A Study to Evaluate the Efficacy and Safety of Rituximab Versus Mycophenolate Mofetil (MMF) in Participants With Pemphigus Vulgaris (PV)
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|ClinicalTrials.gov Identifier: NCT02383589|
Recruitment Status : Completed
First Posted : March 9, 2015
Results First Posted : January 18, 2020
Last Update Posted : November 10, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Pemphigus Vulgaris||Drug: Mycophenolate Mofetil Placebo Drug: Mycophenolate Mofetil Drug: Rituximab Drug: Rituximab Placebo||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||135 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||A Randomized, Double-Blind, Double-Dummy, Active-Comparator, Multicenter Study to Evaluate the Efficacy and Safety of Rituximab Versus MMF in Patients With Pemphigus Vulgaris|
|Actual Study Start Date :||May 26, 2015|
|Actual Primary Completion Date :||November 28, 2018|
|Actual Study Completion Date :||October 29, 2019|
Active Comparator: Mycophenolate Mofetil (MMF)
Participants will receive MMF orally twice daily (every 12 hours, Q12H) from Day 1 to Week 52. Participants will also receive rituximab matching placebo by intravenous (IV) infusion on Days 1 and 15 with repeat administration on Days 168 and 182 provided specific safety criteria have been met.
Drug: Mycophenolate Mofetil
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.
Other Name: MMF, CellCept
Drug: Rituximab Placebo
Rituximab matching placebo will be administered via IV infusion.
Other Name: MabThera/Rituxan
Experimental: Rituximab (RTX)
Participants will receive rituximab by IV infusion on Days 1 and 15 with repeat administration on Days 168 and 182 provided specific safety criteria have been met. Participants will also receive MMF matching placebo orally twice daily Q12H from Day 1 to Week 52.
Drug: Mycophenolate Mofetil Placebo
MMF matching placebo will be administered orally Q12H.
Rituximab will be administered at a dose of 1000 mg via IV infusion.
Other Name: MabThera/Rituxan
- 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 [ Time Frame: From Baseline up to 52 Weeks (up to CCOD of 28 November 2018) ]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 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 [ Time Frame: From Baseline up to 52 Weeks (up to CCOD of 28 November 2018) ]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.
- Change in Health-Related Quality of Life (HRQoL), as Measured by the Dermatology Life Quality Index (DLQI) Score [ Time Frame: From Baseline up to 52 Weeks (up to CCOD of 28 November 2018) ]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.
- Percentage of Participants With Adverse Events, Serious Adverse Events, and Corticosteroid-Related Adverse Events [ Time Frame: Baseline up to 52 Weeks (up to CCOD of 28 November 2018) ]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.
- Percentage of Participants With Anti-Drug Antibodies (ADA) [ Time Frame: Baseline up to 52 Weeks (up to CCOD of 28 November 2018) ]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.
- 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) ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02383589
|Study Director:||Clinical Trials||Hoffmann-La Roche|