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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02383589




Registration number
NCT02383589
Ethics application status
Date submitted
4/03/2015
Date registered
9/03/2015
Date last updated
10/11/2020

Titles & IDs
Public title
A Study to Evaluate the Efficacy and Safety of Rituximab Versus Mycophenolate Mofetil (MMF) in Participants With Pemphigus Vulgaris (PV)
Scientific 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
Secondary ID [1] 0 0
2014-000382-41
Secondary ID [2] 0 0
WA29330
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pemphigus Vulgaris 0 0
Condition category
Condition code
Skin 0 0 0 0
Dermatological conditions
Skin 0 0 0 0
Other skin conditions
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Mycophenolate Mofetil Placebo
Treatment: Drugs - Mycophenolate Mofetil
Treatment: Drugs - Rituximab
Treatment: Drugs - Rituximab Placebo

Active Comparator: Mycophenolate Mofetil (MMF) - 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.

Experimental: Rituximab (RTX) - 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 twice daily Q12H from Day 1 to Week 52.


Treatment: Drugs: Mycophenolate Mofetil Placebo
MMF matching placebo will be administered orally Q12H.

Treatment: Drugs: 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.

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

Treatment: Drugs: Rituximab Placebo
Rituximab matching placebo will be administered via IV infusion.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants (Excluding Telemedicine [TM] Participants) Who Achieved Sustained Complete Remission, Evaluated by the Pemphigus Disease Area Index (PDAI) Activity Score
Timepoint [1] 0 0
From Baseline up to 52 Weeks (up to clinical cut-off date (CCOD) of 28 November 2018)
Secondary outcome [1] 0 0
Cumulative Oral Corticosteroid Dose
Timepoint [1] 0 0
From Baseline up to 52 Weeks (up to CCOD of 28 November 2018)
Secondary outcome [2] 0 0
Total Number of Protocol Defined Disease Flares - Disease flare is defined as appearance of three or more new lesions a month that do not heal spontaneously within 1 week, or by the extension of established lesions, in a participant who has achieved disease control.
Timepoint [2] 0 0
From Baseline up to 52 Weeks (up to CCOD of 28 November 2018)
Secondary outcome [3] 0 0
Time to Initial Sustained Complete Remission
Timepoint [3] 0 0
From Baseline up to 52 Weeks (up to CCOD of 28 November 2018)
Secondary outcome [4] 0 0
Time to Protocol Defined Disease Flare - Disease flare is defined as the appearance of three or more new lesions a month that do not heal spontaneously within 1 week or by the extension of established lesions in a participant who has achieved disease control.
Timepoint [4] 0 0
From Baseline up to 52 Weeks (up to CCOD of 28 November 2018)
Secondary outcome [5] 0 0
Change in Health-Related Quality of Life (HRQoL), as Measured by the Dermatology Life Quality Index (DLQI) Score - Total DLQI scores range from 0 to 30 with higher DLQI scores reflecting greater impairment in a participant's health-related quality of life. The DLQI score is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. The measure type mean is the estimated mean from adjusted MMRM.
Timepoint [5] 0 0
From Baseline up to 52 Weeks (up to CCOD of 28 November 2018)
Secondary outcome [6] 0 0
Percentage of Participants With Adverse Events, Serious Adverse Events, and Corticosteroid-Related Adverse Events - An adverse event is any untoward medical occurrence in a participant to whom a medicinal product is administered and which does not necessarily have a causal relationship with this treatment. A serious adverse event is an adverse event that results in death or is life-threatening or requires/prolongs hospitalization or results in persistent/significant disability/incapacity or congenital abnormality/birth defect. Adverse events of Grade 3 of higher are severe and life-threatening adverse events CS-related adverse events - causality as determined by the investigator.
