Clinical trial NCT00377637: A Study of Mycophenolate Mofetil (CellCept) in Management of Patients With Lupus Nephritis.
Official title: A Prospective, Randomized, Active Controlled, Parallel Group, Multi-center Trial to Assess the Efficacy and Safety of Mycophenolate Mofetil (MMF) in Inducing Response and Maintaining Remission in Subjects With Lupus Nephritis.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lupus Nephritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
Collaborators: name: Aspreva Pharmaceuticals
First posted: 2006-09-18
Enrollment: 370
Sex: ALL
Minimum age (years): 12
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This 2 arm study assessed the efficacy of Mycophenolate Mofetil (MMF; CellCept) compared to cyclophosphamide in inducing a response in patients with lupus nephritis, and the long term efficacy of MMF compared to azathioprine in maintaining remission and renal function. Patients were randomized to receive either MMF (1.5 g twice daily \[bid\]) or cyclophosphamide (0.5-1.0 g/m\^2 in monthly pulses) in the induction phase. Those patients meeting criteria for response were re-randomized for entry into the maintenance phase, to receive either MMF (1 g bid) or azathioprine (2 mg/kg/day).


Eligibility criteria: Inclusion Criteria:

* male or female patients, 12-75 years of age;
* diagnosis of systemic lupus erythematosus;
* kidney biopsy within 6 months of study, with histological diagnosis of lupus nephritis;
* laboratory evidence of active nephritis.

Exclusion Criteria:

* continuous dialysis starting \>2 weeks before randomization into induction phase, and/or with an anticipated duration of \>8 weeks;
* previous or planned kidney transplant;
* other clinically significant active medical conditions.

