Resumen

Este es un ensayo clínico de fase III, aleatorizado, doble ciego, doble simulación, con comparador activo, de brazos paralelos, multicéntrico, para evaluar la eficacia y seguridad de rituximab en comparación con MMF en participantes con pénfigo vulgar (PV) moderado a gravemente activo que requieren 60-120 miligramos por día (mg/día) de prednisona oral o equivalente. Los participantes deben tener un diagnóstico confirmado de PV dentro de los 24 meses previos (mediante biopsia de piel o mucosa e inmunohistoquímica) y evidencia de enfermedad activa en la evaluación de selección. Se inscribirán aproximadamente 135 participantes en hasta 60 centros a nivel mundial. Los participantes serán aleatorizados en una proporción 1:1 para recibir rituximab más placebo de MMF o placebo de rituximab más MMF. La aleatorización será estratificada por duración de la enfermedad. El estudio constará de tres períodos: un período de selección de hasta 28 días, un período de tratamiento doble ciego de 52 semanas y un período de seguimiento de seguridad de 48 semanas que comienza al momento de la finalización o discontinuación del tratamiento del estudio.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 75 YearsSexo: ALL

Criterios de inclusión

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

Criterios de exclusión

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

Intervenciones

drug

Mycophenolate Mofetil Placebo

MMF matching placebo will be administered orally Q12H.

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.

drug

Rituximab

Rituximab will be administered at a dose of 1000 mg via IV infusion.

drug

Rituximab Placebo

Rituximab matching placebo will be administered via IV infusion.

Estudio aleatorizado, doble ciego, doble simulación, con comparador activo, multicéntrico, para evaluar la eficacia y seguridad de rituximab versus MMF en pacientes con pénfigo vulgar

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Mycophenolate Mofetil Placebo

Mycophenolate Mofetil

Rituximab

Rituximab Placebo

Ubicaciones

Hospital Italiano

Hospital Luis Lagomaggiore

Hospital Austral

Centro de Investigaciones Médicas - CIM

Patrocinadores