Clinical and Immunological Long-term Follow-up of Patients With Pemphigus Included in the "RITUXIMAB 3" Trial (LTFURITUX3)

• ClinicalTrials.gov Identifier: NCT03790293
• Recruitment Status: Unknown
• First Posted: December 31, 2018
• Last Update Posted: December 31, 2018
• Sponsor: University Hospital, Rouen
• Information provided by (Responsible Party): University Hospital, Rouen

Study Description

Brief Summary:

Pemphigus is an autoimmune disease specific to the skin and mucous membranes characterized by the production of IgG4 isotype autoantibodies (AC) directed mainly against two proteins involved in interkeratinocyte adhesion: desmoglein 1 (Dsg1 ) and desmoglein 3 (Dsg3) (1-3). The binding of auto-AC on these proteins disrupts their adhesion function, resulting in inter-keratinocyte dysjunction called "acantholysis" responsible for the formation of intraepidermal bubbles.

Treatment of pemphigus is typically based on systemic corticosteroids. High doses are usually necessary because of the frequent cortico-resistance of the disease. In recent years, several studies have focused on the treatment of pemphigus with anti-CD20: rituximab. The "Ritux 3" study (NCT00784589), a randomized, multicentre, randomized, non-blind clinical trial involving 90 patients, found that the use of rituximab as first-line therapy in combination with short corticosteroid therapy was extremely effective and that cortisone sparing was thus obtained limited the occurrence of side effects of treatment. On the other hand, this study showed that the 2 rituximab maintenance infusions of 500 mg to M12 and M18 allowed the maintenance of a high rate of complete remission up to the 3rd year of follow-up.

Questions remain to explain the long-term action of rituximab, in particular that of the evolution of these auto-reactive B cells (specific DSG) away from lymphocyte reconstitution B, as well as the evolution of auto-AC. anti-DSG and total IgG CAs, so as to ensure that the disappearance of the auto-reactive compartment is not accompanied by a long-term overall immunosuppression (and therefore a possible risk of infection).

The immunological changes induced in the long term as well as the precise mechanism of action of these treatments and particularly rituximab which allows a complete remission 5 years after treatment in many patients remain little known.

Condition or disease	Intervention/treatment	Phase
Autoimmune Diseases	Drug: Rituximab; Drug: corticosteroids'therapy	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment

Intervention Model Description

Patients included and treated in the RITUXIMAB 3 study (NCT00784589):

• Rituximab in combination with reduced corticosteroids
• Standard corticosteroid

• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Clinical and Immunological Long-term Follow-up of Patients With Pemphigus Included in the "RITUXIMAB 3" Trial With Medico-economic Evaluation of the Treatment.
• Estimated Study Start Date: December 2019
• Estimated Primary Completion Date: December 2019
• Estimated Study Completion Date: December 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Rituximab; Rituximab in combination with reduced corticosteroids is administrated	Drug: Rituximab; Patient was enrolled into the RITUXIMAB 3 study in the arm Rituximab in association with low corticosteroids'therapy; Drug: corticosteroids'therapy; Patient was enrolled into the RITUXIMAB 3 study in the arm Patient was enrolled into the RITUXIMAB 3 study in the arm standard corticosteroid
Active Comparator: Standard corticosteroid; Standard corticosteroid is administrated	Drug: corticosteroids'therapy; Patient was enrolled into the RITUXIMAB 3 study in the arm Patient was enrolled into the RITUXIMAB 3 study in the arm standard corticosteroid

Outcome Measures

Primary Outcome Measures :

1. Evaluate the occurrence of long-term serious AEs and AEs in patients initially randomized in the rituximab arm and in those who have secondarily received the product during the course of their pemphigus [ Time Frame: 1 day: 5 to 7 years after the inclusion into RITUXIMAB 3 study ]
   Collect of SAE and AE
2. Evaluate the long-term relapse rate in patients initially randomized in the rituximab arm and in those who have secondarily received the product during the course of their pemphigus [ Time Frame: 1 day: 5 to 7 years after the inclusion into RITUXIMAB 3 study ]
   Collect of relapses

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patient included in the RITUXIMAB 3 study
• Major patient who has read and understood the newsletter and signed the consent form

Exclusion Criteria:

• Person deprived of liberty by an administrative or judicial decision
• Person placed under the safeguard of justice
• Person under tutorship or curators
• Pregnant or lactating woman

Contacts and Locations

Contacts

Contact: Pascal JOLY; 0033232886841; pascal.joly@chu-rouen.fr

Sponsors and Collaborators

University Hospital, Rouen

More Information

• Responsible Party: University Hospital, Rouen
• ClinicalTrials.gov Identifier: NCT03790293
• Other Study ID Numbers: 2018/070/HP
• First Posted: December 31, 2018
• Last Update Posted: December 31, 2018
• Last Verified: December 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Pemphigus; Autoimmune Diseases; Immune System Diseases; Skin Diseases, Vesiculobullous; Skin Diseases; Rituximab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents