PemphigusPhase 4RITUX4NCT05898308
Comparison of a Personalized Maintenance Therapy With the Standard Treatment in Pemphigus
A Phase 4 study testing RiTUXimab Injection in people with Pemphigus and Dermatologic Disease, run by University Hospital, Rouen at 34 sites in 2 countries.
Trial summary
Pemphigus diseases are life-threatening chronic autoimmune blistering diseases characterized by split formation within the epidermis and surface-close epithelia accompanied by acantholysis. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Pemphigus, Dermatologic Disease
- What is being tested?
- RiTUXimab Injection
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 133 participants
- Where
- 34 sitesin 2 countries
- Study dates
- 4 Dec 2024to 1 May 2032
- Phase
- Phase 4
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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 and ≤ 80 years
- Signed Informed Consent Form (or from the family in case of impossibility of patient's consent).
- Confirmed newly diagnosed PV or PF, based on the presence of the following: histological features of acantholysis on skin or mucosal biopsy, and deposition of IgG, complement component 3, or both on the keratinocyte membrane detected by direct immunofluorescence on affected skin or mucosa
- Presence of moderate-to-severely active disease, defined by an overall PDAI score> 1554
- Patient able to receive the standard-of-care consisting of corticosteroids (prednisone 1 mg/kg/day PO) and rituximab
- Patients must be vaccinated against Covid-19 before study entry. It is recommended that patients are vaccinated against influenza and Streptococcus pneumoniae and have their first injection (Prevenar 13) before study entry.
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- For women who are not postmenopausal (menopausal: ≥ 12 months of non-therapy-induced amenorrhoea) or surgically sterile (absence of ovaries and/or uterus + bilateral salphingectomy) and who do not plan on having children anymore: agreement to remain abstinent or use two adequate methods of contraception, including at least one method with a failure rate of <1% per year, during the treatment period and for at least 12 months after the last dose of study treatment. They must have a negative result from a blood beta-HCG test within 1 week prior to randomization 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.
- For men: Surgical sterility or 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.
- Able to comply with the study protocol, in the investigator's judgment
- Patient affiliated with, or beneficiary of a social security (national health insurance) plan
Who cannot join
- Non-consenting patient or patient who cannot be followed regularly.
- Diagnosis of paraneoplastic pemphigus or evidence of other non-PV or PF autoimmune blistering disease
- Contraindication to rituximab marketed as 500 mg concentrate for solution for infusion
- Contraindication to prednisone marketed as 20 mg, scored tablet pharmaceutical form
- Contraindication to methylprednisolone marketed as 120 mg powder for injectable solution pharmaceutical form
- Contraindication to paracetamol marketed as 10 mg/mL solution for infusion pharmaceutical form
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- Contraindication to dexchlorpheniramine maleate marketed as 5 mg/1mL injectable solution pharmaceutical form
- Lack of peripheral venous access
- Pregnant or lactating
- 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- excluding transitory treatments (such as a corticosteroid therapy prescribed for a few days for an acute infection), and chronic corticosteroid treatments with a prednisone / prednisolone dose ≤20 mg/day, (these latter patients remain eligible for study entry)
- Treatment with IV Ig, plasmapheresis, or other similar procedure within 8 weeks prior to randomization
- Patients having received immunosuppressive treatment (such as cyclosporine, mycophenolate mofetil, azathioprine given at an effective dose for any other condition than Pemphigus, or any other treatment that might potentially be active on Pemphigus lesions (anti-TNF) within 4 weeks prior to baseline
- Treatment with cyclophosphamide within 12 weeks prior to randomization
- Patients with positive blood test for HIV
- Inherited or acquired severe immune deficiency
- 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.
- Patients with a currently treated cancer, including solid tumors, hematologic malignancies, and carcinoma (except basal cell of the skin and squamous cell carcinoma of the skin which can be easily cured with a standard excision )
- Patients with a past history ( < 5 years) of cancer, including solid tumors, hematologic malignancies, and carcinoma (except complete excision of basal cell of the skin and squamous cell carcinoma of the skin that have been excised and cured) NB: Patients whose cancer is cured and do not have anti-cancer treatment anymore must be referred to an oncologist before entry in the study
- 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.
