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 1

• Conditions: Pemphigus diseases (Pemphigus Vulgaris - PV and Pemphigus Foliaceus (PF).; MedDRA version: 20.1Level: PTClassification code 10067776Term: Ocular pemphigoidSystem Organ Class: 10015919 - Eye disorders; MedDRA version: 20.0Level: PTClassification code 10034277Term: PemphigoidSystem Organ Class: 10040785 - Skin and subcutaneous tissue disorders; MedDRA version: 21.1Level: LLTClassification code 10057052Term: Cicatricial pemphigoidSystem Organ Class: 10040785 - Skin and subcutaneous tissue disorders; Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

• Registration Number: EUCTR2022-000060-22-FR
• Lead Sponsor: CHU de Rouen

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-07-15
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 133

Inclusion Criteria

1) Age = 18 and = 80 years
2) Signed Informed Consent Form (or from the family in case of impossibility of patient’s consent).
3) 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
4) Presence of moderate-to-severely active disease, defined by an overall PDAI score> 1554
5) Patient able to receive the standard-of-care consisting of corticosteroids (prednisone 1 mg/kg/day PO) and rituximab
6) Patients must be vaccinated against Covid-19 before study entry. It is recommended that patients are vaccinated against influenza and pneumococcus and have their first injection (Prevenar 13) before study entry.
7) For women who are not postmenopausal (menopausal: = 12 months of non-therapy-induced amenorrhoea) or not sterile: 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.
8) 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.
9) Able to comply with the study protocol, in the investigator’s judgment
10) Patient affiliated with, or beneficiary of a social security (national health insurance) plan
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 33
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

Exclusion Criteria

1) Non-consenting patient or patient who cannot be followed regularly.
2) Diagnosis of paraneoplastic pemphigus or other non-PV or PF autoimmune blistering disease
3) Contraindication to rituximab marketed as 500 mg concentrate for solution for infusion
4) Contraindication to prednisone marketed as 20 mg scored tablet pharmaceutical form
5) Contraindication to methylprednisolone marketed as 120 mg powder for injectable solution pharmaceutical form
6) Contraindication to paracetamol marketed as 10 mg/mL solution for infusion pharmaceutical form
7) Contraindication to dexchlorpheniramine maleate marketed as 5 mg/1mL injectable solution pharmaceutical form
8) Lack of peripheral venous access
9) Pregnant or lactating women
10) Significant cardiovascular or pulmonary disease (including o bstructive pulmonary disease)
11) Uncontrolled concomitant disease that, in the investigator’s judgment, would preclude patient participation, including but not limited to nervous system, renal, hepatic, endocrine, or gastrointestinal disorders
12) 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)
13) Treatment with IV Ig, plasmapheresis, or other similar procedure (immunoadsorption) within 8 weeks prior to randomization
14) 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
15) Treatment with cyclophosphamide within 12 weeks prior to randomization
16) Patients with positive blood test for HIV
17) Inherited or acquired severe immune deficiency
18) Severe active infection (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. Entry into this study may be reconsidered once the infection has fully resolved.
19) 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 are small and localized and can be easily cured with a standard excision )
20) Patients with a past history ( < 5 years) of cancer, including solid tumors, hematologic malignancies, and carcinoma (except complete excision of basal cell carcinoma 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
21) Currently active alcohol or drug abuse, or history of alcohol or drug abuse within 24 weeks prior to screening
22) Major surgery within 4 weeks prior to randomization, excluding diagnostic surgery
23) Treatment with rituximab or a B cell-targeted therapy (e.g., anti-CD20, anti-CD22, or anti-BLyS) within 12 months prior to randomization
24) 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 entr

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified