

Study Overview

• Status: Terminated
• Conditions: Pemphigus
• Intervention / Treatment: Drug: Rilzabrutinib; Drug: Placebo

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).

• Study Type: Interventional
• Enrollment (Actual): 131
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, B1663GJR
    • Central Recruiting (Principia Biopharma)
  • Buenos Aires, Argentina, C1199ABD
    • Central Recruiting (Principia Biopharma)
  • San Nicolás, Argentina, B2900DPA
    • Central Recruiting (Principia Biopharma)
• Australia
  • Melbourne, Australia, 3050
    • Central Recruiting (Principia Biopharma)
  • Sydney, Australia, 2217
    • Central Recruiting (Principia Biopharma)
  • Western Australia
    • Fremantle, Western Australia, Australia, 6160
      • Central Recruiting (Principia Biopharma)
• Brazil
  • Campinas, Brazil, 87131-001
    • Central Recruiting (Principia Biopharma)
  • Campo Grande, Brazil, 79080-190
    • Central Recruiting (Principia Biopharma)
  • Ribeirão Preto, Brazil, 14051-140
    • Central Recruiting (Principia Biopharma)
• Bulgaria
  • Pleven, Bulgaria, 5800
    • Central Recruiting (Principia Biopharma)
  • Plovdiv, Bulgaria, 4002
    • Central Recruiting (Principia Biopharma)
  • Sofia, Bulgaria, 01431
    • Central Recruiting (Principia Biopharma)
• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3M 3Z4
      • Central Recruiting (Principia Biopharma)
• Croatia
  • Osijek, Croatia, 31000
    • Central Recruiting (Principia Biopharma)
  • Zagreb, Croatia, 10000
    • Central Recruiting (Principia Biopharma)
• France
  • Bobigny, France, 93009
    • Central Recruiting (Principia Biopharma)
  • Bordeaux, France, 33000
    • Central Recruiting (Principia Biopharma)
  • Lille, France, 59037
    • Central Recruiting (Principia Biopharma)
  • Pierre-Bénite, France, 69495
    • Central Recruiting (Principia Biopharma)
  • Rouen, France, 76031
    • Central Recruiting (Principia Biopharma)
  • Toulouse, France, 31059
    • Central Recruiting (Principia Biopharma)
• Germany
  • Berlin, Germany, 10117
    • Central Recruiting (Principia Biopharma)
  • Dresden, Germany, 01307
    • Central Recruiting (Principia Biopharma)
  • Düsseldorf, Germany, 40225
    • Central Recruiting (Principia Biopharma)
  • Erlangen, Germany, 91054
    • Central Recruiting (Principia Biopharma)
  • Heidelberg, Germany, 69120
    • Central Recruiting (Principia Biopharma)
  • Kiel, Germany, 24105
    • Central Recruiting (Principia Biopharma)
  • Lübeck, Germany, 23538
    • Central Recruiting (Principia Biopharma)
  • Münster, Germany, 48151
    • Central Recruiting (Principia Biopharma)
• Greece
  • Athens, Greece, 16121
    • Central Recruiting (Principia Biopharma)
  • Ioánnina, Greece, 54643
    • Central Recruiting (Principia Biopharma)
  • Larisa, Greece, 41110
    • Central Recruiting (Principia Biopharma)
  • Thessaloníki, Greece, 54643
    • Central Recruiting (Principia Biopharma)
  • Thessaloníki, Greece, 56403
    • Central Recruiting (Principia Biopharma)
• Israel
  • Be'er Sheva, Israel, 8457108
    • Central Recruiting (Principia Biopharma)
  • Haifa, Israel, 3109601
    • Central Recruiting (Principia Biopharma)
  • Ramat Gan, Israel, 5262100
    • Central Recruiting (Principia Biopharma)
  • Tel Aviv, Israel, 64239
    • Central Recruiting (Principia Biopharma)
• Italy
  • Brescia, Italy, 25123
    • Central Recruiting (Principia Biopharma)
  • Catania, Italy, 95123
    • Central Recruiting (Principia Biopharma)
  • Florence, Italy, 50121
    • Central Recruiting (Principia Biopharma)
  • Milan, Italy, 20122
    • Central Recruiting (Principia Biopharma)
  • Padova, Italy, 35128
    • Central Recruiting (Principia Biopharma)
  • Parma, Italy, 43100
    • Central Recruiting (Principia Biopharma)
  • Rome, Italy, 00167
