Comparison of a Personalized Maintenance Therapy With the Standard Treatment in Pemphigus

Sponsor
University Hospital, Rouen
Study ID
NCT05898308
Phase
PHASE4
Status
Recruiting
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Conditions

  • Dermatologic Disease
  • Pemphigus

Eligibility Criteria

Sex
ALL
Age
18 Years - 80 Years
Healthy Volunteers
Not accepted

Interventions

  • RiTUXimab Injection — DRUG
    Patients assigned to the "personalized maintenance treatment" will be treated by additional RITUXIMAB injection depending on anti-Dsg Abs levels.

Study Details

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.

Key Dates

Start date
Dec 4, 2024
Status verified
Feb 2026
Primary completion
May 1, 2032
Completion
May 1, 2032

Study Design

Enrollment
133 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • No Intervention: "standard-of-care" arm
    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.
  • Experimental: "personalized maintenance treatment" arm
    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.

Primary Outcome Measure

Number of relapses/ flares by patient-year, defined according to the pemphigus consensus statement [ Time Frame: 7.5 years ]

Central Contacts

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