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Trial record 1 of 1 for:    rituxan pemphigus vulgaris
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A Study to Evaluate the Efficacy and Safety of Rituximab Versus Mycophenolate Mofetil (MMF) in Participants With Pemphigus Vulgaris (PV)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2017 by Hoffmann-La Roche
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02383589
First received: March 4, 2015
Last updated: March 16, 2017
Last verified: March 2017
  Purpose

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 124 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 Intervention Phase
Pemphigus Vulgaris
Drug: Mycophenolate Mofetil Placebo
Drug: Mycophenolate Mofetil
Drug: Rituximab
Drug: Rituximab Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Investigator
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants Who Achieve Sustained Complete Remission, Evaluated by the Pemphigus Disease Area Index (PDAI) Activity Score [ Time Frame: From baseline up to 52 weeks ]

Secondary Outcome Measures:
  • Time to Protocol Defined Disease Flare [ Time Frame: From baseline up to 52 weeks ]
  • Cumulative Oral Corticosteroid Dose [ Time Frame: From baseline up to 52 weeks ]
  • Duration of Sustained Complete Remission, Evaluated by the PDAI Activity Score [ Time Frame: From baseline up to 52 weeks ]
  • Protocol Defined Disease Flares [ Time Frame: From baseline up to 52 weeks ]
  • Change in Health-Related Quality of Life (HRQoL), as Measured by the Dermatology Life Quality Index (DLQI) Score [ Time Frame: Baseline, Weeks 12, 24, 40, and 52 ]
  • Time to Initial Sustained Complete Remission, Evaluated by the PDAI Activity Score [ Time Frame: From baseline up to 52 weeks ]
  • Change in Participants Impression of PV Symptoms, as Measured by the Patients' Global Impression of Change (PGIC) Questionnaire Score [ Time Frame: Baseline, Weeks 12, 24, 40, and 52 ]
  • Change in Clinician Impression of Participant's PV Symptoms, as Measured by the Clinician Global Impression of Change (CGIC) Questionnaire Score [ Time Frame: Baseline, Weeks 12, 24, 40, and 52 ]
  • Percentage of Participants With Adverse Events, Serious Adverse Events, and Corticosteroid-Related Adverse Events [ Time Frame: Baseline up to 100 weeks ]
  • Percentage of Participants With Human Anti-Chimeric Antibody (HACA) [ Time Frame: Baseline; Weeks 24 and 52/early withdrawal; 48 weeks after end of treatment (end of treatment: up to Week 52) ]
  • Blood Lymphocyte Levels [ Time Frame: Baseline; Weeks 2, 4, 8, 16, 24, 26, 40 and 52; 12, 24, 36, 48 weeks after end of treatment (end of treatment: up to Week 52) ]
  • Plasma Immunoglobulin (Ig) Levels [ Time Frame: Baseline; Weeks 16, 24, 40 and 52; 12, 24, 36, 48 weeks after end of treatment (end of treatment: up to Week 52) ]

Estimated Enrollment: 124
Actual Study Start Date: May 31, 2015
Estimated Study Completion Date: September 7, 2019
Estimated Primary Completion Date: September 30, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A: Mycophenolate Mofetil
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: B: Rituximab
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 Q12H from Day 1 to Week 52.
Drug: Mycophenolate Mofetil Placebo
MMF matching placebo will be administered orally Q12H.
Drug: Rituximab
Rituximab will be administered at a dose of 1000 mg via IV infusion.
Other Name: MabThera/Rituxan

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of PV within the previous 24 months, based on the presence of histological features of acantholysis via skin or mucosal biopsy and one of the following: tissue bound immunoglobulin G (IgG) antibodies by direct immunofluorescence on the surface of affected epithelium or serological detection of serum desmoglein-3 (DSg3) autoantibodies against epithelial cell surface either by indirect immunofluorescence microscopy or by enzyme-linked immunosorbent assay
  • Presence of moderate-to-severely active disease, defined as overall PDAI activity score of greater than or equal to (>/=)15
  • Receiving standard-of-care corticosteroids consisting of 60-120 mg/day oral prednisone or equivalent and, in the judgment of the investigator, expected to benefit from the addition of immunosuppressive therapy
  • For women who are not postmenopausal (>/=12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use two effective methods of contraception, including at least one method with a failure rate of less than (<) 1 percent (%) per year, during the treatment period and for at least 12 months after the last dose of study treatment

Abstinence is acceptable only if it is in line with the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception

Barrier methods must always be supplemented with the use of a spermicide

Examples of contraceptive methods with a failure rate of < 1% per year (highly effective contraceptive methods) include tubal ligation, male sterilization, hormonal implants, established, proper use of combined oral or injected hormonal contraceptives, and certain intrauterine devices

  • For men (including those who have undergone a vasectomy): agreement to remain abstinent or use a condom during the treatment period and for at least 12 months after the last dose of study treatment and agreement to refrain from donating sperm during this same period

Abstinence is only acceptable if it is in line with the preferred and usual lifestyle of the participant

Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception. In addition to male contraception, agreement to advise female partners of childbearing potential to use highly effective contraception during the study and for at least 12 months after the last dose of study treatment

  • Agreement to avoid excessive exposure to sunlight during study participation
  • Able to comply with the study protocol, in the investigator's judgment

Exclusion Criteria:

  • Diagnosis of pemphigus foliaceus or evidence of paraneoplastic pemphigus or other non-PV autoimmune blistering disease
  • History of a severe allergic or anaphylactic reaction to humanized or murine monoclonal antibodies, or known hypersensitivity to any component of rituximab
  • Known hypersensitivity or contraindication to MMF, mycophenolic acid, polysorbate, or oral corticosteroids
  • Lack of peripheral venous access
  • Pregnant or lactating, or intending to become pregnant during the study

Women who are not postmenopausal (>/=12 months of non-therapy-induced amenorrhea) or surgically sterile must have two negative results with a sensitivity of >/=25 milli-international units per milliliter (mIU/mL): one from a serum pregnancy test at Day -8 to Day -10 of screening and another from a urine pregnancy test at Day 1 prior to randomization

  • Participated in another interventional clinical trial within 28 days prior to randomization
  • Use of any investigational agent within 28 days or 5 elimination half-lives prior to randomization (whichever is the longer)
  • Significant cardiovascular or pulmonary disease (including obstructive pulmonary disease)
  • Evidence of any new or uncontrolled concomitant disease that, in the investigator's judgment, would preclude participant participation, including but not limited to nervous system, renal, hepatic, endocrine, malignant, or gastrointestinal disorders
  • Any concomitant condition that required treatment with oral or systemic corticosteroids within 12 weeks prior to randomization
  • Treatment with intravenous (IV) immunoglobulin (Ig), plasmapheresis, or other similar procedure within 8 weeks prior to randomization
  • Treatment with immunosuppressive medications (e.g., azathioprine, MMF) within 1 week prior to randomization
  • Treatment with cyclophosphamide within 12 weeks prior to randomization
  • History of or currently active primary or secondary immunodeficiency, including known history of HIV infection and other severe immunodeficiency blood disorders
  • Known active infection of any kind (excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with IV anti-infectives within 4 weeks prior to screening, or completion of oral anti-infectives within 2 weeks prior to randomization; entry into this study may be reconsidered once the infection has fully resolved
  • History of or current cancer, including solid tumors, hematologic malignancies, and carcinoma in situ (except complete excision of basal cell of the skin and squamous cell carcinoma of the skin that have been treated or excised and cured)
  • Currently active alcohol or drug abuse, or history of alcohol or drug abuse within 24 weeks prior to screening
  • Major surgery within 4 weeks prior to randomization, excluding diagnostic surgery
  • Treatment with rituximab or a B cell-targeted therapy (e.g., anti-cluster of differentiation [CD] 20 [CD20], anti CD22, or anti-B-lymphocyte stimulator [BLyS]) within 12 months prior to randomization
  • Treatment with a live or attenuated vaccine within 28 days prior to randomization; it is recommended that a participant's vaccination record and the need for immunization prior to study entry be carefully investigated
  • Evidence of abnormal liver enzymes or hematology laboratory values
  • Positive test results for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C virus (HCV) serology at screening
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02383589

Contacts
Contact: Reference Study ID Number: WA29330 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

  Show 71 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Genentech, Inc.
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02383589     History of Changes
Other Study ID Numbers: WA29330
2014-000382-41 ( EudraCT Number )
Study First Received: March 4, 2015
Last Updated: March 16, 2017

Additional relevant MeSH terms:
Pemphigus
Rituximab
Skin Diseases, Vesiculobullous
Skin Diseases
Autoimmune Diseases
Immune System Diseases
Mycophenolic Acid
Mycophenolate mofetil
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on April 21, 2017