    • Central Recruiting (Principia Biopharma)
  • Torino, Italy, 43100
    • Central Recruiting (Principia Biopharma)
• Poland
  • Gdańsk, Poland, 80-214
    • Central Recruiting (Principia Biopharma)
  • Kraków, Poland, 31-066
    • Central Recruiting (Principia Biopharma)
  • Lublin, Poland, 20-081
    • Central Recruiting (Principia Biopharma)
  • Warsaw, Poland, 02-005
    • Central Recruiting (Principia Biopharma)
  • Wroclaw, Poland, 51-124
    • Central Recruiting (Principia Biopharma)
  • Wrocław, Poland, 50-367
    • Central Recruiting (Principia Biopharma)
• Serbia
  • Belgrade, Serbia, 11000
    • Central Recruiting (Principia Biopharma)
  • Novi Sad, Serbia, 21000
    • Central Recruiting (Principia Biopharma)
• Spain
  • Barcelona, Spain, 08003
    • Central Recruiting (Principia Biopharma)
  • Barcelona, Spain, 08036
    • Central Recruiting (Principia Biopharma)
  • Barcelona, Spain, 08916
    • Central Recruiting (Principia Biopharma)
  • Córdoba, Spain, 14004
    • Central Recruiting (Principia Biopharma)
  • Madrid, Spain, 28007
    • Central Recruiting (Principia Biopharma)
  • Pamplona, Spain, 31008
    • Central Recruiting (Principia Biopharma)
• Taiwan
  • Dalin, Taiwan, 62247
    • Central Recruiting (Principia Biopharma)
  • Kaohsiung, Taiwan, 83301
    • Central Recruiting (Principia Biopharma)
  • Taipei, Taiwan, 100
    • Central Recruiting (Principia Biopharma)
• Turkey
  • Fatih, Turkey, 34093
    • Central Recruiting (Principia Biopharma)
  • Istanbul, Turkey, 34662
    • Central Recruiting (Principia Biopharma)
  • Istanbul, Turkey, 34722
    • Central Recruiting (Principia Biopharma)
  • Konyaaltı, Turkey, 07070
    • Central Recruiting (Principia Biopharma)
  • Merkez, Turkey, 61080
    • Central Recruiting (Principia Biopharma)
• Ukraine
  • Dnipro, Ukraine, 49000
    • Central Recruiting (Principia Biopharma)
  • Dnipro, Ukraine, 49074
    • Central Recruiting (Principia Biopharma)
  • Kyiv, Ukraine, 04209
    • Central Recruiting (Principia Biopharma)
  • Lviv, Ukraine, 79013
    • Central Recruiting (Principia Biopharma)
  • Zaporizhzhya, Ukraine, 69063
    • Central Recruiting (Principia Biopharma)
• United Kingdom
  • London, United Kingdom, E1 1BB
    • Central Recruiting (Principia Biopharma)
• United States
  • Florida
    • Boca Raton, Florida, United States, 33433
      • Central Recruiting (Principia Biopharma)
    • Coral Gables, Florida, United States, 33134
      • Central Recruiting (Principia Biopharma)
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Central Recruiting (Principia Biopharma)
  • Michigan
    • Ann Arbor, Michigan, United States, 48103
      • Central Recruiting (Principia Biopharma)
    • Ann Arbor, Michigan, United States, 48109
      • Central Recruiting (Principia Biopharma)
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Central Recruiting (Principia Biopharma)
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • Central Recruiting (Principia Biopharma)
  • New York
    • New York, New York, United States, 10016
      • Central Recruiting (Principia Biopharma)
    • New York, New York, United States, 10028
      • Central Recruiting (Principia Biopharma)
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Central Recruiting (Principia Biopharma)
    • Durham, North Carolina, United States, 27710
      • Central Recruiting (Principia Biopharma)
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Central Recruiting (Principia Biopharma)
  • Texas
    • Austin, Texas, United States, 78705
      • Central Recruiting (Principia Biopharma)
  • Utah
    • Murray, Utah, United States, 84107
      • Central Recruiting (Principia Biopharma)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From Week 29 to Week 37
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.	From Week 29 to Week 37

