A Phase 3 interventional study of Rilzabrutinib and Placebo in Pemphigus, sponsored by Principia Biopharma, a Sanofi Company. Terminated at 88 sites in 19 countries. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2023-08-02.
Sponsored by Principia Biopharma, a Sanofi Company (part of Sanofi) · Phase 3, Interventional, and Treatment
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.
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).
76 studies on the registry are indexed under Pemphigus; 18 are open to participants now.
This study's enrollment of 131 is above the median of 30 across 53 interventional studies indexed under Pemphigus.
Browse Pemphigus studies →Principia Biopharma, a Sanofi Company is the lead sponsor of 10 studies on the registry; none are open to participants now.
Of its 8 completed or terminated interventional studies of FDA-regulated products, 5 (63%) have results posted.
First submitted before Principia Biopharma became part of Sanofi.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Washout period
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
In BT period, participants received placebo orally twice daily (BID) up to 37 weeks along with sponsor-provided corticosteroids (CS). After at least two weeks of control of disease activity (CDA; no new lesions and established lesions begin to heal), based on protocol-specified clinical criteria, investigators could decrease the CS dose to a minimum of 5 milligrams (mg) prednisone/prednisolone per day from Week 29 to Week 37. Post completion of BT period, eligible participants received rilzabrutinib 400 mg BID up to Week 61 in OLE period and those who were eligible after OLE period completion, continued the same treatment until Week 109 in LTE period according to protocol-specified criteria.
Drug: Rilzabrutinib · Drug: Placebo
In BT period, participants received rilzabrutinib 400 mg orally BID up to 37 weeks along with sponsor-provided CS. After at least two weeks of CDA (no new lesions and established lesions begin to heal), based on protocol-specified clinical criteria, investigators could decrease the CS dose to a minimum of 5 mg prednisone/prednisolone per day from Week 29 to Week 37. Post completion of BT period, eligible participants received rilzabrutinib 400 mg BID up to Week 61 in OLE period and those who were eligible after OLE period completion, continued the same treatment until Week 109 in LTE period according to protocol-specified criteria.
Drug: Rilzabrutinib
Pharmaceutical form: Tablet Route of administration: Oral
Pharmaceutical form: Tablet Route of administration: Oral
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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)
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)
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)
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)
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
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
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)
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)
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
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
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
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
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)
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
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
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
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).
| Milestone | Placebo Then Rilzabrutinib | Rilzabrutinib Then Rilzabrutinib |
|---|---|---|
| Started | 66 | 65 |
| Completed | 51 | 62 |
| Not completed | 15 | 3 |
| Withdrew: Adverse event | 7 | 2 |
| Withdrew: Lack of efficacy | 1 | 0 |
| Withdrew: Physician decision | 1 | 0 |
| Withdrew: Required prohibited medication | 2 | 0 |
| Withdrew: Withdrawal by subject | 4 | 0 |
| Withdrew: Other | 0 | 1 |
| Milestone | Placebo Then Rilzabrutinib | Rilzabrutinib Then Rilzabrutinib |
|---|---|---|
| Started | 51 | 61 |
| Completed | 35 | 45 |
| Not completed | 16 | 16 |
| Withdrew: Adverse event | 1 | 2 |
| Withdrew: Lack of efficacy | 3 | 2 |
| Withdrew: Non-compliance with study drug | 1 | 0 |
| Withdrew: Study terminated by sponsor | 8 | 10 |
| Withdrew: Withdrawal by subject | 3 | 2 |
| Milestone | Placebo Then Rilzabrutinib | Rilzabrutinib Then Rilzabrutinib |
|---|---|---|
| Started | 35 | 34 |
| Completed | 6 | 6 |
| Not completed | 29 | 28 |
| Withdrew: Lack of efficacy | 0 | 1 |
| Withdrew: Study terminated by sponsor | 28 | 25 |
| Withdrew: Withdrawal by subject | 0 | 2 |
| Withdrew: Other | 1 | 0 |
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 | Placebo Then Rilzabrutinib | 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 | 18.2 | 24.1 |
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.
| percentage of participants | Placebo Then Rilzabrutinib | 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 | 18.2 | 26.2 |
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.
| milligrams | Placebo Then Rilzabrutinib | Rilzabrutinib Then Rilzabrutinib |
|---|---|---|
| Cumulative Oral Corticosteroid Dose From Baseline to Week 37: PV mITT Population | 5653.2 ± 3155.97 | 5131.4 ± 2623.92 |
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.
