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Pemphigus VulgarisPhase 3NCT02383589

A Study to Evaluate the Efficacy and Safety of Rituximab Versus Mycophenolate Mofetil (MMF) in Participants With Pemphigus Vulgaris (PV)

A Phase 3 study testing Mycophenolate Mofetil and Rituximab in people with Pemphigus Vulgaris, run by Hoffmann-La Roche at 68 sites in 12 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Pemphigus Vulgaris
What is being tested?
Mycophenolate Mofetil and Rituximab
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
135 participants
Where
68 sitesin 12 countries
Study dates
26 May 2015to 29 Oct 2019
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

68 sites in 12 countries.

68 sites in 12 countries

United States15 sites

  • University of Alabama Birmingham

    Birmingham, Alabama, 35294

  • Massachusetts General Hospital Dermatology

    Boston, Massachusetts, 02114

  • Uni of NY and Roswell Cancer

    Buffalo, New York, 14203

  • Northwestern University

    Chicago, Illinois, 60611

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • Icahn School of Medicine at Mount Sinai

    New York, New York, 10029

  • Penn University

    Philadelphia, Pennsylvania, 19104

  • Oregon Health Sciences Uni

    Portland, Oregon, 97239

  • UC Davis Department of Dermatology

    Sacramento, California, 95816

  • Univ of Calif-San Francisco

    San Francisco, California, 94115

  • St Louis University Hospital

    St Louis, Missouri, 63104

  • Los Angeles Biomedical Research Institute

    Torrance, California, 90502

  • University of Arizona Medical Research Office

    Tucson, Arizona, 85724

  • Wake Forest Baptist Hospital Center for Dermatology Research

    Winston-Salem, North Carolina, 27104

Other trials in United States

Turkey (Türkiye)9 sites

  • Gülhane Military Medical Academy in Ankara

    Ankara

  • Akdeniz University Medical Faculty

    Antalya, 07059

  • Gaziantep University Medical Faculty Sahinbey Hospital

    Gaziantep

  • Bezm-i Alem University Medical Faculty

    Istanbul, 34093

  • Istanbul Uni Istanbul Medical Faculty

    Istanbul, 34093

  • Haydarpasa Numune Training and Research Hospital

    Istanbul, 34668

  • Marmara Uni

    Istanbul

  • Celal Bayar University Medical Faculty Hafsa Sultan Hospital

    Manisa, 45040

  • Karadeniz Teknik Üniversitesi Tıp Fakültesi Farabi Hastanesi

    Trabzon

Other trials in Turkey (Türkiye)

France8 sites

  • Department of Dermatology Avicenne Hospital & University

    Bobigny, 93000

  • CHU Hopitaux de Bordeaux

    CHU Hopitaux de Bordeaux, 33000

  • Centre Hospitalier Régional Universitaire de Lille (CHRU) - Hôpital Claude Huriez

    Lille, 59037

  • Les Hospices Civils de Lyon Dermatologie inflammatoire et médecine interne

    Lyon / Pierre Bénite, 69495

  • CHU de Reims

    Reims, 51100

  • CHU de Rennes - Hopital de Pontchaillo

    Rennes, 35033

  • CHU de Rouen - Hôpital Charles Nicolle

    Rouen, 76031

  • CHU Saint Etienne - Hôpital Nord

    Saint-Etienne, 42055

Other trials in France

Germany7 sites

  • Klinik und Poliklinik für Dermatologie und Venerologie Universitätsklinikum Köln

    Cologne, 50937

  • University Hospital for Dermatology

    Dresden, 01304

  • Kompetenzzentrum Fragile Haut Klinik fur Dermatologie und Venerologie

    Freiburg im Breisgau, 79104

  • Universitätsklinikum Heidelberg

    Heidelberg, 69120

  • University Hospital Schleswig-Holstein

    Lübeck, 23538

  • Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR, Hautklinik und Poliklinik

    Mainz, 55131

  • University of Munster

    Münster, 48149

Other trials in Germany

Italy6 sites

  • ASST DEGLI SPEDALI CIVILI DI BRESCIA; Clinica Dermatologica

    Brescia, Lombardy, 25123

  • Ambulatorio di Malattie Rare e Immunopatologia Cutanea

    Florence, Lazio, 50125

  • Università di Parma Clinica Dermatologica

    Parma, Lazio

  • U.O. Dermatologia Dipartimento Malattie Infettive Fondazione IRCCS Policlinico San Matteo

    Pavia, Lazio, 27100

  • Centro Clinico per le genodermatosi Dipartimento di Dermatologia dell'Immacolata - IRCCS

