A Randomized, Double-Blind Study to Evaluate the Efficacy and Safety of Rituximab Versus MMF in Patients With Pemphigus Vulgaris

Phase 1

• Conditions: Pemphigus Vulgaris (PV); MedDRA version: 17.1 Level: LLT Classification code 10052802 Term: Pemphigus vulgaris System Organ Class: 100000004858; Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

• Registration Number: EUCTR2014-000382-41-ES
• Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-12-22
• Last Update Posted: 16 December 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 135

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 ? 3% body surface involvement, including cutaneous and/or mucosal lesions
? Mucosal or cutaneous PDAI activity score of ? 3 and overall PDAI score of 15?45 (moderate-to-severely active disease)
? Receiving standard-of-care corticosteroids consisting of 60?120 mg/day PO prednisone or equivalent (1.0 ? 1.5 mg/kg/day) 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 < 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 < 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 93
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 31

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 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified