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Personalized maintenance therapy versus standard treatment for pemphigus

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

Phase 4 Interventional University Hospital, Rouen · NCT05898308

This trial tests whether using biomarkers to personalize rituximab maintenance therapy helps adults with moderate-to-severe pemphigus stay in remission longer than standard treatment.

Quick facts

PhasePhase 4
Study typeInterventional
Enrollment133 (estimated)
Ages18 Years to 80 Years
SexAll
SponsorUniversity Hospital, Rouen Academic / other
Drugs / interventionsrituximab, cyclophosphamide, prednisone
Locations34 sites (Amiens and 33 other locations)
Trial IDNCT05898308 on ClinicalTrials.gov

What this trial studies

Ritux 4 is a phase 4 interventional trial from the French Groupe Bulle comparing a biomarker-guided personalized maintenance regimen to the current standard-of-care (prednisone plus rituximab) for pemphigus. The trial enrolls adults with newly diagnosed pemphigus vulgaris or foliaceus confirmed by biopsy and direct immunofluorescence who have moderate-to-severe active disease. Participants receive rituximab injections as part of the maintenance strategy, with treatment decisions informed by antibody biomarkers in the personalized arm. This is the fourth academic trial from the group, building on earlier published rituximab studies in pemphigus.

Who should consider this trial

Good fit: Adults aged 18–80 with newly diagnosed moderate-to-severe pemphigus (PV or PF) confirmed by histology and DIF who can receive prednisone and rituximab and meet vaccination requirements are ideal candidates.

Not a fit: Patients with mild disease, those unable to receive rituximab or systemic corticosteroids, or those outside the specified age range are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could prolong remission periods, reduce relapses, and lower cumulative steroid exposure for patients.

How similar studies have performed: Previous trials from this group and others (published in high-impact journals) have shown that rituximab is effective in pemphigus, though biomarker-guided personalization is less extensively studied.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* 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.
* 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

Exclusion Criteria:

* 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
* 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)

Where this trial is running

Amiens and 33 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions PemphigusDermatologic DiseaseRituximabBiomarkersPersonalized medicine
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.