Primary outcomes:
measure: Induction Phase: Number of Patients Showing Treatment Response
timeFrame: 24 weeks
measure: Maintenance Phase: Kaplan-Meier Estimates of Percentage of Participants Treatment Failure Free, by Time Interval
timeFrame: From the start of the Maintenance Phase to Month 36
Secondary outcomes:
measure: Induction Phase: Number of Participants Achieving Complete Remission
timeFrame: 24 weeks
measure: Induction Phase: Change From Baseline to Week 24 in Serum Creatinine
timeFrame: Baseline, Week 24
measure: Induction Phase: Change From Baseline to Week 24 in 24-hour Urine Protein
timeFrame: Baseline, Week 24
measure: Induction Phase: Change From Baseline to Week 24 in Serum Albumin
timeFrame: Baseline, Week 24
measure: Induction Phase: Change in Renal British Isles Lupus Assessment Group (BILAG) Score
timeFrame: Baseline, 24 weeks
measure: Induction Phase: Change From Baseline in Short-Form Health Survey (SF-36) Domain and Component Scores
timeFrame: Baseline and 24 weeks
measure: Maintenance Phase: Events Contributing to the Primary Endpoint: Number of Deaths
timeFrame: From the start of the Maintenance Phase to Month 36
measure: Maintenance Phase: Events Contributing to the Primary Endpoint: Number of Participants With End-stage Renal Disease (ESRD)
timeFrame: From the start of the Maintenance Phase to Month 36
measure: Maintenance Phase: Events Contributing to the Primary Endpoint: Number of Participants With Sustained Doubling of Serum Creatinine
timeFrame: From the start of the Maintenance Phase to Month 36
measure: Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Renal Flare Free, by Time Interval
timeFrame: From the start of the Maintenance Phase to Month 36
measure: Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Not Receiving Rescue Therapy
timeFrame: From the start of the Maintenance Phase to Month 36
measure: Maintenance Phase: Participants With Major Extra-renal Flare
timeFrame: From the start of the Maintenance Phase to Month 36
Other outcomes:
Locations:
city: Huntsville
country: United States
state: Alabama
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: San Francisco
country: United States
state: California
city: San Leandro
country: United States
state: California
city: Torrance
country: United States
state: California
city: Miami
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Chicago
country: United States
state: Illinois
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Ann Arbor
country: United States
state: Michigan
city: Columbia
country: United States
state: Missouri
city: Brooklyn
country: United States
state: New York
city: Lake Success
country: United States
state: New York
city: New York
country: United States
state: New York
city: New York
country: United States
state: New York
city: New York
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Durham
country: United States
state: North Carolina
city: Cleveland
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Dallas
country: United States
state: Texas
city: Buenos Aires
country: Argentina
city: Buenos Aires
country: Argentina
city: Córdoba
country: Argentina
city: San Isidro
country: Argentina
city: Tucuman
country: Argentina
city: Adelaide
country: Australia
city: Camperdown
country: Australia
city: Melbourne
country: Australia
city: Parkville
country: Australia
city: Woodville
country: Australia
city: Bruxelles
country: Belgium
city: Leuven
country: Belgium
city: Liege
country: Belgium
city: Rio de Janeiro
country: Brazil
city: Sao Paulo
country: Brazil
city: Sorocaba
country: Brazil
city: Vancouver
country: Canada
state: British Columbia
city: Victoria
country: Canada
state: British Columbia
city: Halifax
country: Canada
state: Nova Scotia
city: London
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Beijing
country: China
city: Guangdong
country: China
city: Guangzhou
country: China
city: Jiangsu
country: China
city: Shanghai
country: China
city: Brno
country: Czech Republic
city: Praha 2
country: Czech Republic
city: Lille
country: France
city: Lyon
country: France
city: Nantes
country: France
city: Paris
country: France
city: Paris
country: France
city: Toulouse
country: France
city: Aachen
country: Germany
city: Bad Bramstedt
country: Germany
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Dresden
country: Germany
city: Düsseldorf
country: Germany
city: Erlangen
country: Germany
city: Hannover
country: Germany
city: Leipzig
country: Germany
city: Muenster
country: Germany
city: München
country: Germany
city: München
country: Germany
city: Athens
country: Greece
city: Athens
country: Greece
city: Heraklion
country: Greece
city: Debrecen
country: Hungary
city: Pécs
country: Hungary
city: Szeged
country: Hungary
city: Brescia
country: Italy
city: Milano
country: Italy
city: Padova
country: Italy
city: Pisa
country: Italy
city: Udine
country: Italy
city: Merida
country: Mexico
city: Mexico City
country: Mexico
city: San Luis Potosi
country: Mexico
city: Lisboa
country: Portugal
city: Porto
country: Portugal
city: Alicante
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Malaga
country: Spain
city: Santander
country: Spain
city: Sevilla
country: Spain
city: Birmingham
country: United Kingdom
city: Cambridge
country: United Kingdom
city: Leeds
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Newcastle Upon Tyne
country: United Kingdom
city: Sheffield
country: United Kingdom
city: Southampton
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Sundel R, Solomons N, Lisk L; Aspreva Lupus Management Study (ALMS) Group. Efficacy of mycophenolate mofetil in adolescent patients with lupus nephritis: evidence from a two-phase, prospective randomized trial. Lupus. 2012 Nov;21(13):1433-43. doi: 10.1177/0961203312458466. Epub 2012 Aug 24.
citation: Dooley MA, Jayne D, Ginzler EM, Isenberg D, Olsen NJ, Wofsy D, Eitner F, Appel GB, Contreras G, Lisk L, Solomons N; ALMS Group. Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis. N Engl J Med. 2011 Nov 17;365(20):1886-95. doi: 10.1056/NEJMoa1014460.
citation: Dall'Era M, Stone D, Levesque V, Cisternas M, Wofsy D. Identification of biomarkers that predict response to treatment of lupus nephritis with mycophenolate mofetil or pulse cyclophosphamide. Arthritis Care Res (Hoboken). 2011 Mar;63(3):351-7. doi: 10.1002/acr.20397. Epub 2010 Nov 15.
citation: Ginzler EM, Wofsy D, Isenberg D, Gordon C, Lisk L, Dooley MA; ALMS Group. Nonrenal disease activity following mycophenolate mofetil or intravenous cyclophosphamide as induction treatment for lupus nephritis: findings in a multicenter, prospective, randomized, open-label, parallel-group clinical trial. Arthritis Rheum. 2010 Jan;62(1):211-21. doi: 10.1002/art.25052.
citation: Isenberg D, Appel GB, Contreras G, Dooley MA, Ginzler EM, Jayne D, Sanchez-Guerrero J, Wofsy D, Yu X, Solomons N. Influence of race/ethnicity on response to lupus nephritis treatment: the ALMS study. Rheumatology (Oxford). 2010 Jan;49(1):128-40. doi: 10.1093/rheumatology/kep346. Epub 2009 Nov 20.