Pemphigus
Conditions
Keywords
Pemphigus Vulgaris (PV), Pemphigus Foliaceus (PF)
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).
Interventions
DRUGRilzabrutinib
Pharmaceutical form: Tablet Route of administration: Oral
DRUGPlacebo
Pharmaceutical form: Tablet Route of administration: Oral
Sponsors
Principia Biopharma, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: PV mITT Population | 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. |
| Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: mITT Population | 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. |
| Time to First Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: PV mITT Population | 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. |
| Time to First Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: mITT Population | 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. |
| Percentage of Participants Who Achieved Complete Remission With a Corticosteroids Dose of <=5 mg/Day From Week 29 to Week 37: PV mITT Population | 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. |
| Percentage of Participants Who Achieved Complete Remission With a Corticosteroids Dose of <=5 mg/Day From Week 29 to Week 37: mITT Population | 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. |
| 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 | 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. |
| 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 | 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. |
| Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Weeks 61 and 109: PV mITT Population | 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. |
| Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Weeks 61 and 109: mITT Population | 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. |
| Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Baseline to Weeks 61 and 109: PV mITT Population | 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. |
| Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Baseline to Weeks 61 and 109: mITT Population | 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. |
| Glucocorticoid Toxicity Index (GTI) - Cumulative Worsening Score (CWS) and Aggregate Improvement Score (AIS) at Week 37: PV mITT Population | 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. |
| Glucocorticoid Toxicity Index - Cumulative Worsening Score and Aggregate Improvement Score at Week 37: mITT Population | 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. |
| Change From Baseline in Pemphigus Disease Area Index Score at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population | 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. |
| Change From Baseline in Pemphigus Disease Area Index Score at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | 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. |
| Change From Baseline in Autoimmune Bullous Disease Quality of Life (ABQOL) Score at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population | 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. |
| Change From Baseline in Autoimmune Bullous Disease Quality of Life Score at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | 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. |
| 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 | 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. |
| Percentage of Participants With Autoimmune Bullous Disease Quality of Life Score of Zero at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | 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. |
| 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 | 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. |
| 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 | 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. |
| Time to First Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Weeks 61 and 109 | 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. |
| Total Number of Disease Relapses/Flares From Initial Control of Disease Activity (CDA) to Week 37: PV mITT Population | 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. |
| Total Number of Disease Relapses/Flares From Initial Control of Disease Activity to Week 37: mITT Population | 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. |
| Time to Initial Relapse/Flare From Initial Control of Disease Activity to Week 37: PV mITT Population | 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. |
| Time to Initial Relapse/Flare From Initial Control of Disease Activity to Week 37: mITT Population | 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. |
| 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 | 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. |
| 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 | 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. |
| Percentage of Participants With at Least One Disease Relapse/Flare From Initial Control of Disease Activity to Week 37: PV mITT Population | 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. |
| Percentage of Participants With at Least One Disease Relapse/Flare From Initial Control of Disease Activity to Week 37: mITT Population | 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. |
| Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Week 37 to Week 61: PV mITT Population | 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. |
| Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Week 37 to Week 61: mITT Population | 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. |
| Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Week 37 to Week 61: PV mITT Population | 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. |
| Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Week 37 to Week 61: mITT Population | 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. |
| Cumulative Oral Corticosteroid Dose From Baseline to Week 37: PV mITT Population | 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. |
| Pharmacokinetics (PK): Plasma Concentration of Rilzabrutinib | 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. |
| 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 | 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. |
| 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 | Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, and 109 | Anti-dsg1 and anti-dsg3 autoantibody levels was assessed by ELISA method. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | 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. |
| Cumulative Oral Corticosteroid Dose From Baseline to Week 37: mITT Population | 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. |
Countries
Argentina, Australia, Brazil, Bulgaria, Canada, Croatia, France, Germany, Greece, Israel, Italy, Poland, Serbia, Spain, Taiwan, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Recruitment details
Study was conducted at 88 active sites in 19 countries. A total of 210 participants were screened from 08 January 2019 to 23 October 2020, of whom 79 participants were screen failures, mainly due to not meeting inclusion criteria. A total of 131 participants were enrolled and randomized in the study, consisted of 3 parts: blinded treatment (BT) period (Baseline to Week 37), open-label extension (OLE) period (Week 37 to Week 61) and long term extension (LTE) Period (Week 61 to Week 109).
Pre-assignment details
Participants with moderate to severe pemphigus (pemphigus vulgaris \[PV\] and pemphigus foliaceus \[PF\]) were randomized (1:1 ratio) to receive either rilzabrutinib or placebo in BT period.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Then Rilzabrutinib In BT period, participants received placebo 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 Week109 in LTE period according to protocol-specified criteria. | 66 |
| 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 and those who were eligible after OLE period completion, continued the same treatment until Week 109 in LTE period according to protocol-specified criteria. | 65 |
| Total | 131 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| BT Period: Weeks 1 to 37 | Adverse Event | 7 | 2 |
| BT Period: Weeks 1 to 37 | Lack of Efficacy | 1 | 0 |
| BT Period: Weeks 1 to 37 | Other | 0 | 1 |
| BT Period: Weeks 1 to 37 | Physician Decision | 1 | 0 |
| BT Period: Weeks 1 to 37 | Required prohibited medication | 2 | 0 |
| BT Period: Weeks 1 to 37 | Withdrawal by Subject | 4 | 0 |
| LTE Period: Weeks 61 to 109 | Lack of Efficacy | 0 | 1 |
| LTE Period: Weeks 61 to 109 | Other | 1 | 0 |
| LTE Period: Weeks 61 to 109 | Study terminated by sponsor | 28 | 25 |
| LTE Period: Weeks 61 to 109 | Withdrawal by Subject | 0 | 2 |
| OLE Period: Weeks 37 to 61 | Adverse Event | 1 | 2 |
| OLE Period: Weeks 37 to 61 | Lack of Efficacy | 3 | 2 |
| OLE Period: Weeks 37 to 61 | Non-compliance with study drug | 1 | 0 |
| OLE Period: Weeks 37 to 61 | Study terminated by sponsor | 8 | 10 |
| OLE Period: Weeks 37 to 61 | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | Rilzabrutinib Then Rilzabrutinib | Total | Placebo Then Rilzabrutinib |
|---|---|---|---|
| Age, Continuous | 50.5 years STANDARD_DEVIATION 14.11 | 51.7 years STANDARD_DEVIATION 14.05 | 52.9 years STANDARD_DEVIATION 14 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 6 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 11 Participants | 7 Participants |
| Race (NIH/OMB) White | 58 Participants | 110 Participants | 52 Participants |
| Sex: Female, Male Female | 36 Participants | 70 Participants | 34 Participants |
| Sex: Female, Male Male | 29 Participants | 61 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 66 | 0 / 65 | 0 / 51 | 0 / 61 | 0 / 112 | 0 / 35 | 0 / 34 | 0 / 69 |
| other Total, other adverse events | 41 / 66 | 47 / 65 | 18 / 51 | 22 / 61 | 40 / 112 | 11 / 35 | 7 / 34 | 18 / 69 |
| serious Total, serious adverse events | 10 / 66 | 6 / 65 | 4 / 51 | 0 / 61 | 4 / 112 | 1 / 35 | 2 / 34 | 3 / 69 |
Outcome results
Primary
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.