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline to Week 37
Cumulative Oral Corticosteroid Dose From Baseline to Week 37: 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.	Baseline to Week 37
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".	Baseline to Week 37
Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: 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".	Baseline to Week 37
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.	Baseline to Week 37
Time to First Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: 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.	Baseline to Week 37
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.	From Week 29 to Week 37
Percentage of Participants Who Achieved Complete Remission With a Corticosteroids Dose of <=5 mg/Day From Week 29 to Week 37: 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.	From Week 29 to Week 37
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.	From Week 29 to Week 37
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	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.	From Week 29 to Week 37
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".	Baseline to Week 61 and Baseline to Week 109
Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Weeks 61 and 109: 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".	Baseline to Weeks 61 and Baseline to Week 109
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".	Baseline to Week 61 and Baseline to Week 109
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".	Baseline to Week 61 and Baseline to Week 109
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.	At Week 37
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.	At Week 37
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.	Baseline, Weeks 5, 13, 25, 37, 61, and 109
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.	Baseline, Weeks 5, 13, 25, 37, 61, and 109
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.	Baseline, Weeks 5, 13, 25, 37, 61, and 109
Change From Baseline in Autoimmune Bullous Disease Quality of Life Score at Weeks 5, 13, 25, 37, 61, and 109: 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.	Baseline, Weeks 5, 13, 25, 37, 61, and 109
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	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.	At Weeks 5, 13, 25, 37, 61, and 109
Percentage of Participants With Autoimmune Bullous Disease Quality of Life Score of Zero at Weeks 5, 13, 25, 37, 61, and 109: 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. Percentage of participants with ABQOL score of '0' were reported in this outcome measure.	At Weeks 5, 13, 25, 37, 61, and 109
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.	Baseline, Weeks 5, 13, 25, 37, 61, and 109
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.	Baseline, Weeks 5, 13, 25, 37, 61, and 109
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".	Baseline to Week 61 and Baseline to Week 109
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.	From initial CDA up to Week 37 (i.e., during any time from Baseline up to Week 37)
Total Number of Disease Relapses/Flares From Initial Control of Disease Activity to Week 37: 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.	From initial CDA up to Week 37 (i.e., during any time from Baseline up to Week 37)
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.	From initial CDA up to Week 37 (i.e., during any time from Baseline up to Week 37)
Time to Initial Relapse/Flare From Initial Control of Disease Activity to Week 37: 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.	From initial CDA up to Week 37 (i.e., during any time from Baseline up to Week 37)
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.	At Week 37
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.	At Week 37
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.	From initial CDA up to Week 37 (i.e., during any time from Baseline up to Week 37)
Percentage of Participants With at Least One Disease Relapse/Flare From Initial Control of Disease Activity to Week 37: 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.	From initial CDA up to Week 37 (i.e., during any time from Baseline up to Week 37)
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".	From Week 37 to Week 61
Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Week 37 to Week 61: 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".	From Week 37 to Week 61
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".	From Week 37 to Week 61
Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Week 37 to Week 61: 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".	From Week 37 to Week 61
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.	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)
Pharmacokinetics (PK): Plasma Concentration of Rilzabrutinib	Data for this OM was not planned to be collected and analyzed for placebo arm of the study.	Pre-dose and 2 hours post-dose on Day 1
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.	Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, and 109
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.	Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, and 109

Collaborators and Investigators

• Sponsor: Principia Biopharma, a Sanofi Company

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2019
• Primary Completion (Actual): July 30, 2021
• Study Completion (Actual): December 17, 2021

Study Registration Dates

• First Submitted: November 29, 2018
• First Submitted That Met QC Criteria: November 30, 2018
• First Posted (Actual): December 3, 2018

Study Record Updates

• Last Update Posted (Actual): August 2, 2023
• Last Update Submitted That Met QC Criteria: July 21, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Pemphigus Vulgaris (PV); Pemphigus Foliaceus (PF)
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Autoimmune Diseases; Skin Diseases, Vesiculobullous; Pemphigus
• Other Study ID Numbers: EFC17092; PRN1008-012 (Other Identifier: Principia Biopharma); 2018-002261-19 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No