- Major biological abnormality which in the investigator's judgment, would preclude patient participation,
- Positive test results for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C virus (HCV) serology at screening
- Participation in another interventional clinical trial within 28 days prior to randomization and during the study
- Person deprived of liberty by administrative or judicial decision or placed under judicial protection (guardianship or supervision)
Trial locations and contacts
34 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
34 sites in 2 countries
France33 sites, 33 recruiting
- Recruiting
Chu Amiens
Amiens, 80054
Guillaume Chaby, 03 22 45 56 69, Chaby.Guillaume@chu-amiens.fr
Guillaume Chaby
- Recruiting
Chu Angers
Angers, 49100
Clémence Berthin, 02 41 35 34 19, Clemence.berthin@chu-angers.fr
Clémence Berthin
- Recruiting
Ch Argenteuil
Argenteuil, 51000
Emmanuel Mahe, 01 34 23 28 80, Emmanuel.mahe@ch-argenteuil.fr
Emmanuel Mahe
- Not yet recruiting
Ap-Hp Hopital Avicennes
Bobigny, 93000
Frédéric Caux, 01 48 95 51 89, frederic.caux@aphp.fr
Frédéric Caux
- Recruiting
Chu Bordeaux
Bordeaux, 33076
Anne Pham-Ledard, 05 57 65 64 32, anne.pham-ledard@chu-bordeaux.fr
Anne Pham-Ledard
- Recruiting
Chu Brest
Brest, 29200
Claire Abasq, 02.98.22.33.15, claire.abasq@chu-brest.fr
Claire Abasq
- Recruiting
CHU CAEN
Caen, 14033
Cécile Morice, 02 31 27 25 10, morice-c@chu-caen.fr
Cécile Morice
- Recruiting
Chu Clermont-Ferrand
Clermont-Ferrand, 63100
Michel D'Incan, 04 73 75 05 50, mdincan@chu-clermontferrand.Fr
Michel D'Incan
- Not yet recruiting
Ap-Hp Henri Mondor
Créteil, 94010
Saskia Oro, 01 49 81 25 01, saskia.oro@aphp.fr
Saskia Oro
- Recruiting
Chu Dijon
Dijon, 21000
Christophe Bedane, 05 55 05 64 30, christophe.bedane87@orange.fr
Christophe Bedane
- Recruiting
Ch Dunkerque
Dunkirk, 59385
Sophie Duvert-Lehembre, 03 28 28 51 74, Sophie.duvert-Lehembre@ch-dunkerque.fr
Sophie Duvert-Lehembre
- Recruiting
Gh Le Havre
Le Havre, 76290
Noémie Litrowski, 02 32 73 33 28, Noemie.litrowski@ch-havre.fr
Noémie Litrowski
- Recruiting
Ch Le Mans
Le Mans, 72037
Hervé Maillard, 02 43 43 43 58, hmaillard@ch-lemans.fr
Hervé Maillard
- Recruiting
Chu Lille
Lille, 59037
Sophie Duvert-Lehembre, 03 20 44 48 68, Sophie.duvert-Lehembre@ch-dunkerque.fr
Sophie Duvert-Lehembre
- Recruiting
Chu Limoges
Limoges, 87000
Salomé Fourmond, 07 60 36 14 66, Salome.FOURMOND@chu-limoges.fr
Salomé Fourmond
- Not yet recruiting
Hcl Edouard Herriot
Lyon, 69003
Denis Julien, 04 72 11 72 11, denis.jullien@chu-lyon.fr
Denis Julien
- Not yet recruiting
Ap-Hm La Timone
Marseille, 13385
Marie-Aleth Richard, 04 91 74 47 08, marie-aleth.richard@ap-hm.fr
Marie-Aleth Richard
- Not yet recruiting
Ap-Hm Hopital Nord
Marseille, 13915
Emmanuel Delaporte, 04 91 96 43 09, Emmanuel.delaporte@ap-hm.fr
Emmanuel Delaporte
- Recruiting
Chu Montpellier
Montpellier, 34295
Olivier Dereure, 04 67 33 69 06, o-dereure@chu-montpellier.fr
Olivier Dereure
- Recruiting
Chu Nantes
Nantes, 44000
Gaelle Querreux, 02 40 08 31 16, gaelle.quereux@chu-nantes.fr
Gaelle Querreux
- Recruiting
CH NIORT
Niort, 79000
Ingrid Kupfer, 05 49 78 23 91, Ingrid.kupfer@ch-niort.fr
Ingrid Kupfer
- Recruiting
Chr Orleans
Orléans, 45067
Raphaelle Binois, 02 38 74 48 53, Raphaelle.binois@chr-orleans.fr
Raphaelle Binois
- Not yet recruiting
Ap-Hp Saint Louis
Paris, 75010
Jean-David Bouaziz, 01 42 49 99 61, jean-david.bouaziz@aphp.fr
Jean-David Bouaziz
- Not yet recruiting
Ap-Hp Pitie Salpetriere
Paris, 75013
Stéphane Barete, 01 56 01 79 00
Stéphane Barete
- Not yet recruiting
Ap-Hp Hopital Cochin
Paris, 75014
Nicolas Dupin, 01 58 41 42 43, nicolas.dupin@cch.aphp.fr
