This is a Phase III, randomized, double-blind, double-dummy, active-comparator, parallel-arm, multicenter study to evaluate the efficacy and safety of rituximab compared with MMF in participants with moderate-to-severely active PV requiring 60-120 milligrams per day (mg/day) oral prednisone or equivalent. Participants must have a confirmed diagnosis of PV within the previous 24 months (by skin or mucosal biopsy and immunohistochemistry) and evidence of active disease at screening. Approximately 135 participants will be enrolled at up to 60 centers worldwide. Participants will be randomized in a 1:1 ratio to receive either rituximab plus MMF placebo or rituximab placebo plus MMF. Randomization will be stratified by duration of illness. The study will consist of three periods: a screening period of up to 28 days, a 52-week double-blind treatment period, and a 48-week safety follow up period that begins at the time of study treatment completion or discontinuation.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
135
MMF matching placebo will be administered orally Q12H.
MMF will be administered at a starting dose of 500 milligrams (mg) Q12H and the dose will be titrated to achieve a goal of 1 gram (gm) Q12H.
Rituximab will be administered at a dose of 1000 mg via IV infusion.
Rituximab matching placebo will be administered via IV infusion.
University of Alabama Birmingham
Birmingham, Alabama, United States
University of Arizona Medical Research Office
Tucson, Arizona, United States
UC Davis Department of Dermatology
Sacramento, California, United States
Univ of Calif-San Francisco
San Francisco, California, United States
Los Angeles Biomedical Research Institute
Torrance, California, United States
Percentage of Participants (Excluding Telemedicine [TM] Participants) Who Achieved Sustained Complete Remission, Evaluated by the Pemphigus Disease Area Index (PDAI) Activity Score
Time frame: From Baseline up to 52 Weeks (up to clinical cut-off date (CCOD) of 28 November 2018)
Cumulative Oral Corticosteroid Dose
Time frame: From Baseline up to 52 Weeks (up to CCOD of 28 November 2018)
Total Number of Protocol Defined Disease Flares
Disease flare is defined as appearance of three or more new lesions a month that do not heal spontaneously within 1 week, or by the extension of established lesions, in a participant who has achieved disease control.
Time frame: From Baseline up to 52 Weeks (up to CCOD of 28 November 2018)
Time to Initial Sustained Complete Remission
Time frame: From Baseline up to 52 Weeks (up to CCOD of 28 November 2018)
Time to Protocol Defined Disease Flare
Disease flare is defined as the appearance of three or more new lesions a month that do not heal spontaneously within 1 week or by the extension of established lesions in a participant who has achieved disease control.
Time frame: From Baseline up to 52 Weeks (up to CCOD of 28 November 2018)
Change in Health-Related Quality of Life (HRQoL), as Measured by the Dermatology Life Quality Index (DLQI) Score
Total DLQI scores range from 0 to 30 with higher DLQI scores reflecting greater impairment in a participant's health-related quality of life. The DLQI score is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. The measure type mean is the estimated mean from adjusted MMRM.
Time frame: From Baseline up to 52 Weeks (up to CCOD of 28 November 2018)
Percentage of Participants With Adverse Events, Serious Adverse Events, and Corticosteroid-Related Adverse Events
An adverse event is any untoward medical occurrence in a participant to whom a medicinal product is administered and which does not necessarily have a causal relationship with this treatment. A serious adverse event is an adverse event that results in death or is life-threatening or requires/prolongs hospitalization or results in persistent/significant disability/incapacity or congenital abnormality/birth defect. Adverse events of Grade 3 of higher are severe and life-threatening adverse events CS-related adverse events - causality as determined by the investigator.
Time frame: Baseline up to 52 Weeks (up to CCOD of 28 November 2018)
Percentage of Participants With Anti-Drug Antibodies (ADA)
Participants with treatment-induced and treatment-enhanced anti-drug antibodies. The clinical relevance of anti-rituximab antibody formation in RITUXAN treated pemphigus vulgaris (PV) participants is unclear.
Time frame: Baseline up to 52 Weeks (up to CCOD of 28 November 2018)
Percentage of Participants With Immunoglobulin (Ig) Levels Below Lower Limit of Normal (LLN)
Time frame: Baseline; Weeks 16, 24, 40 and 52; (end of treatment: up to Week 52) (up to CCOD of 28 November 2018)
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Northwestern University
Chicago, Illinois, United States
Massachusetts General Hospital Dermatology
Boston, Massachusetts, United States
University of Minnesota
Minneapolis, Minnesota, United States
St Louis University Hospital
St Louis, Missouri, United States
Uni of NY and Roswell Cancer
Buffalo, New York, United States
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