Timepoint [6] 0 0
Baseline up to 52 Weeks (up to CCOD of 28 November 2018)
Secondary outcome [7] 0 0
Percentage of Participants With Anti-Drug Antibodies (ADA) - Participants with treatment-induced and treatment-enhanced anti-drug antibodies. The clinical relevance of anti-rituximab antibody formation in RITUXAN treated pemphigus vulgaris (PV) participants is unclear.
Timepoint [7] 0 0
Baseline up to 52 Weeks (up to CCOD of 28 November 2018)
Secondary outcome [8] 0 0
Percentage of Participants With Immunoglobulin (Ig) Levels Below Lower Limit of Normal (LLN)
Timepoint [8] 0 0
Baseline; Weeks 16, 24, 40 and 52; (end of treatment: up to Week 52) (up to CCOD of 28 November 2018)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 0 0
St George Hospital - Kogarah, New South Wales
Recruitment hospital [2] 0 0
Veracity Clinical Research - Woolloongabba
Recruitment postcode(s) [1] 0 0
2217 - Kogarah, New South Wales
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Oregon
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
Argentina
State/province [13] 0 0
Buenos Aires
Country [14] 0 0
Argentina
State/province [14] 0 0
Florencio Varela
Country [15] 0 0
Argentina
State/province [15] 0 0
Mendoza
Country [16] 0 0
Argentina
State/province [16] 0 0
Pilar, Pcia De Buenos Aires
Country [17] 0 0
Brazil
State/province [17] 0 0
SP
Country [18] 0 0
Canada
State/province [18] 0 0
Alberta
Country [19] 0 0
Canada
State/province [19] 0 0
British Columbia
Country [20] 0 0
Canada
State/province [20] 0 0
Ontario
Country [21] 0 0
France
State/province [21] 0 0
Bobigny
Country [22] 0 0
France
State/province [22] 0 0
CHU Hopitaux De Bordeaux
Country [23] 0 0
France
State/province [23] 0 0
Lille
Country [24] 0 0
France
State/province [24] 0 0
Lyon / Pierre Bénite
Country [25] 0 0
France
State/province [25] 0 0
Reims
Country [26] 0 0
France
State/province [26] 0 0
Rennes
Country [27] 0 0
France
State/province [27] 0 0
Rouen
Country [28] 0 0
France
State/province [28] 0 0
Saint Etienne
Country [29] 0 0
Germany
State/province [29] 0 0
Dresden
Country [30] 0 0
Germany
State/province [30] 0 0
Freiburg
Country [31] 0 0
Germany
State/province [31] 0 0
Heidelberg
Country [32] 0 0
Germany
State/province [32] 0 0
Koeln
Country [33] 0 0
Germany
State/province [33] 0 0
Lübeck
Country [34] 0 0
Germany
State/province [34] 0 0
Mainz
Country [35] 0 0
Germany
State/province [35] 0 0
Muenster
Country [36] 0 0
Israel
State/province [36] 0 0
Afula
Country [37] 0 0
Israel
State/province [37] 0 0
Haifa
Country [38] 0 0
Israel
State/province [38] 0 0
Petach Tikva
Country [39] 0 0
Israel
State/province [39] 0 0
Ramat Gan
Country [40] 0 0
Israel
State/province [40] 0 0
Tel-Aviv
Country [41] 0 0
Italy
State/province [41] 0 0
Lazio
Country [42] 0 0
Italy
State/province [42] 0 0
Lombardia
Country [43] 0 0
Spain
State/province [43] 0 0
Navarra
Country [44] 0 0
Spain
State/province [44] 0 0
Barcelona
Country [45] 0 0
Spain
State/province [45] 0 0
Madrid
Country [46] 0 0
Spain
State/province [46] 0 0
Malaga
Country [47] 0 0
Turkey
State/province [47] 0 0
Ankara
Country [48] 0 0
Turkey
State/province [48] 0 0
Antalya
Country [49] 0 0
Turkey
State/province [49] 0 0
Gaziantep
Country [50] 0 0
Turkey
State/province [50] 0 0
Istanbul
Country [51] 0 0
Turkey
State/province [51] 0 0
Manisa
Country [52] 0 0
Turkey
State/province [52] 0 0
Trabzon
Country [53] 0 0
Ukraine
State/province [53] 0 0
Dnipropterovsk
Country [54] 0 0
Ukraine
State/province [54] 0 0
Kyiv

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Genentech, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02383589
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications