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Trial record 1 of 1 for:    NCT02383589
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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 : Active, not recruiting
First Posted : March 9, 2015
Last Update Posted : January 23, 2019
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (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
Actual Study Start Date : May 26, 2015
Actual Primary Completion Date : November 28, 2018
Estimated Study Completion Date : November 7, 2019


Arm Intervention/treatment
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




Primary Outcome Measures :
  1. Percentage of Participants (Excluding Telemedicine [TM] 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 :
  1. Time to Protocol Defined Disease Flare [ Time Frame: From baseline up to 52 weeks ]
  2. Cumulative Oral Corticosteroid Dose [ Time Frame: From baseline up to 52 weeks ]
  3. Duration of Sustained Complete Remission, Evaluated by the PDAI Activity Score [ Time Frame: From baseline up to 52 weeks ]
  4. Protocol Defined Disease Flares [ Time Frame: From baseline up to 52 weeks ]
  5. 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 ]
  6. Time to Initial Sustained Complete Remission, Evaluated by the PDAI Activity Score [ Time Frame: From baseline up to 52 weeks ]
  7. 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 ]
  8. 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 ]
  9. Percentage of Participants With Adverse Events, Serious Adverse Events, and Corticosteroid-Related Adverse Events [ Time Frame: Baseline up to 100 weeks ]
  10. 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) ]
  11. 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) ]
  12. 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) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
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

