Trial record 1 of 1 for:    rituxan pemphigus vulgaris
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A Randomized, Double-Blind Study to Evaluate the Efficacy and Safety of Rituximab Versus MMF in Patients With Pemphigus Vulgaris

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2016 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: October 3, 2016
Last verified: October 2016
  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 mycophenolate mofetil (MMF) in patients with moderate-to-severely active pemphigus vulgaris (PV) requiring 60-120 mg/day oral prednisone (or equivalent). Patients 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 patients will be enrolled at up to 60 centers worldwide. Patients 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 (PV)
Other: MMF placebo
Drug: mycophenolate mofetil
Drug: rituximab [MabThera/Rituxan]
Other: rituximab placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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:
  • Proportion of pts who achieve a sustained complete remission (wound healing with no new active lesions on 0 mg prednisone [equivalent]/day and maintaining response >/=16 consecutive weeks) without experiencing an event that constitutes treatment failure [ Time Frame: 52 weeks ]

Secondary Outcome Measures:
  • Change in patients' impression of PV symptoms as measured by the Patients' Global Impression of Change (PGIC) score [ Time Frame: From baseline to Week 52 ]
  • Change in clinician impression of patients' PV symptoms, as measured by the Clinician Global Impression of Change (CGIC) score [ Time Frame: From baseline to Week 52 ]
  • Time to flare (relapse) [ Time Frame: 52 weeks ]
  • Cumulative oral corticosteroid dose over the treatment period [ Time Frame: 52 weeks ]
  • Duration of sustained complete remission [ Time Frame: 52 weeks ]
  • Total number of disease flares during the treatment period [ Time Frame: 52 weeks ]
  • Change in health-related quality of life (HRQoL), as measured by the Dermatology Life Quality Index (DLQI) score [ Time Frame: From baseline to Week 52 ]
  • Time to initial sustained complete remission [ Time Frame: 52 weeks ]

Estimated Enrollment: 124
Study Start Date: May 2015
Estimated Study Completion Date: May 2019
Estimated Primary Completion Date: May 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: MMF Drug: mycophenolate mofetil
1 g will be given orally in divided doses at start. Dose wil be increased gradually to 1 g twice daily.
Other: rituximab placebo
Matching rituximab placebo given intravenously on Day 1 and 15, with repeat matching placebo administration on Day 168 and 182 provided specific safety criteria have been met
Experimental: MabThera/Rituxan (rituximab) Other: MMF placebo
Divided dose given orally daily
Drug: rituximab [MabThera/Rituxan]
1000 mg rituximab given by intravenous infusion on Day 1 and 15, with repeat rituximab administration on Day 168 and 182 provided specific safety criteria have been met

  Eligibility

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

Inclusion Criteria:

  • Age 18-75 years
  • Signed Informed Consent Form
  • Confirmed diagnosis of PV within the previous 24 months, based on the presence of the following: histological features of acantholysis via skin or mucosal biopsy and tissue bound IgG antibodies by direct immunofluorescence on the surface of affected epithelium
  • Presence of moderate-to-severely active disease, defined as at least 6 lesions that last more than 1 week or at least 3% body surface involvement, including cutaneous and/or mucosal lesions
  • Mucosal or cutaneous Pemphigus Disease Area Index (PDAI) activity score of 3 and overall PDAI activity score of 15-45 (moderate-to-severely active disease)
  • 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 adequate methods of contraception, including at least one method with a failure rate of less than 1% 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 patient. 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 less than 1% per year include tubal ligation, male sterilization, hormonal implants, established, proper use of combined oral or injected hormonal contraceptives, and certain intrauterine devices.

  • For men: 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 patient.

Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.

  • 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 a negative result from a serum pregnancy test or a urine pregnancy test with a sensitivity of >/=50 mU/mL within 1 week 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 patient 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) 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-CD20, anti CD22, or anti-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 patient'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.rochegenentechtrials@roche.com

  Show 69 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 
Study First Received: March 4, 2015
Last Updated: October 3, 2016

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 January 23, 2017