    Rome, Lazio, 00167

  • S.C. Dermatologia 2 - Ambulatorio Malattie Rare

    Turin, Lazio, 10126

Other trials in Italy

Israel5 sites

  • HaEmek MC

    Afula, 18341

  • Rambam Medical Centre; Dept. of Dermatology

    Haifa, 31096

  • Rabin Medical Centre; Dept. of Dermatology

    Petah Tikva, 49100

  • Sheba Medical Center

    Ramat Gan, 5262100

  • Sourasky Medical Centre

    Tel Aviv, 6423906

Other trials in Israel

Argentina4 sites

  • Hospital Italiano

    Buenos Aires, C1181ACH

  • Hospital Luis Lagomaggiore

    Mendoza, 5500

  • Hospital Austral

    Pilar, Pcia de Buenos Aires, 1500

  • Centro de Investigaciones Médicas - CIM

    San Juan Bautista, 1888

Other trials in Argentina

Spain4 sites

  • Hospital Clínic. Barcelona

    Barcelona, 08036

  • Hosp. G. U Gregorio Marañón

    Madrid, 28007

  • Hospital de la Victoria

    Málaga, 29010

  • Clinica Universitaria de Navarra

    Pamplona, Navarre, 31008

Other trials in Spain

Brazil3 sites

  • Faculdade de Medicina de Botucatu - Hospital das Clínicas

    Botucatu, São Paulo, 18618-970

  • Santa Casa de São Paulo Hospital Central X

    São Paulo, São Paulo, 01221-020

  • Hospital das Clinicas - FMUSP

    São Paulo, São Paulo, 05403-000

Other trials in Brazil

Canada3 sites

  • University of Alberta

    Edmonton, Alberta, T6G 2G3

  • Lynde Institute for Dermatology

    Markham, Ontario, L3P 1X2

  • Guildford Dermatology

    Surrey, British Columbia, V3R 6A7

Other trials in Canada

Australia2 sites

  • St George Hospital

    Kogarah, New South Wales, New South Wales, 2217

  • Veracity Clinical Research

    Woolloongabba, Queensland, 4102

Other trials in Australia

Ukraine2 sites

  • Dnipropetrovsk State Medical Academy

    Dnipropterovsk

  • Territorial Medical Association "Dermatovenerologia"

    Kyiv, 01032

Other trials in Ukraine

About this study

Official 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

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.

Being tested
Mycophenolate Mofetil Placebo, Mycophenolate Mofetil, Rituximab, Rituximab Placebo
Medical subject headings
Pemphigus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Mycophenolate Mofetil PlaceboDrug

    MMF matching placebo will be administered orally Q12H.

  • Mycophenolate MofetilDrug

    Also called MMF, CellCept

    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.

  • RituximabDrug

    Also called MabThera/Rituxan

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

  • Rituximab PlaceboDrug

    Also called MabThera/Rituxan

    Rituximab matching placebo will be administered via IV infusion.

Study groups in NCT02383589
Study groupRoleWhat they receive
Mycophenolate Mofetil (MMF)Active comparatorParticipants 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.
Receives: Drug: Mycophenolate Mofetil; Drug: Rituximab Placebo
Rituximab (RTX)ExperimentalParticipants 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.
Receives: Drug: Mycophenolate Mofetil Placebo; Drug: Rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants (Excluding Telemedicine [TM] Participants) Who Achieved Sustained Complete Remission, Evaluated by the Pemphigus Disease Area Index (PDAI) Activity Score

    Measured: From Baseline up to 52 Weeks (up to clinical cut-off date (CCOD) of 28 November 2018)

Secondary outcomes (8)

  1. Cumulative Oral Corticosteroid Dose

    Measured: From Baseline up to 52 Weeks (up to CCOD of 28 November 2018)

  2. 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.

    Measured: From Baseline up to 52 Weeks (up to CCOD of 28 November 2018)

  3. Time to Initial Sustained Complete Remission

    Measured: From Baseline up to 52 Weeks (up to CCOD of 28 November 2018)

  4. 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.

    Measured: From Baseline up to 52 Weeks (up to CCOD of 28 November 2018)

  5. 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.

    Measured: From Baseline up to 52 Weeks (up to CCOD of 28 November 2018)

  6. 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.

    Measured: Baseline up to 52 Weeks (up to CCOD of 28 November 2018)

  7. 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.

    Measured: Baseline up to 52 Weeks (up to CCOD of 28 November 2018)

  8. Percentage of Participants With Immunoglobulin (Ig) Levels Below Lower Limit of Normal (LLN)

    Measured: Baseline; Weeks 16, 24, 40 and 52; (end of treatment: up to Week 52) (up to CCOD of 28 November 2018)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Mar 2015 (estimated)
  2. Study start26 May 2015
  3. Primary completion28 Nov 2018
  4. Study completion29 Oct 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
135 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02383589
Sponsor's protocol ID
WA29330
Other IDs
2014-000382-41, 2014
Status last verified
Oct 2020
First submitted
4 Mar 2015
Last updated
10 Nov 2020

Publications

  • Werth VP, Joly P, Mimouni D, Maverakis E, Caux F, Lehane P, Gearhart L, Kapre A, Pordeli P, Chen DM; PEMPHIX Study Group. Rituximab versus Mycophenolate Mofetil in Patients with Pemphigus Vulgaris. N Engl J Med. 2021 Jun 17;384(24):2295-2305. doi: 10.1056/NEJMoa2028564. Epub 2021 May 19.

    PubMed 34097368

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Mycophenolate Mofetil and Rituximab in people with Pemphigus Vulgaris, run by Hoffmann-La Roche at 68 sites in 12 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 68 sites in United States, Turkey (Türkiye), France, Germany, Italy and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants (Excluding Telemedicine [TM] Participants) Who Achieved Sustained Complete Remission, Evaluated by the Pemphigus Disease Area Index (PDAI) Activity Score (time frame: From Baseline up to 52 Weeks (up to clinical cut-off date (CCOD) of 28 November 2018)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02383589, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Nov 2020.

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