A Study of Mycophenolate Mofetil (CellCept) in Management of Patients With Lupus Nephritis.
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.
1 other identifier
interventional
370
17 countries
108
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jul 2005
Longer than P75 for phase_3
108 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 1, 2005
CompletedFirst Submitted
Initial submission to the registry
September 15, 2006
CompletedFirst Posted
Study publicly available on registry
September 18, 2006
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2007
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2010
CompletedResults Posted
Study results publicly available
December 6, 2011
CompletedDecember 6, 2011
October 1, 2011
1.7 years
September 15, 2006
August 11, 2011
October 31, 2011
Conditions
Outcome Measures
Primary Outcomes (2)
Induction Phase: Number of Patients Showing Treatment Response
Treatment response was adjudicated by a blinded clinical endpoints committee (CEC) and defined as: a) Decrease in proteinuria, defined as a decrease in the urine protein to creatinine ratio (UPCr) to \<3 in subjects with baseline proteinuria ≥3 UPCr or a decrease in the UPCr by ≥50% in subjects with proteinuria \<3 UPCr at Baseline, and b) Stabilization of serum creatinine or improvement. UPCr were derived from the 24 hour urine collection. Patients who did not show a treatment response at Week 24 or who withdrew earlier than Week 24 were considered non-responders.
24 weeks
Maintenance Phase: Kaplan-Meier Estimates of Percentage of Participants Treatment Failure Free, by Time Interval
Treatment Failure was adjudicated by a clinical endpoints committee and was defined as the time to the earliest occurrence of any one of the following: death, end stage renal disease, sustained doubling of serum creatinine, renal flare, or a requirement for rescue therapy for exacerbation or deterioration of Lupus nephritis. Kaplan-Meier survival curves were estimated from the observed time to treatment failure for each patient. The data presented are the percentage of participants who were treatment-failure free at each time interval as estimated by Kaplan-Meier.
From the start of the Maintenance Phase to Month 36
Secondary Outcomes (12)
Induction Phase: Number of Participants Achieving Complete Remission
24 weeks
Induction Phase: Change From Baseline to Week 24 in Serum Creatinine
Baseline, Week 24
Induction Phase: Change From Baseline to Week 24 in 24-hour Urine Protein
Baseline, Week 24
Induction Phase: Change From Baseline to Week 24 in Serum Albumin
Baseline, Week 24
Induction Phase: Change in Renal British Isles Lupus Assessment Group (BILAG) Score
Baseline, 24 weeks
- +7 more secondary outcomes
Study Arms (4)
Induction Phase: Mycophenolate mofetil
EXPERIMENTALParticipants received oral mycophenolate mofetil (MMF) 1.5 g twice a day and concomitant corticosteroids for the 24 weeks of the Induction Phase.
Induction Phase: Cyclophosphamide
ACTIVE COMPARATORParticipants received monthly infusions of cyclophosphamide, 0.5 to 1.0 g per square meter of body surface area and concomitant treatment with corticosteroids for the 24 week Induction Phase.
Maintenance Phase: Mycophenolate mofetil
EXPERIMENTALParticipants received mycophenolate mofetil (MMF) 1.0 g orally twice a day, placebo to azathioprine orally once a day and corticosteroid for the 36 weeks Maintenance Phase.
Maintenance Phase: Azathioprine
ACTIVE COMPARATORParticipants received azathioprine (AZA) 2 mg/kg/day orally once a day, placebo to mycophenolate mofetil orally twice a day and corticosteroid for the 36 weeks Maintenance Phase.
Interventions
Supplied as 500 mg tablets taken orally twice a day (BID). Dose specific for each arm. Dosing started at 500 mg BID for the first week, increasing by 500 mg in subsequent weeks until the final target dose was reached.
Intravenous cyclophosphamide (IVC) was administered every four weeks (monthly) to a total of six infusions. Dosing was started at 0.75 g/m\^2 of body surface area for the first month, with subsequent doses at 0.5-1.0 g/m\^2. The target dose was 1.0 g/m\^2, but doses were titrated by 0.25 g/m\^2 increments to maintain nadir leukocyte count between 2500-4000/mm\^3.
2 mg/kg/day orally, provided as 50 mg capsules to be taken after meals.
Placebo capsules matching Azathioprine taken orally once a day.
Placebo tablets matching Mycophenolate mofetil taken orally twice daily.
Oral prednisolone (or equivalent) starting at a dose of 0.75-1.0 mg/kg/day (maximum 60 mg/day) tapered to 10 mg/day.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Hoffmann-La Rochelead
- Aspreva Pharmaceuticalscollaborator
Study Sites (108)
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Huntsville, Alabama, 35801, United States
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La Jolla, California, 92037, United States
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Los Angeles, California, 90095, United States
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San Francisco, California, 94143, United States
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San Leandro, California, 94578, United States
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Torrance, California, 90502, United States
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Miami, Florida, 33136, United States
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Atlanta, Georgia, 30303, United States
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Chicago, Illinois, 60611, United States
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Chicago, Illinois, 60637, United States
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Baltimore, Maryland, 21205, United States
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Boston, Massachusetts, 02115, United States
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Ann Arbor, Michigan, 48109-0358, United States
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Columbia, Missouri, 65212, United States
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Brooklyn, New York, 11203, United States
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Lake Success, New York, 11042, United States
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New York, New York, 10003, United States
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New York, New York, 10021, United States
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New York, New York, 10032, United States
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Chapel Hill, North Carolina, 27599-7280, United States
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Durham, North Carolina, 27710, United States
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Cleveland, Ohio, 44136, United States
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Columbus, Ohio, 43210, United States
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Oklahoma City, Oklahoma, 73104, United States
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Philadelphia, Pennsylvania, 19104, United States
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Pittsburgh, Pennsylvania, 15213, United States
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Charleston, South Carolina, 29425, United States
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Dallas, Texas, 75390, United States
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Buenos Aires, C1015ABO, Argentina
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Buenos Aires, C1425DQK, Argentina
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Córdoba, 5016, Argentina
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San Isidro, B1602BPPD, Argentina
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San Miguel de Tucumán, T4000AXL, Argentina
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Adelaide, SA 5000, Australia
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Camperdown, 2050, Australia
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Melbourne, 3168, Australia
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Parkville, 3052, Australia
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Woodville, 5011, Australia
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Brussels, 1200, Belgium
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Leuven, 3000, Belgium
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Liège, 4000, Belgium
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Rio de Janeiro, 20551-030, Brazil
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São Paulo, 04039-020, Brazil
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Sorocaba, 18030-210, Brazil
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Vancouver, British Columbia, V5Z 1L7, Canada
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Victoria, British Columbia, V8Z 7X8, Canada
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Halifax, Nova Scotia, B3H 2Y9, Canada
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London, Ontario, N6A 4V2, Canada
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Toronto, Ontario, M5T 2S8, Canada
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Montreal, Quebec, H1T 2M4, Canada
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Beijing, 100034, China
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Guangdong, 510008, China
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Guangzhou, 510630, China
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Jiangsu, 210002, China
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Shanghai, 200001, China
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Brno, 656 91, Czechia
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Prague, 128 08, Czechia
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Lille, 59037, France
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Lyon, 69437, France
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Nantes, 44035, France
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Paris, 75679, France
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Paris, 75877, France
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Toulouse, 31059, France
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Aachen, 52074, Germany
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Bad Bramstedt, 24576, Germany
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Berlin, 10117, Germany
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Berlin, 14059, Germany
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Dresden, 01307, Germany
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Düsseldorf, 40225, Germany
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Erlangen, 91054, Germany
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Hanover, 30625, Germany
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Leipzig, 04103, Germany
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München, 80336, Germany
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München, 81675, Germany
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Münster, 48149, Germany
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Athens, 11521, Greece
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Athens, 11527, Greece
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Heraklion, 71500, Greece
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Debrecen, 4032, Hungary
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Pécs, 7632, Hungary
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Szeged, 2724, Hungary
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Brescia, 25125, Italy
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Milan, 20149, Italy
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Padua, 35128, Italy
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Pisa, 56100, Italy
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Udine, 33100, Italy
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Mexico City, 14000, Mexico
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Mérida, 97000, Mexico
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San Luis Potosí City, 78240, Mexico
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Lisbon, Portugal
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Porto, 4200-319, Portugal
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Alicante, 03010, Spain
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Barcelona, 08035, Spain
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Barcelona, 08036, Spain
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Madrid, 28041, Spain
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Málaga, 29010, Spain
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Santander, 39008, Spain
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Seville, 41013, Spain
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Birmingham, B15 2TT, United Kingdom
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Cambridge, CB2 2QQ, United Kingdom
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Leeds, LS1 3EX, United Kingdom
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London, SE1 7EH, United Kingdom
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London, W12 OHS, United Kingdom
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London, WIT 4NJ, United Kingdom
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Manchester, M13 9WL, United Kingdom
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Newcastle upon Tyne, NE7 7DN, United Kingdom
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Sheffield, S10 2JF, United Kingdom
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Southampton, SO16 6YD, United Kingdom
Related Publications (5)
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.
PMID: 22922564DERIVEDDooley 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.
PMID: 22087680DERIVEDDall'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.
PMID: 21080348DERIVEDGinzler 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.
PMID: 20039429DERIVEDIsenberg 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.
PMID: 19933596DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
For many of the Maintenance Phase Outcomes, the total number of events precluded a meaningful time to event statistical analysis, therefore, only events numbers are reported.
Results Point of Contact
- Title
- Medical Communications
- Organization
- Hoffman-LaRoche
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 15, 2006
First Posted
September 18, 2006
Study Start
July 1, 2005
Primary Completion
March 1, 2007
Study Completion
March 1, 2010
Last Updated
December 6, 2011
Results First Posted
December 6, 2011
Record last verified: 2011-10