A Study to Evaluate the Efficacy and Safety of Rituximab Versus Mycophenolate Mofetil (MMF) in Participants With Pemphigus Vulgaris (PV)
Status: | Active, not recruiting |
---|---|
Conditions: | Skin and Soft Tissue Infections |
Therapuetic Areas: | Dermatology / Plastic Surgery |
Healthy: | No |
Age Range: | 18 - 75 |
Updated: | 1/25/2019 |
Start Date: | May 26, 2015 |
End Date: | November 7, 2019 |
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
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.
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.
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
We found this trial at
16
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University of Alabama at Birmingham The University of Alabama at Birmingham (UAB) traces its roots...
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Univ of Minnesota With a flagship campus in the heart of the Twin Cities, and...
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Icahn School of Medicine at Mount Sinai Icahn School of Medicine at Mount Sinai is...
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4618 Country Club Road
Winston-Salem, North Carolina 27104
Winston-Salem, North Carolina 27104
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