Time frame: From Week 29 to Week 37
Population: Analysis was performed on PV mITT which included randomized PV participants who had received at least one dose of study medication and were analyzed according to the treatment they were allocated to at randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Then Rilzabrutinib | 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 | 18.2 percentage of participants |
| Rilzabrutinib Then Rilzabrutinib | 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 | 24.1 percentage of participants |
Comparison: P-value and 95% confidence interval (CI) were based on Cochran-Mantel-Haenszel general association test stratified by disease type (PV or PF) and disease history (newly diagnosed \[\<=6 months prior to screening\] or relapsing \[diagnosed greater than \[\>\] 6 months prior to screening\]).p-value: 0.446995% CI: [-9.037, 20.5]Cochran-Mantel-Haenszel
Primary
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.
Time frame: From Week 29 to Week 37
Population: Analysis was performed on mITT population which included all randomized participants (i.e. PV + PF participants) who had received at least one dose of study medication and were analyzed according to the treatment they were allocated to at randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Then Rilzabrutinib | 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 | 18.2 percentage of participants |
| Rilzabrutinib Then Rilzabrutinib | 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 | 26.2 percentage of participants |
Comparison: P-value and 95% CI were based on Cochran-Mantel-Haenszel general association test stratified by disease type (PV or PF) and disease history (newly diagnosed \[\<=6 months prior to screening\] or relapsing \[diagnosed \>6 months prior to screening\]).p-value: 0.25195% CI: [-5.752, 22.019]Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Baseline, Weeks 5, 13, 25, 37, 61, and 109
Population: Analysis was performed on PV mITT population, based on data collected up to database lock for the blinded treatment period. Here, 'overall number of participants analyzed'=participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Then Rilzabrutinib | Change From Baseline in Autoimmune Bullous Disease Quality of Life (ABQOL) Score at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population | Week 5 | -2.20 score on a scale | Standard Deviation 6.856 |
| Placebo Then Rilzabrutinib | Change From Baseline in Autoimmune Bullous Disease Quality of Life (ABQOL) Score at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population | Week 25 | -5.88 score on a scale | Standard Deviation 7.443 |
| Placebo Then Rilzabrutinib | Change From Baseline in Autoimmune Bullous Disease Quality of Life (ABQOL) Score at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population | Week 13 | -4.04 score on a scale | Standard Deviation 6.831 |
| Placebo Then Rilzabrutinib | Change From Baseline in Autoimmune Bullous Disease Quality of Life (ABQOL) Score at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population | Week 37 | -4.53 score on a scale | Standard Deviation 7.518 |
| Placebo Then Rilzabrutinib | Change From Baseline in Autoimmune Bullous Disease Quality of Life (ABQOL) Score at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population | Week 61 | -7.76 score on a scale | Standard Deviation 6.389 |
| Placebo Then Rilzabrutinib | Change From Baseline in Autoimmune Bullous Disease Quality of Life (ABQOL) Score at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population | Week 109 | -19.00 score on a scale | — |
| Rilzabrutinib Then Rilzabrutinib | Change From Baseline in Autoimmune Bullous Disease Quality of Life (ABQOL) Score at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population | Week 61 | -8.64 score on a scale | Standard Deviation 10.14 |
| Rilzabrutinib Then Rilzabrutinib | Change From Baseline in Autoimmune Bullous Disease Quality of Life (ABQOL) Score at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population | Week 37 | -7.19 score on a scale | Standard Deviation 8.187 |
| Rilzabrutinib Then Rilzabrutinib | Change From Baseline in Autoimmune Bullous Disease Quality of Life (ABQOL) Score at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population | Week 5 | -4.47 score on a scale | Standard Deviation 7.668 |
| Rilzabrutinib Then Rilzabrutinib | Change From Baseline in Autoimmune Bullous Disease Quality of Life (ABQOL) Score at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population | Week 109 | -19.50 score on a scale | Standard Deviation 6.364 |
| Rilzabrutinib Then Rilzabrutinib | Change From Baseline in Autoimmune Bullous Disease Quality of Life (ABQOL) Score at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population | Week 13 | -6.22 score on a scale | Standard Deviation 7.218 |
| Rilzabrutinib Then Rilzabrutinib | Change From Baseline in Autoimmune Bullous Disease Quality of Life (ABQOL) Score at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population | Week 25 | -8.32 score on a scale | Standard Deviation 7.647 |
Secondary
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.
Time frame: Baseline, Weeks 5, 13, 25, 37, 61, and 109
Population: Analysis was performed on mITT population, based on data collected up to database lock for the blinded treatment period. Here, 'overall number of participants analyzed'=participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Then Rilzabrutinib | Change From Baseline in Autoimmune Bullous Disease Quality of Life Score at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | Week 5 | -2.02 score on a scale | Standard Deviation 6.474 |
| Placebo Then Rilzabrutinib | Change From Baseline in Autoimmune Bullous Disease Quality of Life Score at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | Week 13 | -3.18 score on a scale | Standard Deviation 7.262 |
| Placebo Then Rilzabrutinib | Change From Baseline in Autoimmune Bullous Disease Quality of Life Score at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | Week 25 | -5.23 score on a scale | Standard Deviation 7.259 |
| Placebo Then Rilzabrutinib | Change From Baseline in Autoimmune Bullous Disease Quality of Life Score at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | Week 37 | -4.43 score on a scale | Standard Deviation 7.15 |
| Placebo Then Rilzabrutinib | Change From Baseline in Autoimmune Bullous Disease Quality of Life Score at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | Week 61 | -7.40 score on a scale | Standard Deviation 7.416 |
| Placebo Then Rilzabrutinib | Change From Baseline in Autoimmune Bullous Disease Quality of Life Score at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | Week 109 | -13.00 score on a scale | Standard Deviation 6 |
| Rilzabrutinib Then Rilzabrutinib | Change From Baseline in Autoimmune Bullous Disease Quality of Life Score at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | Week 61 | -7.47 score on a scale | Standard Deviation 9.263 |
| Rilzabrutinib Then Rilzabrutinib | Change From Baseline in Autoimmune Bullous Disease Quality of Life Score at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | Week 5 | -4.50 score on a scale | Standard Deviation 7.324 |
| Rilzabrutinib Then Rilzabrutinib | Change From Baseline in Autoimmune Bullous Disease Quality of Life Score at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | Week 37 | -7.00 score on a scale | Standard Deviation 7.843 |
| Rilzabrutinib Then Rilzabrutinib | Change From Baseline in Autoimmune Bullous Disease Quality of Life Score at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | Week 13 | -5.93 score on a scale | Standard Deviation 7.168 |
| Rilzabrutinib Then Rilzabrutinib | Change From Baseline in Autoimmune Bullous Disease Quality of Life Score at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | Week 109 | -19.50 score on a scale | Standard Deviation 6.364 |
| Rilzabrutinib Then Rilzabrutinib | Change From Baseline in Autoimmune Bullous Disease Quality of Life Score at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | Week 25 | -7.57 score on a scale | Standard Deviation 7.667 |
Secondary
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.