| milligrams | Placebo Then Rilzabrutinib | Rilzabrutinib Then Rilzabrutinib |
|---|---|---|
| Cumulative Oral Corticosteroid Dose From Baseline to Week 37: mITT Population | 5392.2 ± 2993.02 | 4860.2 ± 2545.32 |
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".
| days | Placebo Then Rilzabrutinib | Rilzabrutinib Then Rilzabrutinib |
|---|---|---|
| Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: PV mITT Population | 34.1 ± 51.58 | 50.5 ± 67.10 |
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".
| days | Placebo Then Rilzabrutinib | Rilzabrutinib Then Rilzabrutinib |
|---|---|---|
| Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: mITT Population | 34.0 ± 54.36 | 54.3 ± 68.76 |
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.
| days | Placebo Then Rilzabrutinib | Rilzabrutinib Then Rilzabrutinib |
|---|---|---|
| Time to First Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: PV mITT Population | 252.0 (150.00 to NA) | 197.0 (156.00 to NA) |
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.
| days | Placebo Then Rilzabrutinib | Rilzabrutinib Then Rilzabrutinib |
|---|---|---|
| Time to First Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: mITT Population | NA (NA to NA) | 197.0 (142.00 to NA) |
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 | Placebo Then Rilzabrutinib | 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 | 10.9 | 24.1 |
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 | Placebo Then Rilzabrutinib | 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 | 12.1 | 26.2 |
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 | Placebo Then Rilzabrutinib | 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 | 29.1 | 35.2 |
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 | Placebo Then Rilzabrutinib | 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 | 27.3 | 38.5 |
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".
| days | Placebo Then Rilzabrutinib | Rilzabrutinib Then Rilzabrutinib |
|---|---|---|
| Baseline to Week 61 | 73.8 ± 95.35 | 112.2 ± 120.65 |
| Baseline to Week 109 | 102.2 ± 133.22 | 157.0 ± 179.71 |
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".
| days | Placebo Then Rilzabrutinib | Rilzabrutinib Then Rilzabrutinib |
|---|---|---|
| Baseline to Week 61 | 78.1 ± 98.68 | 120.4 ± 124.38 |
| Baseline to Week 109 | 124.6 ± 153.76 | 171.6 ± 186.66 |
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".
| days | Placebo Then Rilzabrutinib | Rilzabrutinib Then Rilzabrutinib |
|---|---|---|
| Baseline to Week 61 | 13.5 ± 35.33 | 28.6 ± 52.33 |
| Baseline to Week 109 | 28.4 ± 77.54 | 60.7 ± 118.87 |
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".
| days | Placebo Then Rilzabrutinib | Rilzabrutinib Then Rilzabrutinib |
|---|---|---|
| Baseline to Week 61 | 17.6 ± 38.56 | 33.5 ± 55.06 |
| Baseline to Week 109 | 49.5 ± 106.14 | 72.5 ± 125.60 |
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.
| units on a scale | Placebo Then Rilzabrutinib | Rilzabrutinib Then Rilzabrutinib |
|---|---|---|
| CWS | 54.46 ± 8.136 | 73.60 ± 7.397 |
| AIS | 9.42 ± 6.516 | 19.95 ± 5.924 |
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.
| units on a scale | Placebo Then Rilzabrutinib | Rilzabrutinib Then Rilzabrutinib |
|---|---|---|
| CWS | 51.68 ± 7.368 | 68.15 ± 6.732 |
| AIS | 8.63 ± 5.730 | 18.23 ± 5.236 |
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.
| units on a scale | Placebo Then Rilzabrutinib | Rilzabrutinib Then Rilzabrutinib |
|---|---|---|
| Week 5 | -7.567 ± 12.6310 | -7.224 ± 6.9832 |
| Week 13 | -11.076 ± 11.4549 | -13.925 ± 10.1497 |
| Week 25 | -11.333 ± 13.8064 | -15.292 ± 10.5552 |
| Week 37 | -13.000 ± 10.9202 | -14.167 ± 9.8679 |
| Week 61 | -12.900 ± 6.6418 | -16.475 ± 10.1585 |
| Week 109 | -21.300 | -18.250 ± 9.8288 |
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.
