Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00007947

Trial Description

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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

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

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.

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Brief Summary in Scientific Language

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Organizational Data

  •   DRKS00007947
  •   2015/03/31
  •   2015/03/04
  •   no
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Secondary IDs

  •   2014-000382-41 
  •   NCT02383589  (ClinicalTrials.gov)
  •   WA29330  (Hoffmann-La Roche)
  •   2014-000382-41 
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Health Condition or Problem studied

  •   Pemphigus Vulgaris (PV)
  •   L10.0 -  Pemphigus vulgaris
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Interventions/Observational Groups

  •   Other: MMF placebo
  •   Drug: mycophenolate mofetil
  •   Drug: rituximab [MabThera/Rituxan]
  •   Other: rituximab placebo
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Blinded
  •   patient/subject, investigator/therapist
  •   Active control
  •   Treatment
  •   Parallel
  •   III
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Primary Outcome

- 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

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Secondary Outcome

- 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

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Countries of Recruitment

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Locations of Recruitment

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Recruitment

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  •   2015/05/31
  •   124
  •   Multicenter trial
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   75   Years
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Additional 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

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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

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Addresses

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    • Hoffmann-La Roche
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    • Genentech, Inc.
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    • Hoffmann-La Roche
    • Clinical Trials 
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    • Reference Study ID Number: WA29330 www.roche.com/about_roche/roche_worldwide.htm 
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Sources of Monetary or Material Support

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    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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Status

  •   Recruiting planned
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Trial Publications, Results and other Documents

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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   3
  •   2015/03/25
* This entry means the parameter is not applicable or has not been set.