Time frame: Baseline, Weeks 5, 13, 25, 37, 61, and 109
Population: Analysis was performed on mITT population, based on data collected up to database lock for the blinded treatment period. Here, 'number analyzed' = participants with available data for each specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Then Rilzabrutinib | Change From Baseline in Pemphigus Disease Area Index Score at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | Week 13 | -11.253 units on a scale | Standard Deviation 12.1328 |
| Placebo Then Rilzabrutinib | Change From Baseline in Pemphigus Disease Area Index Score at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | Week 37 | -12.918 units on a scale | Standard Deviation 11.026 |
| Placebo Then Rilzabrutinib | Change From Baseline in Pemphigus Disease Area Index Score at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | Week 5 | -7.870 units on a scale | Standard Deviation 12.5361 |
| Placebo Then Rilzabrutinib | Change From Baseline in Pemphigus Disease Area Index Score at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | Week 61 | -13.793 units on a scale | Standard Deviation 8.9794 |
| Placebo Then Rilzabrutinib | Change From Baseline in Pemphigus Disease Area Index Score at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | Week 109 | -23.967 units on a scale | Standard Deviation 16.4628 |
| Placebo Then Rilzabrutinib | Change From Baseline in Pemphigus Disease Area Index Score at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | Week 25 | -11.722 units on a scale | Standard Deviation 13.258 |
| Rilzabrutinib Then Rilzabrutinib | Change From Baseline in Pemphigus Disease Area Index Score at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | Week 109 | -18.250 units on a scale | Standard Deviation 9.8288 |
| Rilzabrutinib Then Rilzabrutinib | Change From Baseline in Pemphigus Disease Area Index Score at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | Week 5 | -7.161 units on a scale | Standard Deviation 6.5918 |
| Rilzabrutinib Then Rilzabrutinib | Change From Baseline in Pemphigus Disease Area Index Score at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | Week 13 | -13.139 units on a scale | Standard Deviation 10.3317 |
| Rilzabrutinib Then Rilzabrutinib | Change From Baseline in Pemphigus Disease Area Index Score at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | Week 25 | -14.174 units on a scale | Standard Deviation 11.1997 |
| Rilzabrutinib Then Rilzabrutinib | Change From Baseline in Pemphigus Disease Area Index Score at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | Week 37 | -13.442 units on a scale | Standard Deviation 10.2669 |
| Rilzabrutinib Then Rilzabrutinib | Change From Baseline in Pemphigus Disease Area Index Score at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | Week 61 | -14.649 units on a scale | Standard Deviation 11.4991 |
Secondary
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.
Time frame: Baseline, Weeks 5, 13, 25, 37, 61, and 109
Population: Analysis was performed on PV mITT population, based on data collected up to database lock for the blinded treatment period. Here, 'number analyzed' = participants with available data for each specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Then Rilzabrutinib | Change From Baseline in Pemphigus Disease Area Index Score at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population | Week 5 | -7.567 units on a scale | Standard Deviation 12.631 |
| Placebo Then Rilzabrutinib | Change From Baseline in Pemphigus Disease Area Index Score at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population | Week 25 | -11.333 units on a scale | Standard Deviation 13.8064 |
| Placebo Then Rilzabrutinib | Change From Baseline in Pemphigus Disease Area Index Score at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population | Week 109 | -21.300 units on a scale | — |
| Placebo Then Rilzabrutinib | Change From Baseline in Pemphigus Disease Area Index Score at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population | Week 37 | -13.000 units on a scale | Standard Deviation 10.9202 |
| Placebo Then Rilzabrutinib | Change From Baseline in Pemphigus Disease Area Index Score at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population | Week 13 | -11.076 units on a scale | Standard Deviation 11.4549 |
| Placebo Then Rilzabrutinib | Change From Baseline in Pemphigus Disease Area Index Score at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population | Week 61 | -12.900 units on a scale | Standard Deviation 6.6418 |
| Rilzabrutinib Then Rilzabrutinib | Change From Baseline in Pemphigus Disease Area Index Score at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population | Week 13 | -13.925 units on a scale | Standard Deviation 10.1497 |
| Rilzabrutinib Then Rilzabrutinib | Change From Baseline in Pemphigus Disease Area Index Score at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population | Week 109 | -18.250 units on a scale | Standard Deviation 9.8288 |
| Rilzabrutinib Then Rilzabrutinib | Change From Baseline in Pemphigus Disease Area Index Score at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population | Week 5 | -7.224 units on a scale | Standard Deviation 6.9832 |
| Rilzabrutinib Then Rilzabrutinib | Change From Baseline in Pemphigus Disease Area Index Score at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population | Week 61 | -16.475 units on a scale | Standard Deviation 10.1585 |
| Rilzabrutinib Then Rilzabrutinib | Change From Baseline in Pemphigus Disease Area Index Score at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population | Week 25 | -15.292 units on a scale | Standard Deviation 10.5552 |
| Rilzabrutinib Then Rilzabrutinib | Change From Baseline in Pemphigus Disease Area Index Score at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population | Week 37 | -14.167 units on a scale | Standard Deviation 9.8679 |
Secondary
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.
Time frame: Baseline, Weeks 5, 13, 25, 37, 61, and 109
Population: For this OM, the planned data collection and analysis was not performed because of early termination of the study.