Nicolas Dupin
- Not yet recruiting
Ap-Hp Bichat
Paris, 75018
Catherine Picard-Dahan, 01 40 25 82 40, catherine.picard-dahan@aphp.fr
Catherine Picard-Dahan
- Not yet recruiting
Hcl Lyon Sud
Pierre-Bénite, 69310
Sébastien Debarbieux, 04 78 86 33 33, sebastien.debarbieux@chu-lyon.fr
Sébastien Debarbieux
- Not yet recruiting
Chu Reims
Reims, 51092
Manuelle-Anne Viguier, 03 10 73 66 76
Manuelle-Anne Viguier
- Recruiting
Chu Rennes
Rennes, 35000
Clémence Saillard, 02 99 28 43 49, clemence.saillard@chu-rennes.fr
Clémence Saillard
- Recruiting
Chu Rouen
Rouen, 76031
Pascal Joly, 02 32 88 30 57, pascal.joly@chu-rouen.fr
Pascal Joly
- Recruiting
Chu Saint-Etienne
Saint-Etienne, 42270
Jean-Luc Perrot, 04 77 82 85 08, j.luc.perrot@chu-st-etienne.fr
Jean-Luc Perrot
- Recruiting
Chu Toulouse
Toulouse, 31059
Marion Marcaillou, 05.65.77.81.07, Marcaillou.m@chu-toulouse.fr
Marion Marcaillou
- Recruiting
Chu Tours
Tours, 37000
Emmanuelle Lebidre, 02 47 47 87 73, e.lebidre@chu-tours.fr
Emmanuelle Lebidre
Guadeloupe1 site, 1 recruiting
- Recruiting
Chu Guadeloupe
Pointe-à-Pitre, 97159
Nadège Cordel, 590 590 8914 86, nadege.cordel@chu-guadeloupe.fr
Nadège Cordel
About this study
Official title: Comparison of a Personalized Maintenance Therapy Based on the Evolution of Anti-desmoglein Antibodies as Biomarkers of Pemphigus Subclinical Activity, With the Standard Treatment (Rituximab + Corticosteroids) in Pemphigus
Pemphigus diseases are life-threatening chronic autoimmune blistering diseases characterized by split formation within the epidermis and surface-close epithelia accompanied by acantholysis. Autoantibodies (Abs) are mainly directed against two structural proteins of the epidermal/epithelial desmosome, desmoglein (Dsg) 1 and Dsg3. Two main pemphigus variants can be differentiated, pemphigus vulgaris (PV), and pemphigus foliaceus (PF). Diagnosis of PV and PF is based on the combination of the clinical picture, histological picture of acantholysis, direct immunofluorescence microscopy (DIF) of a perilesional biopsy and serology.
The present "Ritux 4" trial is the fourth academic study with the French study group on auto immune bullous skin diseases (Groupe Bulle) to assess the use of rituximab in auto immune bullous skin diseases, in particular pemphigus. The 3 previous trials have been published in outstanding Journals (N Engl J Med 2007, Science Transl Med 2013, The Lancet 2017 and 2020), and have led to the approval of rituximab in pemphigus by the FDA in 2018 and EMA in 2019. In addition, an industry-sponsored trial testing rituximab versus mycophenolate mofetil in pemphigus, that the investigators have largely contributed to design has been very recently accepted for publication in the N Engl J Med (2021).
The investigator hypothesize that a maintenance therapy using an infusion of 1g of rituximab at Month 6 in patients whose anti-Dsg Abs have not sufficiently decreased at Month 3 after the initial cycle of rituximab (persistence of anti-Dsg1 Abs> 20 UI/ml and/or anti-Dsg3 Abs> 130 UI/ml), and or had an initial PDAI score >45 ( first year of follow-up), and the re-treatment with 1g of rituximab of patients whose anti Dsg Abs re-increase during the evolution of pemphigus after the initial cycle of rituximab (anti-Dsg1 Abs> 20 IU/ml, anti-Dsg3 Abs> 50 UI/ml), could be effective in preventing the occurrence of relapses, thus avoiding to restart a CS treatment, and would provide benefit as compared with the current treatment strategy of retreating patients with 2 g of rituximab (1g at Day0 and Day14) combined with oral CS patients, once a clinical relapse occurs.
