Enteric-coated Mycophenolate Sodium Versus Azathioprine for the Extra-renal Lupus Manifestations

NCT01112215 | Completed Phase 4 DMC

• 1 other identifier: 2008-008934-35
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

Brief Summary

Azathioprine is still considered the treatment of choice for the non-renal manifestations of systemic lupus erythematosus (SLE) with an estimated efficacy of 45%.Recently, several studies have demonstrated the efficacy of mycophenolate mofetil/enteric-coated mycophenolate sodium in those cases, but so far, no controlled, randomized comparative study between the two drugs has been conducted. The aim is to perform a randomized, controlled, phase III/IV study comparing enteric-coated mycophenolate (ECMs) with azathioprine for induction and maintenance therapy of the non-renal manifestations of SLE. Methods: Patients with non-renal SLE flares (SLEDAI≥6 and/or BILAG o 2B refractory to full doses of hydroxychloroquine and prednisolone (≥10 mg/d) or with relapsing flares will be included. Patients will be stratified according the flare severity (moderate (SLEDAI\<12)-severe (SLEDAI≥12)) and randomized (1:1) into two groups of treatment, EMCs (2gr/d) or AZA (2-2.5mg/kg/d) according to TMPT levels for 6 months. Dose will be progressively tapered based on clinical response up to completing a year of treatment. The main aim is the percentage of complete remission achieved ((SLEDAI \<4 and/or absence of any BILAG A o B) at week 12 and 24 for moderate and severe flares, respectively. Secondary objectives include evaluating the reduction in the steroid requirement, number of flares post-treatment, effect on the biological parameters, and impact on quality of life, damage and drug safety. To detect a 20% difference between the two drugs with a 80% statistical power (0.05 alpha error), considering a follow up loss of 20%, a total of 240 patients is required.

Conditions

Systemic Lupus Erythematosus

Keywords

SLE; non-renal manifestations

Outcome Measures

Primary Outcomes (1)

• Obtention of complete remission

  Complete remission will be defined by a SLEDAI\<4 and/or absence of any BILAG A or B after 12 weeks of treatment

  24 months

Secondary Outcomes (1)

• To evaluate the safety, improvement in biological parameters and reduction of number of extra-renal flares.

  24 months

Study Arms (2)

azathioprine

ACTIVE COMPARATOR

Drug: Azathioprine

Enteric-coated Mycophenolate Sodium

ACTIVE COMPARATOR

Drug: Enteric-Coated Mycophenolate Sodium

Interventions

Azathioprine DRUG

Initial dose of 2-2.5 mg/kg (according to TMTP levels) for 6 months according the severity of the flare with progressive tapering if complete remission has been obtained

azathioprine

Enteric-Coated Mycophenolate Sodium DRUG

Initial dose of 1440 mg/day for 6 months to be tapered progressively if complete remission had been obtained

Enteric-coated Mycophenolate Sodium

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age\>18 years
• Fulfill at least 4 of the 11 criteria for the ACR classification
• Any extra-renal flare with an SLEDAI\>6 and/or one BILAG A or 2 B

You may not qualify if:

• Presence of active renal disease
• Previous intolerance or hypersensibility to any of the active components
• Active infection
• Unmeasurable levels of TMPT
• Pregnancy
• Presence of a severe flare that requires other immunosuppressive treatment for its control
• Any Psychiatric or social condition that did not ensure the patient´s follow-up and patient´s collaboration
• Previous treatment with EC-MPS or Azathioprine in the last 2 months
• Previous treatment with biological therapy in the last 3 months for anti-TNF therapy or in the last year for anti-CD20 therapy
• ALT or GPT \>120 UI/mL non-lupus related in the last 30 days
• Leucopenia \<1000x10E6 non-lupus related in the last 30 days
• Symptoms related to other medical conditions non-lupus related such as antiphospholipid syndrome.

Sponsors & Collaborators

• Hospital Universitari Vall d'Hebron Research Institute: lead

Study Sites (1)

Vall d'Hebron Hospital

Barcelona, Barcelona, 08035, Spain

Location

Related Publications (2)

• Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.

  PMID: 33687069 DERIVED

• Ordi-Ros J, Saez-Comet L, Perez-Conesa M, Vidal X, Mitjavila F, Castro Salomo A, Cuquet Pedragosa J, Ortiz-Santamaria V, Mauri Plana M, Cortes-Hernandez J. Enteric-coated mycophenolate sodium versus azathioprine in patients with active systemic lupus erythematosus: a randomised clinical trial. Ann Rheum Dis. 2017 Sep;76(9):1575-1582. doi: 10.1136/annrheumdis-2016-210882. Epub 2017 Apr 27.

  PMID: 28450313 DERIVED

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

Azathioprine

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thionucleosides; Sulfur Compounds; Organic Chemicals; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• JOSEP ORDI-ROS, MD

  VALL D'HEBRON HOSPITAL

  STUDY DIRECTOR

• JOSEFINA CORTES HERNANDEZ, MD

  VALL D'HEBRON HOSPITAL

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2010
• First Posted: April 28, 2010
• Study Start: December 1, 2009
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: October 4, 2016

Record last verified: 2015-03

Locations

ES (1)