Secondary
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 frame: Baseline, Weeks 5, 13, 25, 37, 61, and 109
Population: For this OM, the planned data collection and analysis was not performed because of early termination of the study.
Secondary
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.
Time frame: Baseline to Week 61 and Baseline to Week 109
Population: Analysis was performed on mITT population, based on data collected up to database lock for the blinded treatment period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Then Rilzabrutinib | Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Baseline to Weeks 61 and 109: mITT Population | Baseline to Week 61 | 17.6 days | Standard Deviation 38.56 |
| Placebo Then Rilzabrutinib | Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Baseline to Weeks 61 and 109: mITT Population | Baseline to Week 109 | 49.5 days | Standard Deviation 106.14 |
| Rilzabrutinib Then Rilzabrutinib | Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Baseline to Weeks 61 and 109: mITT Population | Baseline to Week 61 | 33.5 days | Standard Deviation 55.06 |
| Rilzabrutinib Then Rilzabrutinib | Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Baseline to Weeks 61 and 109: mITT Population | Baseline to Week 109 | 72.5 days | Standard Deviation 125.6 |
Secondary
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.
Time frame: Baseline to Week 61 and Baseline to Week 109
Population: Analysis was performed on PV mITT population, based on data collected up to database lock for the blinded treatment period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Then Rilzabrutinib | Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Baseline to Weeks 61 and 109: PV mITT Population | Baseline to Week 61 | 13.5 days | Standard Deviation 35.33 |
| Placebo Then Rilzabrutinib | Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Baseline to Weeks 61 and 109: PV mITT Population | Baseline to Week 109 | 28.4 days | Standard Deviation 77.54 |
| Rilzabrutinib Then Rilzabrutinib | Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Baseline to Weeks 61 and 109: PV mITT Population | Baseline to Week 61 | 28.6 days | Standard Deviation 52.33 |
| Rilzabrutinib Then Rilzabrutinib | Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Baseline to Weeks 61 and 109: PV mITT Population | Baseline to Week 109 | 60.7 days | Standard Deviation 118.87 |
Secondary
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.
Time frame: From Week 37 to Week 61
Population: Analysis was performed on mITT population, based on data collected up to database lock for the blinded treatment period. Here, overall number of participants analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Then Rilzabrutinib | Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Week 37 to Week 61: mITT Population | 22.8 days | Standard Deviation 42.58 |
| Rilzabrutinib Then Rilzabrutinib | Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Week 37 to Week 61: mITT Population | 35.3 days | Standard Deviation 56.32 |
Secondary
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.
Time frame: From Week 37 to Week 61
Population: Analysis was performed on PV mITT population, based on data collected up to database lock for the blinded treatment period. Here, overall number of participants analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Then Rilzabrutinib | Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Week 37 to Week 61: PV mITT Population | 17.7 days | Standard Deviation 39.6 |
| Rilzabrutinib Then Rilzabrutinib | Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Week 37 to Week 61: PV mITT Population | 30.5 days | Standard Deviation 53.92 |
Secondary
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.
Time frame: Baseline to Week 37
Population: Analysis was performed on mITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Then Rilzabrutinib | Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: mITT Population | 34.0 days | Standard Deviation 54.36 |
| Rilzabrutinib Then Rilzabrutinib | Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: mITT Population | 54.3 days | Standard Deviation 68.76 |
Secondary
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.
Time frame: Baseline to Week 37
Population: Analysis was performed on PV mITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Then Rilzabrutinib | Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: PV mITT Population | 34.1 days | Standard Deviation 51.58 |
| Rilzabrutinib Then Rilzabrutinib | Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: PV mITT Population | 50.5 days | Standard Deviation 67.1 |
Secondary
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.
Time frame: Baseline to Weeks 61 and Baseline to Week 109
Population: Analysis was performed on mITT population, based on data collected up to database lock for the blinded treatment period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Then Rilzabrutinib | Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Weeks 61 and 109: mITT Population | Baseline to Week 61 | 78.1 days | Standard Deviation 98.68 |
| Placebo Then Rilzabrutinib | Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Weeks 61 and 109: mITT Population | Baseline to Week 109 | 124.6 days | Standard Deviation 153.76 |
| Rilzabrutinib Then Rilzabrutinib | Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Weeks 61 and 109: mITT Population | Baseline to Week 61 | 120.4 days | Standard Deviation 124.38 |
| Rilzabrutinib Then Rilzabrutinib | Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Weeks 61 and 109: mITT Population | Baseline to Week 109 | 171.6 days | Standard Deviation 186.66 |
Secondary
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.
Time frame: Baseline to Week 61 and Baseline to Week 109
Population: Analysis was performed on PV mITT population, based on data collected up to database lock for the blinded treatment period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Then Rilzabrutinib | Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Weeks 61 and 109: PV mITT Population | Baseline to Week 61 | 73.8 days | Standard Deviation 95.35 |
| Placebo Then Rilzabrutinib | Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Weeks 61 and 109: PV mITT Population | Baseline to Week 109 | 102.2 days | Standard Deviation 133.22 |
| Rilzabrutinib Then Rilzabrutinib | Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Weeks 61 and 109: PV mITT Population | Baseline to Week 61 | 112.2 days | Standard Deviation 120.65 |
| Rilzabrutinib Then Rilzabrutinib | Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Weeks 61 and 109: PV mITT Population | Baseline to Week 109 | 157.0 days | Standard Deviation 179.71 |
Secondary
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.
Time frame: From Week 37 to Week 61
Population: Analysis was performed on mITT population, based on data collected up to database lock for the blinded treatment period. Here, overall number of participants analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Then Rilzabrutinib | Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Week 37 to Week 61: mITT Population | 57.1 days | Standard Deviation 59.99 |
| Rilzabrutinib Then Rilzabrutinib | Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Week 37 to Week 61: mITT Population | 67.1 days | Standard Deviation 68.03 |
Secondary
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.
Time frame: From Week 37 to Week 61
Population: Analysis was performed on PV mITT population, based on data collected up to database lock for the blinded treatment period. Here, overall number of participants analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Then Rilzabrutinib | Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Week 37 to Week 61: PV mITT Population | 52.0 days | Standard Deviation 59.01 |
| Rilzabrutinib Then Rilzabrutinib | Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Week 37 to Week 61: PV mITT Population | 62.5 days | Standard Deviation 67.59 |
Secondary
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.
Time frame: Baseline to Week 37
Population: Analysis was performed on mITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Then Rilzabrutinib | Cumulative Oral Corticosteroid Dose From Baseline to Week 37: mITT Population | 5392.2 milligrams | Standard Deviation 2993.02 |
| Rilzabrutinib Then Rilzabrutinib | Cumulative Oral Corticosteroid Dose From Baseline to Week 37: mITT Population | 4860.2 milligrams | Standard Deviation 2545.32 |
Secondary
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.
Time frame: Baseline to Week 37
Population: Analysis was performed on PV mITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Then Rilzabrutinib | Cumulative Oral Corticosteroid Dose From Baseline to Week 37: PV mITT Population | 5653.2 milligrams | Standard Deviation 3155.97 |
| Rilzabrutinib Then Rilzabrutinib | Cumulative Oral Corticosteroid Dose From Baseline to Week 37: PV mITT Population | 5131.4 milligrams | Standard Deviation 2623.92 |
Secondary
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.
Time frame: At Week 37
Population: Analysis was performed on mITT population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Then Rilzabrutinib | Glucocorticoid Toxicity Index - Cumulative Worsening Score and Aggregate Improvement Score at Week 37: mITT Population | CWS | 51.68 units on a scale | Standard Error 7.368 |
| Placebo Then Rilzabrutinib | Glucocorticoid Toxicity Index - Cumulative Worsening Score and Aggregate Improvement Score at Week 37: mITT Population | AIS | 8.63 units on a scale | Standard Error 5.73 |
| Rilzabrutinib Then Rilzabrutinib | Glucocorticoid Toxicity Index - Cumulative Worsening Score and Aggregate Improvement Score at Week 37: mITT Population | CWS | 68.15 units on a scale | Standard Error 6.732 |
| Rilzabrutinib Then Rilzabrutinib | Glucocorticoid Toxicity Index - Cumulative Worsening Score and Aggregate Improvement Score at Week 37: mITT Population | AIS | 18.23 units on a scale | Standard Error 5.236 |
Secondary
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.
Time frame: At Week 37
Population: Analysis was performed on PV mITT population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Then Rilzabrutinib | Glucocorticoid Toxicity Index (GTI) - Cumulative Worsening Score (CWS) and Aggregate Improvement Score (AIS) at Week 37: PV mITT Population | CWS | 54.46 units on a scale | Standard Error 8.136 |
| Placebo Then Rilzabrutinib | Glucocorticoid Toxicity Index (GTI) - Cumulative Worsening Score (CWS) and Aggregate Improvement Score (AIS) at Week 37: PV mITT Population | AIS | 9.42 units on a scale | Standard Error 6.516 |
| Rilzabrutinib Then Rilzabrutinib | Glucocorticoid Toxicity Index (GTI) - Cumulative Worsening Score (CWS) and Aggregate Improvement Score (AIS) at Week 37: PV mITT Population | CWS | 73.60 units on a scale | Standard Error 7.397 |
| Rilzabrutinib Then Rilzabrutinib | Glucocorticoid Toxicity Index (GTI) - Cumulative Worsening Score (CWS) and Aggregate Improvement Score (AIS) at Week 37: PV mITT Population | AIS | 19.95 units on a scale | Standard Error 5.924 |
Secondary
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.
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)
Population: Analysis was performed on safety population which included all participants who had received at least one dose of study medication and were analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo Then Rilzabrutinib | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TEAE | 54 Participants |
| Placebo Then Rilzabrutinib | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TESAE | 10 Participants |
| Rilzabrutinib Then Rilzabrutinib | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TEAE | 55 Participants |
| Rilzabrutinib Then Rilzabrutinib | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TESAE | 6 Participants |
| OLE Period: Placebo Then Rilzabrutinib | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TEAE | 33 Participants |
| OLE Period: Placebo Then Rilzabrutinib | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TESAE | 4 Participants |
| OLE Period: Rilzabrutinib Then Rilzabrutinib | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TEAE | 35 Participants |
| OLE Period: Rilzabrutinib Then Rilzabrutinib | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TESAE | 0 Participants |
| LTE Period: Placebo Then Rilzabrutinib | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TEAE | 18 Participants |
| LTE Period: Placebo Then Rilzabrutinib | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TESAE | 1 Participants |
| LTE Period: Rilzabrutinib Then Rilzabrutinib | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TEAE | 14 Participants |
| LTE Period: Rilzabrutinib Then Rilzabrutinib | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TESAE | 2 Participants |
Secondary
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.
Time frame: From Week 29 to Week 37
Population: Analysis was performed on mITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Then Rilzabrutinib | Percentage of Participants Who Achieved Complete Remission With a Corticosteroids Dose of <=5 mg/Day From Week 29 to Week 37: mITT Population | 12.1 percentage of participants |
| Rilzabrutinib Then Rilzabrutinib | Percentage of Participants Who Achieved Complete Remission With a Corticosteroids Dose of <=5 mg/Day From Week 29 to Week 37: mITT Population | 26.2 percentage of participants |
Secondary
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.
Time frame: From Week 29 to Week 37
Population: Analysis was performed on PV mITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Then Rilzabrutinib | Percentage of Participants Who Achieved Complete Remission With a Corticosteroids Dose of <=5 mg/Day From Week 29 to Week 37: PV mITT Population | 10.9 percentage of participants |
| Rilzabrutinib Then Rilzabrutinib | Percentage of Participants Who Achieved Complete Remission With a Corticosteroids Dose of <=5 mg/Day From Week 29 to Week 37: PV mITT Population | 24.1 percentage of participants |
Secondary
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.
Time frame: From Week 29 to Week 37
Population: Analysis was performed on PV mITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Then Rilzabrutinib | 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 | 29.1 percentage of participants |
| Rilzabrutinib Then Rilzabrutinib | 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 | 35.2 percentage of participants |
Secondary
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.
Time frame: From Week 29 to Week 37
Population: Analysis was performed on mITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Then Rilzabrutinib | 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 | 27.3 percentage of participants |
| Rilzabrutinib Then Rilzabrutinib | 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 | 38.5 percentage of participants |
Secondary
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.
Time frame: At Week 37
Population: Analysis was performed on mITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Then Rilzabrutinib | 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 | 59.1 percentage of participants |
| Rilzabrutinib Then Rilzabrutinib | 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 | 36.9 percentage of participants |
Secondary
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.
Time frame: At Week 37
Population: Analysis was performed on PV mITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Then Rilzabrutinib | 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 | 58.2 percentage of participants |
| Rilzabrutinib Then Rilzabrutinib | 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 | 35.2 percentage of participants |
Secondary
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.