- Conditions
- Pemphigus, Dermatologic Disease
- Being tested
- RiTUXimab Injection
- Keywords
- Pemphigus, Rituximab, Biomarkers, Personalized medicine
- Medical subject headings
- Pemphigus, Skin Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RiTUXimab InjectionDrug
Patients assigned to the "personalized maintenance treatment" will be treated by additional RITUXIMAB injection depending on anti-Dsg Abs levels.
| Study group | Role | What they receive |
|---|---|---|
| "standard-of-care" arm | No intervention | Patients will be initially treated according to the French guidelines (PNDS) based on the Ritux-3 regimen: 1000 mg of rituximab on Day1-Day14, and 500 mg at Month 12 and Month 18, plus oral prednisone 1 mg/kg/day initially, with the aim to stop prednisone after 6 months. The prednisone dose could be increased up to 1.5 mg/kg/day in patients who do not achieve disease control with the initial 1 mg/kg/day dose. |
| "personalized maintenance treatment" arm | Experimental | Patients will be treated with the same regimen (1000 mg of rituximab on Day1-Day14, and 500 mg at Month 12 and Month 18, plus oral prednisone 1 mg/kg/day initially, with the aim to stop prednisone after 6 months), which will then be adapted according to the evolution of anti-Dsg Abs: During the initial phase of treatment: patients i) whose serum anti-Dsg Abs have not sufficiently decreased ii) and/or those who initially had a severe pemphigus (at the inclusion visit) defined by a PDAI score > 45) will receive 1 g of rituximab at Month 6 ; Beyond the second year from Month 22 (4 months after the Month 18 infusion of 500 mg of rituximab) until the end of the study: patients whose anti-Dsg3 Abs re-increase >50 UI/ml and/or anti-Dsg1Abs re-increase>20 UI/ml) will receive 1 g of rituximab. A maximum of 2 additional maintenance infusions of rituximab per year will be allowed during the study. Receives: Drug: RiTUXimab Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of relapses/ flares by patient-year, defined according to the pemphigus consensus statement
by the appearance of 3 or more new lesions a month that do not heal spontaneously within 1 week, or by the extension of established lesions, in a patient who has achieved disease control.
Unit : /patient/year
Measured: 7.5 years
Secondary outcomes (9)
Number of patients-years of additional rituximab infusions to avoid one relapse by year (Number needed to treat, NNT).
Unit: none (ratio of variables with the same dimension)
Measured: 7.5 years
Time to disease flare/ relapse
Unit : years
Measured: 7.5 years
Cumulative duration of complete remission during the study
Unit : % of the time
Measured: 7.5 years
Number of maintenance infusions of 2 g of rituximab per patient-year
Unit: /patient/year
Measured: 7.5 years
Cumulative dose of rituximab by patient-year
Unit : g/patient/year
Measured: 7.5 years
blood leukocytes (measured at D15, M1, then every 3 month from M3 to M48)
Unit : count/mL
Measured: 7.5 years
anti-Dsg1 IgG measured by ELISA (measured at D15, M1, M2, then every 3 month from M3 to M48)
Unit : UI/mL
Measured: 7.5 years
anti-Dsg3 IgG measured by ELISA (measured at D15, M1, M2, then every 3 month from M3 to M48
Unit : UI/mL
Measured: 7.5 years
Quality of life, using the French version of bullous specific QOL questionnaire
Measured at M1, M2, every 3 months from M3 to M48, averaged on all follow-up visits (area under curve) Unit : ABQOL/TABQOL points
Measured: 7.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2023
- Study start4 Dec 2024
- Primary completion1 May 2032 (estimated)
- Study completion1 May 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PemphigusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- In both arms, patients will be initially treated according to the French guidelines (PNDS) based on the Ritux-3 regimen: 1000 mg of rituximab on Day1-Day14, and 500 mg at Month 12 and Month 18, plus oral prednisone 1 mg/kg/day initially, with the aim to stop prednisone after 6 months. "standard-of-care" arm will be treated as mentioned above. "personalized maintenance treatment" arm will be treated with the same regimen, adapted according to the evolution of anti-Dsg Abs: During the initial phase of treatment: patients i) whose serum anti-Dsg Abs have not sufficiently decreased ii) and/or those who initially had a severe pemphigus (at the inclusion visit) defined by a PDAI score \> 45) will receive 1 g of rituximab at Month 6 ; the second year from Month 22 (4 months after the Month 18 infusion of 500 mg of rituximab) until the end of the study: patients whose anti-Dsg3 Abs re-increase \>50 UI/ml and/or anti-Dsg1Abs re-increase\>20 UI/ml) will receive 1 g of rituximab.
- Masking
- None (open label)
- Enrolment
- 133 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Rouen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pascal JOLY, Principal investigator, University Hospital, Rouen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05898308
- Sponsor's protocol ID
- 2020/0424/HP
- Acronym
- RITUX4
- Status last verified
- Feb 2026
- First submitted
- 26 May 2023
- Last updated
- 20 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No