| units on a scale | Placebo Then Rilzabrutinib | Rilzabrutinib Then Rilzabrutinib |
|---|---|---|
| Week 5 | -7.870 ± 12.5361 | -7.161 ± 6.5918 |
| Week 13 | -11.253 ± 12.1328 | -13.139 ± 10.3317 |
| Week 25 | -11.722 ± 13.2580 | -14.174 ± 11.1997 |
| Week 37 | -12.918 ± 11.0260 | -13.442 ± 10.2669 |
| Week 61 | -13.793 ± 8.9794 | -14.649 ± 11.4991 |
| Week 109 | -23.967 ± 16.4628 | -18.250 ± 9.8288 |
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.
| score on a scale | Placebo Then Rilzabrutinib | Rilzabrutinib Then Rilzabrutinib |
|---|---|---|
| Week 5 | -2.20 ± 6.856 | -4.47 ± 7.668 |
| Week 13 | -4.04 ± 6.831 | -6.22 ± 7.218 |
| Week 25 | -5.88 ± 7.443 | -8.32 ± 7.647 |
| Week 37 | -4.53 ± 7.518 | -7.19 ± 8.187 |
| Week 61 | -7.76 ± 6.389 | -8.64 ± 10.140 |
| Week 109 | -19.00 | -19.50 ± 6.364 |
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.
| score on a scale | Placebo Then Rilzabrutinib | Rilzabrutinib Then Rilzabrutinib |
|---|---|---|
| Week 5 | -2.02 ± 6.474 | -4.50 ± 7.324 |
| Week 13 | -3.18 ± 7.262 | -5.93 ± 7.168 |
| Week 25 | -5.23 ± 7.259 | -7.57 ± 7.667 |
| Week 37 | -4.43 ± 7.150 | -7.00 ± 7.843 |
| Week 61 | -7.40 ± 7.416 | -7.47 ± 9.263 |
| Week 109 | -13.00 ± 6.000 | -19.50 ± 6.364 |
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 | Placebo Then Rilzabrutinib | Rilzabrutinib Then Rilzabrutinib |
|---|---|---|
| Week 5 | 0.0 | 2.0 |
| Week 13 | 2.1 | 4.0 |
| Week 25 | 4.4 | 4.2 |
| Week 37 | 7.9 | 4.2 |
| Week 61 | 11.8 | 12.0 |
| Week 109 | 0.0 | 50.0 |
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 | Placebo Then Rilzabrutinib | Rilzabrutinib Then Rilzabrutinib |
|---|---|---|
| Week 5 | 0.0 | 1.7 |
| Week 13 | 1.8 | 5.0 |
| Week 25 | 3.7 | 6.8 |
| Week 37 | 6.4 | 5.1 |
| Week 61 | 12.0 | 8.3 |
| Week 109 | 33.3 | 50.0 |
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.
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
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".
No measurements were reported for this outcome.
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.
| relapses | Placebo Then Rilzabrutinib | Rilzabrutinib Then Rilzabrutinib |
|---|---|---|
| Total Number of Disease Relapses/Flares From Initial Control of Disease Activity (CDA) to Week 37: PV mITT Population | 0.6 ± 0.96 | 0.3 ± 0.55 |
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.
| relapses | Placebo Then Rilzabrutinib | Rilzabrutinib Then Rilzabrutinib |
|---|---|---|
| Total Number of Disease Relapses/Flares From Initial Control of Disease Activity to Week 37: mITT Population | 0.6 ± 0.94 | 0.3 ± 0.54 |
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.
| days | Placebo Then Rilzabrutinib | Rilzabrutinib Then Rilzabrutinib |
|---|---|---|
| Time to Initial Relapse/Flare From Initial Control of Disease Activity to Week 37: PV mITT Population | 243.0 (144.00 to NA) | NA (NA to NA) |
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.
| days | Placebo Then Rilzabrutinib | Rilzabrutinib Then Rilzabrutinib |
|---|---|---|
| Time to Initial Relapse/Flare From Initial Control of Disease Activity to Week 37: mITT Population | 243.0 (148.00 to NA) | NA (NA to NA) |
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 | Placebo Then Rilzabrutinib | 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 | 58.2 | 35.2 |
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 | Placebo Then Rilzabrutinib | 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 | 59.1 | 36.9 |
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 | Placebo Then Rilzabrutinib | 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 | 43.1 | 28.3 |
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 | Placebo Then Rilzabrutinib | Rilzabrutinib 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 | 29.7 |
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".