Time frame: From initial CDA up to Week 37 (i.e., during any time from Baseline up to Week 37)
Population: Analysis was performed on mITT population. Here, overall number of participants analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Then Rilzabrutinib | Percentage of Participants With at Least One Disease Relapse/Flare From Initial Control of Disease Activity to Week 37: mITT Population | 43.5 percentage of participants |
| Rilzabrutinib Then Rilzabrutinib | Percentage of Participants With at Least One Disease Relapse/Flare From Initial Control of Disease Activity to Week 37: mITT Population | 29.7 percentage of participants |
Secondary
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.
Time frame: From initial CDA up to Week 37 (i.e., during any time from Baseline up to Week 37)
Population: Analysis was performed on PV mITT population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Then Rilzabrutinib | Percentage of Participants With at Least One Disease Relapse/Flare From Initial Control of Disease Activity to Week 37: PV mITT Population | 43.1 percentage of participants |
| Rilzabrutinib Then Rilzabrutinib | Percentage of Participants With at Least One Disease Relapse/Flare From Initial Control of Disease Activity to Week 37: PV mITT Population | 28.3 percentage of participants |
Secondary
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.
Time frame: At Weeks 5, 13, 25, 37, 61, and 109
Population: Analysis was performed on mITT population, based on data collected up to database lock for the blinded treatment period. Here, 'number analyzed' = participants with available data for each specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Then Rilzabrutinib | Percentage of Participants With Autoimmune Bullous Disease Quality of Life Score of Zero at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | Week 5 | 0.0 percentage of participants |
| Placebo Then Rilzabrutinib | Percentage of Participants With Autoimmune Bullous Disease Quality of Life Score of Zero at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | Week 13 | 1.8 percentage of participants |
| Placebo Then Rilzabrutinib | Percentage of Participants With Autoimmune Bullous Disease Quality of Life Score of Zero at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | Week 25 | 3.7 percentage of participants |
| Placebo Then Rilzabrutinib | Percentage of Participants With Autoimmune Bullous Disease Quality of Life Score of Zero at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | Week 37 | 6.4 percentage of participants |
| Placebo Then Rilzabrutinib | Percentage of Participants With Autoimmune Bullous Disease Quality of Life Score of Zero at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | Week 61 | 12.0 percentage of participants |
| Placebo Then Rilzabrutinib | Percentage of Participants With Autoimmune Bullous Disease Quality of Life Score of Zero at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | Week 109 | 33.3 percentage of participants |
| Rilzabrutinib Then Rilzabrutinib | Percentage of Participants With Autoimmune Bullous Disease Quality of Life Score of Zero at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | Week 61 | 8.3 percentage of participants |
| Rilzabrutinib Then Rilzabrutinib | Percentage of Participants With Autoimmune Bullous Disease Quality of Life Score of Zero at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | Week 5 | 1.7 percentage of participants |
| Rilzabrutinib Then Rilzabrutinib | Percentage of Participants With Autoimmune Bullous Disease Quality of Life Score of Zero at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | Week 37 | 5.1 percentage of participants |
| Rilzabrutinib Then Rilzabrutinib | Percentage of Participants With Autoimmune Bullous Disease Quality of Life Score of Zero at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | Week 13 | 5.0 percentage of participants |
| Rilzabrutinib Then Rilzabrutinib | Percentage of Participants With Autoimmune Bullous Disease Quality of Life Score of Zero at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | Week 109 | 50.0 percentage of participants |
| Rilzabrutinib Then Rilzabrutinib | Percentage of Participants With Autoimmune Bullous Disease Quality of Life Score of Zero at Weeks 5, 13, 25, 37, 61, and 109: mITT Population | Week 25 | 6.8 percentage of participants |
Secondary
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.
Time frame: At Weeks 5, 13, 25, 37, 61, and 109
Population: Analysis was performed on PV mITT population, based on data collected up to database lock for the blinded treatment period. Here, 'number analyzed' = participants with available data for each specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Then Rilzabrutinib | 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 | Week 5 | 0.0 percentage of participants |
| Placebo Then Rilzabrutinib | 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 | Week 13 | 2.1 percentage of participants |
| Placebo Then Rilzabrutinib | 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 | Week 25 | 4.4 percentage of participants |
| Placebo Then Rilzabrutinib | 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 | Week 37 | 7.9 percentage of participants |
| Placebo Then Rilzabrutinib | 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 | Week 61 | 11.8 percentage of participants |
| Placebo Then Rilzabrutinib | 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 | Week 109 | 0.0 percentage of participants |
| Rilzabrutinib Then Rilzabrutinib | 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 | Week 61 | 12.0 percentage of participants |
| Rilzabrutinib Then Rilzabrutinib | 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 | Week 5 | 2.0 percentage of participants |
| Rilzabrutinib Then Rilzabrutinib | 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 | Week 37 | 4.2 percentage of participants |
| Rilzabrutinib Then Rilzabrutinib | 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 | Week 13 | 4.0 percentage of participants |
| Rilzabrutinib Then Rilzabrutinib | 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 | Week 109 | 50.0 percentage of participants |
| Rilzabrutinib Then Rilzabrutinib | 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 | Week 25 | 4.2 percentage of participants |
Secondary
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.
