A Study of PRN1008 in Patients With Pemphigus

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.

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

Cumulative 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 (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 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 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.

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.

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.

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.

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 (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 (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 (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 (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".

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 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 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 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 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 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 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 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.

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.

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 (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 (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 (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 (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".

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.

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

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

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