| days | Placebo Then Rilzabrutinib | Rilzabrutinib 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 ± 59.01 | 62.5 ± 67.59 |
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".
| days | Placebo Then Rilzabrutinib | Rilzabrutinib Then Rilzabrutinib |
|---|---|---|
| Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Week 37 to Week 61: mITT Population | 57.1 ± 59.99 | 67.1 ± 68.03 |
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".
| days | Placebo Then Rilzabrutinib | Rilzabrutinib 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 ± 39.60 | 30.5 ± 53.92 |
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".
| days | Placebo Then Rilzabrutinib | Rilzabrutinib Then Rilzabrutinib |
|---|---|---|
| Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Week 37 to Week 61: mITT Population | 22.8 ± 42.58 | 35.3 ± 56.32 |
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.
| Participants | BT Period: Placebo | BT Period: Rilzabrutinib | OLE Period: Placebo Then Rilzabrutinib | OLE Period: Rilzabrutinib Then Rilzabrutinib | LTE Period: Placebo Then Rilzabrutinib | LTE Period: Rilzabrutinib Then Rilzabrutinib |
|---|---|---|---|---|---|---|
| TEAE | 54 | 55 | 33 | 35 | 18 | 14 |
| TESAE | 10 | 6 | 4 | 0 | 1 | 2 |
Data for this OM was not planned to be collected and analyzed for placebo arm of the study.
| nanograms per milliliter | Rilzabrutinib |
|---|---|
| Day 1: pre-dose | NA ± NA |
| Day 1: 2-hour post-dose | 273.13 ± 264.136 |
Anti-dsg1 and anti-dsg3 autoantibody levels was assessed by enzyme-linked immunosorbent assay (ELISA) method.
| units/milliliter | Placebo | Rilzabrutinib |
|---|---|---|
| Baseline: Anti-dsg1 | 108.4 ± 288.97 | 85.9 ± 139.17 |
| Baseline: Anti-dsg3 | 392.5 ± 697.52 | 464.1 ± 668.22 |
| Change at Week 13: Anti-dsg1 | 60.6 ± 116.32 | 15.4 ± 34.20 |
| Change at Week 13: Anti-dsg3 | 197.1 ± 320.37 | 99.8 ± 146.65 |
| Change at Week 25: Anti-dsg1 | 48.2 ± 93.15 | 17.5 ± 37.44 |
| Change at Week 25: Anti-dsg3 | 218.6 ± 314.74 | 153.7 ± 351.56 |
| Change at Week 37: Anti-dsg1 | 42.0 ± 95.02 | 24.1 ± 60.01 |
| Change at Week 37: Anti-dsg3 | 204.4 ± 313.26 | 213.9 ± 389.85 |
| Change at Week 49: Anti-dsg1 | 12.1 ± 18.66 | 17.1 ± 31.99 |
| Change at Week 49: Anti-dsg3 | 215.6 ± 327.22 | 277.1 ± 575.77 |
| Change at Week 61: Anti-dsg1 | 12.0 ± 20.61 | 12.5 ± 26.08 |
| Change at Week 61: Anti-dsg3 | 252.3 ± 439.45 | 223.5 ± 271.69 |
| Change at Week 73: Anti-dsg1 | 12.8 ± 23.21 | 10.5 ± 26.34 |
| Change at Week 73: Anti-dsg3 | 237.1 ± 412.33 | 157.6 ± 186.82 |
| Change at Week 85: Anti-dsg1 | 11.7 ± 24.31 | 14.2 ± 28.05 |
| Change at Week 85: Anti-dsg3 | 169.9 ± 349.29 | 132.4 ± 189.76 |
| Change at Week 97: Anti-dsg1 | 3.6 ± 5.27 | 4.7 ± 8.60 |
| Change at Week 97: Anti-dsg3 | 193.0 ± 330.12 | 95.4 ± 180.66 |
| Change at Week 109: Anti-dsg1 | 1.0 | 2.0 ± 0.0 |
| Change at Week 109: Anti-dsg3 | 0.0 | 94.0 ± 115.97 |
Anti-dsg1 and anti-dsg3 autoantibody levels was assessed by ELISA method.
| units/milliliter | Placebo | Rilzabrutinib |
|---|---|---|
| Baseline: Anti-dsg1 | 132.2 ± 275.92 | 141.7 ± 366.74 |
| Baseline: Anti-dsg3 | 328.8 ± 651.84 | 385.8 ± 632.71 |
| Change at Week 13: Anti-dsg1 | 73.7 ± 116.08 | 39.8 ± 102.35 |
| Change at Week 13: Anti-dsg3 | 166.1 ± 302.25 | 82.5 ± 138.29 |
| Change at Week 25: Anti-dsg1 | 65.6 ± 105.99 | 40.5 ± 106.10 |
| Change at Week 25: Anti-dsg3 | 182.4 ± 298.18 | 124.3 ± 320.96 |
| Change at Week 37: Anti-dsg1 | 59.5 ± 101.58 | 37.0 ± 68.28 |
| Change at Week 37: Anti-dsg3 | 167.8 ± 293.78 | 176.5 ± 362.67 |
| Change at Week 49: Anti-dsg1 | 31.9 ± 53.27 | 44.1 ± 102.07 |
| Change at Week 49: Anti-dsg3 | 163.4 ± 298.38 | 216.4 ± 520.01 |
| Change at Week 61: Anti-dsg1 | 41.5 ± 68.66 | 44.6 ± 88.74 |
| Change at Week 61: Anti-dsg3 | 165.3 ± 372.10 | 159.2 ± 249.62 |
| Change at Week 73: Anti-dsg1 | 43.5 ± 87.58 | 48.5 ± 139.91 |
| Change at Week 73: Anti-dsg3 | 165.2 ± 358.15 | 112.0 ± 171.90 |
| Change at Week 85: Anti-dsg1 | 22.3 ± 39.62 | 42.1 ± 105.90 |
| Change at Week 85: Anti-dsg3 | 116.9 ± 296.51 | 97.9 ± 170.97 |
| Change at Week 97: Anti-dsg1 | 21.9 ± 46.36 | 52.2 ± 141.86 |
| Change at Week 97: Anti-dsg3 | 107.6 ± 254.47 | 76.0 ± 161.13 |
| Change at Week 109: Anti-dsg1 | 4.7 ± 4.73 | 2.0 ± 0.00 |
| Change at Week 109: Anti-dsg3 | 1.0 ± 1.73 | 94.0 ± 115.97 |
Collected over 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). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| BT Period: Placebo | 2/66 (3%) | 10/66 (15.2%) | 41/66 (62.1%) |
| BT Period: Rilzabrutinib | 0/65 (0%) | 6/65 (9.2%) | 47/65 (72.3%) |
| OLE Period: Placebo Then Rilzabrutinib | 0/51 (0%) | 4/51 (7.8%) | 18/51 (35.3%) |
| OLE Period: Rilzabrutinib Then Rilzabrutinib | 0/61 (0%) | 0/61 (0%) | 22/61 (36.1%) |
| OLE Period: Overall (All Participants) | 0/112 (0%) | 4/112 (3.6%) | 40/112 (35.7%) |
| LTE Period: Placebo Then Rilzabrutinib | 0/35 (0%) | 1/35 (2.9%) | 11/35 (31.4%) |
| LTE Period: Rilzabrutinib Then Rilzabrutinib | 0/34 (0%) | 2/34 (5.9%) | 7/34 (20.6%) |
| LTE Period: Overall (All Participants) | 0/69 (0%) | 3/69 (4.3%) | 18/69 (26.1%) |
| Event | BT Period: Placebo | BT Period: Rilzabrutinib | OLE Period: Placebo Then Rilzabrutinib | OLE Period: Rilzabrutinib Then Rilzabrutinib | OLE Period: Overall (All Participants) | LTE Period: Placebo Then Rilzabrutinib | LTE Period: Rilzabrutinib Then Rilzabrutinib | LTE Period: Overall (All Participants) |
|---|---|---|---|---|---|---|---|---|
| Covid-19Infections and infestations | 2/66 | 0/65 | 1/51 | 0/61 | 1/112 | 1/35 | 1/34 | 2/69 |
| PemphigusSkin and subcutaneous tissue disorders | 2/66 | 0/65 | 0/51 | 0/61 | 0/112 | 0/35 | 0/34 | 0/69 |
| Vogt-Koyanagi-Harada DiseaseEye disorders | 0/66 | 0/65 | 0/51 | 0/61 | 0/112 | 0/35 | 1/34 | 1/69 |
| Covid-19 PneumoniaInfections and infestations | 1/66 | 1/65 | 1/51 | 0/61 | 1/112 | 0/35 | 0/34 | 0/69 |
| Renal NeoplasmNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/66 | 0/65 | 1/51 | 0/61 | 1/112 | 0/35 | 0/34 | 0/69 |
| Embolism ArterialVascular disorders | 0/66 | 0/65 | 1/51 | 0/61 | 1/112 | 0/35 | 0/34 | 0/69 |
| Meningitis BacterialInfections and infestations | 0/66 | 1/65 | 0/51 | 0/61 | 0/112 | 0/35 | 0/34 | 0/69 |
| Septic ShockInfections and infestations | 0/66 | 1/65 | 0/51 | 0/61 | 0/112 | 0/35 | 0/34 | 0/69 |
| PresyncopeNervous system disorders | 0/66 | 1/65 | 0/51 | 0/61 | 0/112 | 0/35 | 0/34 | 0/69 |
| Cardiac ArrestCardiac disorders | 0/66 | 1/65 | 0/51 | 0/61 | 0/112 | 0/35 | 0/34 | 0/69 |
| Event | BT Period: Placebo | BT Period: Rilzabrutinib | OLE Period: Placebo Then Rilzabrutinib | OLE Period: Rilzabrutinib Then Rilzabrutinib | OLE Period: Overall (All Participants) | LTE Period: Placebo Then Rilzabrutinib | LTE Period: Rilzabrutinib Then Rilzabrutinib | LTE Period: Overall (All Participants) |
|---|---|---|---|---|---|---|---|---|
| Increased Tendency To BruiseBlood and lymphatic system disorders | 7/66 | 16/65 | 2/51 | 3/61 | 5/112 | 1/35 | 0/34 | 1/69 |
| MyopathyMusculoskeletal and connective tissue disorders | 10/66 | 15/65 | 1/51 | 2/61 | 3/112 | 0/35 | 1/34 | 1/69 |
| InsomniaPsychiatric disorders | 6/66 | 12/65 | 2/51 | 1/61 | 3/112 | 0/35 | 0/34 | 0/69 |
| DepressionPsychiatric disorders | 6/66 | 11/65 | 1/51 | 2/61 | 3/112 | 0/35 | 0/34 | 0/69 |
| NauseaGastrointestinal disorders | 3/66 | 8/65 | 8/51 | 2/61 | 10/112 | 0/35 | 0/34 | 0/69 |
| HeadacheNervous system disorders | 5/66 | 9/65 | 2/51 | 3/61 | 5/112 | 1/35 | 1/34 | 2/69 |
| Dermatitis AcneiformSkin and subcutaneous tissue disorders | 3/66 | 9/65 | 1/51 | 2/61 | 3/112 | 2/35 | 0/34 | 2/69 |
| DiarrhoeaGastrointestinal disorders | 7/66 | 8/65 | 4/51 | 3/61 | 7/112 | 0/35 | 0/34 | 0/69 |
| HypertensionVascular disorders | 7/66 | 5/65 | 0/51 | 2/61 | 2/112 | 1/35 | 0/34 | 1/69 |
| ManiaPsychiatric disorders | 3/66 | 6/65 | 0/51 | 0/61 | 0/112 | 0/35 | 0/34 | 0/69 |
Analysis was performed on randomized population.
| Age, Continuous(years) | Placebo Then Rilzabrutinib | Rilzabrutinib Then Rilzabrutinib | Total |
|---|---|---|---|
| Mean | 52.9 ± 14.00 | 50.5 ± 14.11 | 51.7 ± 14.05 |
| Sex: Female, Male(Participants) | Placebo Then Rilzabrutinib | Rilzabrutinib Then Rilzabrutinib | Total |
|---|---|---|---|
| Female | 34 | 36 | 70 |
| Male | 32 | 29 | 61 |
| Race (NIH/OMB)(Participants) | Placebo Then Rilzabrutinib | Rilzabrutinib Then Rilzabrutinib | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 4 | 2 | 6 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 3 | 1 | 4 |
| White | 52 | 58 | 110 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 7 | 4 | 11 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
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Studies of the drug tested here: Rilzabrutinib
Principia Biopharma, a Sanofi Company →