Time frame: Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, and 109
Population: Analysis was performed on mITT population. Here, 'number analyzed' = participants with available data for each specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Then Rilzabrutinib | 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 | Baseline: Anti-dsg1 | 132.2 units/milliliter | Standard Deviation 275.92 |
| Placebo Then Rilzabrutinib | 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 | Baseline: Anti-dsg3 | 328.8 units/milliliter | Standard Deviation 651.84 |
| Placebo Then Rilzabrutinib | 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 | Change at Week 13: Anti-dsg3 | 166.1 units/milliliter | Standard Deviation 302.25 |
| Placebo Then Rilzabrutinib | 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 | Change at Week 13: Anti-dsg1 | 73.7 units/milliliter | Standard Deviation 116.08 |
| Placebo Then Rilzabrutinib | 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 | Change at Week 25: Anti-dsg1 | 65.6 units/milliliter | Standard Deviation 105.99 |
| Placebo Then Rilzabrutinib | 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 | Change at Week 25: Anti-dsg3 | 182.4 units/milliliter | Standard Deviation 298.18 |
| Placebo Then Rilzabrutinib | 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 | Change at Week 37: Anti-dsg1 | 59.5 units/milliliter | Standard Deviation 101.58 |
| Placebo Then Rilzabrutinib | 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 | Change at Week 37: Anti-dsg3 | 167.8 units/milliliter | Standard Deviation 293.78 |
| Placebo Then Rilzabrutinib | 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 | Change at Week 49: Anti-dsg1 | 31.9 units/milliliter | Standard Deviation 53.27 |
| Placebo Then Rilzabrutinib | 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 | Change at Week 49: Anti-dsg3 | 163.4 units/milliliter | Standard Deviation 298.38 |
| Placebo Then Rilzabrutinib | 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 | Change at Week 61: Anti-dsg1 | 41.5 units/milliliter | Standard Deviation 68.66 |
| Placebo Then Rilzabrutinib | 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 | Change at Week 61: Anti-dsg3 | 165.3 units/milliliter | Standard Deviation 372.1 |
| Placebo Then Rilzabrutinib | 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 | Change at Week 73: Anti-dsg1 | 43.5 units/milliliter | Standard Deviation 87.58 |
| Placebo Then Rilzabrutinib | 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 | Change at Week 73: Anti-dsg3 | 165.2 units/milliliter | Standard Deviation 358.15 |
| Placebo Then Rilzabrutinib | 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 | Change at Week 85: Anti-dsg1 | 22.3 units/milliliter | Standard Deviation 39.62 |
| Placebo Then Rilzabrutinib | 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 | Change at Week 85: Anti-dsg3 | 116.9 units/milliliter | Standard Deviation 296.51 |
| Placebo Then Rilzabrutinib | 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 | Change at Week 97: Anti-dsg1 | 21.9 units/milliliter | Standard Deviation 46.36 |
| Placebo Then Rilzabrutinib | 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 | Change at Week 97: Anti-dsg3 | 107.6 units/milliliter | Standard Deviation 254.47 |
| Placebo Then Rilzabrutinib | 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 | Change at Week 109: Anti-dsg1 | 4.7 units/milliliter | Standard Deviation 4.73 |
| Placebo Then Rilzabrutinib | 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 | Change at Week 109: Anti-dsg3 | 1.0 units/milliliter | Standard Deviation 1.73 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Change at Week 97: Anti-dsg3 | 76.0 units/milliliter | Standard Deviation 161.13 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Baseline: Anti-dsg1 | 141.7 units/milliliter | Standard Deviation 366.74 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Change at Week 61: Anti-dsg1 | 44.6 units/milliliter | Standard Deviation 88.74 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Change at Week 13: Anti-dsg1 | 39.8 units/milliliter | Standard Deviation 102.35 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Change at Week 85: Anti-dsg3 | 97.9 units/milliliter | Standard Deviation 170.97 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Baseline: Anti-dsg3 | 385.8 units/milliliter | Standard Deviation 632.71 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Change at Week 61: Anti-dsg3 | 159.2 units/milliliter | Standard Deviation 249.62 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Change at Week 13: Anti-dsg3 | 82.5 units/milliliter | Standard Deviation 138.29 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Change at Week 109: Anti-dsg3 | 94.0 units/milliliter | Standard Deviation 115.97 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Change at Week 25: Anti-dsg1 | 40.5 units/milliliter | Standard Deviation 106.1 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Change at Week 73: Anti-dsg1 | 48.5 units/milliliter | Standard Deviation 139.91 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Change at Week 25: Anti-dsg3 | 124.3 units/milliliter | Standard Deviation 320.96 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Change at Week 97: Anti-dsg1 | 52.2 units/milliliter | Standard Deviation 141.86 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Change at Week 37: Anti-dsg1 | 37.0 units/milliliter | Standard Deviation 68.28 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Change at Week 73: Anti-dsg3 | 112.0 units/milliliter | Standard Deviation 171.9 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Change at Week 37: Anti-dsg3 | 176.5 units/milliliter | Standard Deviation 362.67 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Change at Week 109: Anti-dsg1 | 2.0 units/milliliter | Standard Deviation 0 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Change at Week 49: Anti-dsg1 | 44.1 units/milliliter | Standard Deviation 102.07 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Change at Week 85: Anti-dsg1 | 42.1 units/milliliter | Standard Deviation 105.9 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Change at Week 49: Anti-dsg3 | 216.4 units/milliliter | Standard Deviation 520.01 |
Secondary
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.
Time frame: Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, and 109
Population: Analysis was performed on PV mITT population. Here, 'number analyzed' = participants with available data for each specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Then Rilzabrutinib | 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 | Change at Week 49: Anti-dsg3 | 215.6 units/milliliter | Standard Deviation 327.22 |
| Placebo Then Rilzabrutinib | 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 | Change at Week 25: Anti-dsg1 | 48.2 units/milliliter | Standard Deviation 93.15 |
| Placebo Then Rilzabrutinib | 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 | Change at Week 61: Anti-dsg1 | 12.0 units/milliliter | Standard Deviation 20.61 |
| Placebo Then Rilzabrutinib | 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 | Baseline: Anti-dsg1 | 108.4 units/milliliter | Standard Deviation 288.97 |
| Placebo Then Rilzabrutinib | 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 | Change at Week 61: Anti-dsg3 | 252.3 units/milliliter | Standard Deviation 439.45 |
| Placebo Then Rilzabrutinib | 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 | Change at Week 25: Anti-dsg3 | 218.6 units/milliliter | Standard Deviation 314.74 |
| Placebo Then Rilzabrutinib | 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 | Change at Week 73: Anti-dsg1 | 12.8 units/milliliter | Standard Deviation 23.21 |
| Placebo Then Rilzabrutinib | 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 | Change at Week 13: Anti-dsg1 | 60.6 units/milliliter | Standard Deviation 116.32 |
| Placebo Then Rilzabrutinib | 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 | Change at Week 73: Anti-dsg3 | 237.1 units/milliliter | Standard Deviation 412.33 |
| Placebo Then Rilzabrutinib | 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 | Change at Week 37: Anti-dsg1 | 42.0 units/milliliter | Standard Deviation 95.02 |
| Placebo Then Rilzabrutinib | 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 | Change at Week 85: Anti-dsg1 | 11.7 units/milliliter | Standard Deviation 24.31 |