Information from the National Library of Medicine

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


  Hide Study Locations
Locations
United States, Alabama
University of Alabama Birmingham
Birmingham, Alabama, United States, 35294
United States, Arizona
University of Arizona Medical Research Office
Tucson, Arizona, United States, 85724
United States, California
UC Davis Department of Dermatology
Sacramento, California, United States, 95816
Univ of Calif-San Francisco
San Francisco, California, United States, 94115
Los Angeles Biomedical Research Institute
Torrance, California, United States, 90502
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
United States, Massachusetts
Massachusetts General Hospital Dermatology
Boston, Massachusetts, United States, 02114
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
St Louis University Hospital
Saint Louis, Missouri, United States, 63104
United States, New York
Uni of NY and Roswell Cancer
Buffalo, New York, United States, 14203
Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
United States, North Carolina
Wake Forest Baptist Hospital Center for Dermatology Research
Winston-Salem, North Carolina, United States, 27104
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
United States, Oregon
Oregon Health Sciences Uni
Portland, Oregon, United States, 97239
United States, Pennsylvania
Penn University
Philadelphia, Pennsylvania, United States, 19104
Argentina
Hospital Italiano
Buenos Aires, Argentina, C1181ACH
Centro de Investigaciones Médicas - CIM
Florencio Varela, Argentina, 1888
Hospital Luis Lagomaggiore
Mendoza, Argentina, 5500
Hospital Austral
Pilar, Pcia De Buenos Aires, Argentina, 1500
Australia, New South Wales
St George Hospital
Kogarah, New South Wales, New South Wales, Australia, 2217
Australia, Queensland
Veracity Clinical Research
Woolloongabba, Queensland, Australia, 4102
Brazil
Faculdade de Medicina de Botucatu - Hospital das Clínicas
Botucatu, SP, Brazil, 18618-970
Faculdade de Medicina da Universidade de São Paulo
Sao Paulo, SP, Brazil, 01246-903
Santa Casa de São Paulo Hospital Central
São Paulo, SP, Brazil, 01221-020
Canada, Alberta
University of Alberta
Edmonton, Alberta, Canada, T6G 2G3
Canada, British Columbia
Guildford Dermatology Specialists
Surrey, British Columbia, Canada, V3R 6A7
Canada, Ontario
Lynderm Research
Markham, Ontario, Canada, L3P 1X2
France
Department of Dermatology Avicenne Hospital & University
Bobigny, France, 93000
CHU Hopitaux de Bordeaux
CHU Hopitaux De Bordeaux, France, 33000
Centre Hospitalier Régional Universitaire de Lille (CHRU) - Hôpital Claude Huriez
Lille, France, 59037
Les Hospices Civils de Lyon Dermatologie inflammatoire et médecine interne
Lyon / Pierre Bénite, France, 69495
CHU de Reims
Reims, France, 51100
CHU de Rennes - Hopital de Pontchaillo
Rennes, France, 35033
CHU de Rouen - Hôpital Charles Nicolle
Rouen, France, 76031
CHU Saint Etienne - Hôpital Nord
Saint Etienne, France, 42055
Germany
University Hospital for Dermatology
Dresden, Germany, 01304
Kompetenzzentrum Fragile Haut Klinik fur Dermatologie und Venerologie
Freiburg, Germany, 79104
Universitätsklinikum Heidelberg
Heidelberg, Germany, 69120
Klinik und Poliklinik für Dermatologie und Venerologie Universitätsklinikum Köln
Koeln, Germany, 50937
University Hospital Schleswig-Holstein
Lübeck, Germany, 23538
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR, Hautklinik und Poliklinik
Mainz, Germany, 55131
University of Munster
Muenster, Germany, 48149
Israel
HaEmek MC
Afula, Israel, 18341
Rambam Medical Centre; Dept. of Dermatology
Haifa, Israel, 31096
Rabin Medical Centre; Dept. of Dermatology
Petach Tikva, Israel, 49100
Sheba Medical Center
Ramat Gan, Israel, 5262100
Sourasky Medical Centre
Tel-Aviv, Israel, 64239
Italy
Ambulatorio di Malattie Rare e Immunopatologia Cutanea
Florence, Lazio, Italy, 50125
Università di Parma Clinica Dermatologica
Parma, Lazio, Italy
U.O. Dermatologia Dipartimento Malattie Infettive Fondazione IRCCS Policlinico San Matteo
Pavia, Lazio, Italy, 27100
Centro Clinico per le genodermatosi Dipartimento di Dermatologia dell'Immacolata - IRCCS
Rome, Lazio, Italy, 00167
S.C. Dermatologia 2 - Ambulatorio Malattie Rare
Turin, Lazio, Italy, 10126
ASST DEGLI SPEDALI CIVILI DI BRESCIA; Clinica Dermatologica
Brescia, Lombardia, Italy, 25123
Spain
Clinica Universitaria de Navarra
Pamplona, Navarra, Spain, 31008
Hospital Clínic. Barcelona
Barcelona, Spain, 08036
Hosp. G. U Gregorio Marañón
Madrid, Spain, 28007
Hospital de la Victoria
Malaga, Spain, 29010
Turkey
Gülhane Military Medical Academy in Ankara
Ankara, Turkey
Akdeniz University Medical Faculty
Antalya, Turkey, 07059
Gaziantep University Medical Faculty Sahinbey Hospital
Gaziantep, Turkey
Bezm-i Alem University Medical Faculty
Istanbul, Turkey, 34093
Istanbul Uni Istanbul Medical Faculty
Istanbul, Turkey, 34093
Haydarpasa Numune Training and Research Hospital
Istanbul, Turkey, 34668
Marmara Uni
Istanbul, Turkey
Celal Bayar University Medical Faculty Hafsa Sultan Hospital
Manisa, Turkey, 45040
Karadeniz Teknik Üniversitesi Tıp Fakültesi Farabi Hastanesi
Trabzon, Turkey
Ukraine
Dnipropetrovsk State Medical Academy
Dnipropterovsk, Ukraine
Territorial Medical Association "Dermatovenerologia"
Kyiv, Ukraine, 01032
Uzhgorod State National Uni ; Course of Dermatology
Uzhgorod, Ukraine, 88011
Sponsors and Collaborators
Hoffmann-La Roche
Genentech, Inc.
Investigators
Study Director: Clinical Trials Hoffmann-La Roche

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02383589     History of Changes
Other Study ID Numbers: WA29330
2014-000382-41 ( EudraCT Number )
First Posted: March 9, 2015    Key Record Dates
Last Update Posted: January 23, 2019
Last Verified: January 2019

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