Comparison Between Rituximab Treatment and General Corticotherapy Treatment in Patients With Pemphigus (Rituximab 3)

• ClinicalTrials.gov Identifier: NCT00784589
• Recruitment Status: Completed
• First Posted: November 4, 2008
• Last Update Posted: June 14, 2017
• Sponsor: University Hospital, Rouen
• Information provided by (Responsible Party): University Hospital, Rouen

Tracking Information

• First Submitted Date: November 3, 2008
• First Posted Date: November 4, 2008
• Last Update Posted Date: June 14, 2017
• Study Start Date: July 2009
• Actual Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 3, 2008): Number of patients with pemphigus controlled 24 months after the start of Rituximab treatment [ Time Frame: 2 years ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: November 3, 2008): Number of patients with pemphigus with both cutaneous and mucosal lesions healing after 6 months of rituximab treatment [ Time Frame: 6 months ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Comparison Between Rituximab Treatment and General Corticotherapy Treatment in Patients With Pemphigus
• Official Title: Comparison Between Monoclonal Antibody CD20 Treatment (Rituximab (mabthéra))and General Corticotherapy Treatment in Patients With Pemphigus

Brief Summary

Pemphigus is a severe and sometimes life-threatening disease with a mortality rate between 5 and 10 percent depending on the severity of disease and age of patients.

The standard of care is high doses of corticosteroids (CS) (usually, prednisone, 1 to 1.5. mg/kg/day, which are often associated with immunosuppressive drugs i.e., azathioprine, mycophenolate mofetil, cyclophosphamide, cyclosporine, although only one randomised study has demonstrated the superiority of the combination of corticosteroids and immunosuppressive drugs as compared to corticosteroids alone (9). Because of the low frequency of the disease, control trials are difficult to conduct. Evaluation of the different treatment regimens proposed, i;e; corticosteroids alone, CS and immunosuppressive drugs, IV immunoglobulins or new therapeutic regimens such as rituximab (an anti-CD20 monoclonal antibody directed against B- lymphocytes) or immunoadsorbtion.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Pemphigus Disease

Intervention

• Drug: General Corticotherapy
  for patients with severe pemphigus : general corticotherapy Arm : 1.5mg/kg/d for 1 month, then 1.25mg/kg/d for 1 month, then 1mg/kg/d for 1 month, then 0.75 mg/kg/d for 1 month, then 0.5 mg/kg/d for 3 months, then 0.3 mg/kg/d for 3 months, then 0.2 mg/kg/d for 4 months, then 0.1 mg/kg/d for 4 months, for patients with moderated pemphigus : general corticotherapy Arm : 1mg/kg/d for 1 month, then 0.75mg/kg/d for 1 month, then 0.5mg/kg/d for 2 months, then 0.3 mg/kg/d for 2 months, then 0.2 mg/kg/d for 3 months, then 0.1 mg/kg/d for 3 months,
• Drug: Rituximab
  for patients with severe pemphigus : rituximab Arm : 1mg/kg/d for 1 month, then 0.75 mg/kg/d for 1 month, then 0.5 mg/kg/d for 1 month, then 0.3 mg/kg/d for 1 month, then 0.2 mg/kg/d for 1 month, then 0.1 mg/kg/d for 1 month for patients with moderated pemphigus : rituximab Arm : 0.5mg/kg/d for 1 month, then 0.30 mg/kg/d for 1 month, then 0.2 mg/kg/d for 1 month,

Study Arms

• Experimental: Rituximab
  Intervention: Drug: Rituximab
• Active Comparator: Corticotherapy
  General Corticotherapy
  Intervention: Drug: General Corticotherapy

Publications *

• Mignard C, Maho-Vaillant M, Golinski ML, Balaye P, Prost-Squarcioni C, Houivet E, Calbo SB, Labeille B, Picard-Dahan C, Konstantinou MP, Chaby G, Richard MA, Bouaziz JD, Duvert-Lehembre S, Delaporte E, Bernard P, Caux F, Alexandre M, Ingen-Housz-Oro S, Vabres P, Quereux G, Dupuy A, Debarbieux S, Avenel-Audran M, D'Incan M, Bedane C, Beneton N, Jullien D, Dupin N, Misery L, Machet L, Beylot-Barry M, Dereure O, Sassolas B, Benichou J, Joly P, Hebert V; French Study Group on Autoimmune Bullous Skin Diseases. Factors Associated With Short-term Relapse in Patients With Pemphigus Who Receive Rituximab as First-line Therapy: A Post Hoc Analysis of a Randomized Clinical Trial. JAMA Dermatol. 2020 May 1;156(5):545-552. doi: 10.1001/jamadermatol.2020.0290.
• Joly P, Maho-Vaillant M, Prost-Squarcioni C, Hebert V, Houivet E, Calbo S, Caillot F, Golinski ML, Labeille B, Picard-Dahan C, Paul C, Richard MA, Bouaziz JD, Duvert-Lehembre S, Bernard P, Caux F, Alexandre M, Ingen-Housz-Oro S, Vabres P, Delaporte E, Quereux G, Dupuy A, Debarbieux S, Avenel-Audran M, D'Incan M, Bedane C, Beneton N, Jullien D, Dupin N, Misery L, Machet L, Beylot-Barry M, Dereure O, Sassolas B, Vermeulin T, Benichou J, Musette P; French study group on autoimmune bullous skin diseases. First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial. Lancet. 2017 May 20;389(10083):2031-2040. doi: 10.1016/S0140-6736(17)30070-3. Epub 2017 Mar 22.

Recruitment Information

• Recruitment Status: Completed
• Estimated Enrollment (submitted: November 3, 2008): 90
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: December 2016
• Actual Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• age >=18 and <= 80years
• consent obtained from patient
• effective female contraceptive method for women in procreate age
• new case of pemphigus vulgaris (PV) or pemphigus foliaceus (PF)

Exclusion Criteria:

• pemphigus vulgaris (PV) or pemphigus foliaceus (PF) treated
• pregnant woman or nursing mother
• woman able to have a baby and without contraception during the clinical trial period
• age < 18 or > 80
• karnovsky < 50%
• serious antecedents of allergy or anaphylactic reaction with human monoclonal antibody
• patient with depletion lymphocytic treatment in the next month
• unstable angina or ischemic heart disease
• cardiac insufficiency
• cardiac rhythm trouble uncontrolled
• positive HIV serology
• positive hepatitis B and / or C serology
• no consent

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT00784589
• Other Study ID Numbers: 2008/068/HP
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: University Hospital, Rouen
• Original Responsible Party: PAIRE Christian/Managing DIrector, University Hospital of Rouen
• Current Study Sponsor: University Hospital, Rouen
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Pascal JOLY, Professor; Clinique Dermatologique - Hôpitaux de Rouen

• PRS Account: University Hospital, Rouen
• Verification Date: June 2017