| Placebo Then Rilzabrutinib | 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 | Change at Week 109: Anti-dsg1 | 1.0 units/milliliter | — |
| Placebo Then Rilzabrutinib | 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 | Change at Week 85: Anti-dsg3 | 169.9 units/milliliter | Standard Deviation 349.29 |
| Placebo Then Rilzabrutinib | 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 | Change at Week 37: Anti-dsg3 | 204.4 units/milliliter | Standard Deviation 313.26 |
| Placebo Then Rilzabrutinib | 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 | Change at Week 97: Anti-dsg1 | 3.6 units/milliliter | Standard Deviation 5.27 |
| Placebo Then Rilzabrutinib | 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 | Change at Week 13: Anti-dsg3 | 197.1 units/milliliter | Standard Deviation 320.37 |
| Placebo Then Rilzabrutinib | 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 | Change at Week 97: Anti-dsg3 | 193.0 units/milliliter | Standard Deviation 330.12 |
| Placebo Then Rilzabrutinib | 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 | Change at Week 49: Anti-dsg1 | 12.1 units/milliliter | Standard Deviation 18.66 |
| Placebo Then Rilzabrutinib | 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 | Change at Week 109: Anti-dsg3 | 0.0 units/milliliter | — |
| Placebo Then Rilzabrutinib | 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 | Baseline: Anti-dsg3 | 392.5 units/milliliter | Standard Deviation 697.52 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Change at Week 109: Anti-dsg3 | 94.0 units/milliliter | Standard Deviation 115.97 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Baseline: Anti-dsg1 | 85.9 units/milliliter | Standard Deviation 139.17 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Baseline: Anti-dsg3 | 464.1 units/milliliter | Standard Deviation 668.22 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Change at Week 13: Anti-dsg1 | 15.4 units/milliliter | Standard Deviation 34.2 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Change at Week 13: Anti-dsg3 | 99.8 units/milliliter | Standard Deviation 146.65 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Change at Week 25: Anti-dsg1 | 17.5 units/milliliter | Standard Deviation 37.44 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Change at Week 25: Anti-dsg3 | 153.7 units/milliliter | Standard Deviation 351.56 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Change at Week 37: Anti-dsg1 | 24.1 units/milliliter | Standard Deviation 60.01 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Change at Week 37: Anti-dsg3 | 213.9 units/milliliter | Standard Deviation 389.85 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Change at Week 49: Anti-dsg1 | 17.1 units/milliliter | Standard Deviation 31.99 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Change at Week 49: Anti-dsg3 | 277.1 units/milliliter | Standard Deviation 575.77 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Change at Week 61: Anti-dsg1 | 12.5 units/milliliter | Standard Deviation 26.08 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Change at Week 61: Anti-dsg3 | 223.5 units/milliliter | Standard Deviation 271.69 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Change at Week 73: Anti-dsg1 | 10.5 units/milliliter | Standard Deviation 26.34 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Change at Week 73: Anti-dsg3 | 157.6 units/milliliter | Standard Deviation 186.82 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Change at Week 85: Anti-dsg1 | 14.2 units/milliliter | Standard Deviation 28.05 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Change at Week 85: Anti-dsg3 | 132.4 units/milliliter | Standard Deviation 189.76 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Change at Week 97: Anti-dsg1 | 4.7 units/milliliter | Standard Deviation 8.6 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Change at Week 109: Anti-dsg1 | 2.0 units/milliliter | Standard Deviation 0 |
| Rilzabrutinib Then Rilzabrutinib | 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 | Change at Week 97: Anti-dsg3 | 95.4 units/milliliter | Standard Deviation 180.66 |
Secondary
Pharmacokinetics (PK): Plasma Concentration of Rilzabrutinib
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
Population: Analysis was performed on PK population which included all participants who had received at least one dose of study medication and had sufficient data for PK analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Then Rilzabrutinib | Pharmacokinetics (PK): Plasma Concentration of Rilzabrutinib | Day 1: 2-hour post-dose | 273.13 nanograms per milliliter | Standard Deviation 264.136 |
| Placebo Then Rilzabrutinib | Pharmacokinetics (PK): Plasma Concentration of Rilzabrutinib | Day 1: pre-dose | NA nanograms per milliliter | — |
Secondary
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.
Time frame: Baseline to Week 37
Population: Analysis was performed on mITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo Then Rilzabrutinib | Time to First Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: mITT Population | NA days |
| Rilzabrutinib Then Rilzabrutinib | Time to First Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: mITT Population | 197.0 days |
Secondary
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 frame: Baseline to Week 37
Population: Analysis was performed on PV mITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo Then Rilzabrutinib | Time to First Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: PV mITT Population | 252.0 days |
| Rilzabrutinib Then Rilzabrutinib | Time to First Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: PV mITT Population | 197.0 days |
Secondary
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.
Time frame: Baseline to Week 61 and Baseline to Week 109
Population: For this OM, the planned data collection and analysis was not performed because of early termination of the study.
Secondary
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.
Time frame: From initial CDA up to Week 37 (i.e., during any time from Baseline up to Week 37)
Population: Analysis was performed on mITT population. Here, overall number of participants analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo Then Rilzabrutinib | Time to Initial Relapse/Flare From Initial Control of Disease Activity to Week 37: mITT Population | 243.0 days |
| Rilzabrutinib Then Rilzabrutinib | Time to Initial Relapse/Flare From Initial Control of Disease Activity to Week 37: mITT Population | NA days |
Secondary
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 frame: From initial CDA up to Week 37 (i.e., during any time from Baseline up to Week 37)
Population: Analysis was performed on PV mITT population. Here, overall number of participants analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo Then Rilzabrutinib | Time to Initial Relapse/Flare From Initial Control of Disease Activity to Week 37: PV mITT Population | 243.0 days |
| Rilzabrutinib Then Rilzabrutinib | Time to Initial Relapse/Flare From Initial Control of Disease Activity to Week 37: PV mITT Population | NA days |
Secondary
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.
Time frame: From initial CDA up to Week 37 (i.e., during any time from Baseline up to Week 37)
Population: Analysis was performed on PV mITT population. Here, overall number of participants analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Then Rilzabrutinib | Total Number of Disease Relapses/Flares From Initial Control of Disease Activity (CDA) to Week 37: PV mITT Population | 0.6 relapses | Standard Deviation 0.96 |
| Rilzabrutinib Then Rilzabrutinib | Total Number of Disease Relapses/Flares From Initial Control of Disease Activity (CDA) to Week 37: PV mITT Population | 0.3 relapses | Standard Deviation 0.55 |
Secondary
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.
Time frame: From initial CDA up to Week 37 (i.e., during any time from Baseline up to Week 37)
Population: Analysis was performed on mITT population. Here, overall number of participants analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Then Rilzabrutinib | Total Number of Disease Relapses/Flares From Initial Control of Disease Activity to Week 37: mITT Population | 0.6 relapses | Standard Deviation 0.94 |
| Rilzabrutinib Then Rilzabrutinib | Total Number of Disease Relapses/Flares From Initial Control of Disease Activity to Week 37: mITT Population | 0.3 relapses | Standard Deviation 0.54 |