A Study of Mycophenolate Mofetil (CellCept) in Management of Patients With Lupus Nephritis.

NCT ID: NCT00377637

Last Updated: 2011-12-06

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

370 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-07-31

Study Completion Date

2010-03-31

Brief Summary

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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).

Detailed Description

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Conditions

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Lupus Nephritis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Induction Phase: Mycophenolate mofetil

Participants received oral mycophenolate mofetil (MMF) 1.5 g twice a day and concomitant corticosteroids for the 24 weeks of the Induction Phase.

Group Type EXPERIMENTAL

Mycophenolate mofetil (MMF)

Intervention Type DRUG

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.

Corticosteroid

Intervention Type DRUG

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.

Induction Phase: Cyclophosphamide

Participants 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.

Group Type ACTIVE_COMPARATOR

Cyclophosphamide

Intervention Type DRUG

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.

Corticosteroid

Intervention Type DRUG

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.

Maintenance Phase: Mycophenolate mofetil

Participants 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.

Group Type EXPERIMENTAL

Mycophenolate mofetil (MMF)

Intervention Type DRUG

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.

Placebo to Azathioprine

Intervention Type DRUG

Placebo capsules matching Azathioprine taken orally once a day.

Corticosteroid

Intervention Type DRUG

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.

Maintenance Phase: Azathioprine

Participants 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.

Group Type ACTIVE_COMPARATOR

Azathioprine

Intervention Type DRUG

2 mg/kg/day orally, provided as 50 mg capsules to be taken after meals.

Placebo to Mycophenolate mofetil

Intervention Type DRUG

Placebo tablets matching Mycophenolate mofetil taken orally twice daily.

Corticosteroid

Intervention Type DRUG

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.

Interventions

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Mycophenolate mofetil (MMF)

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.

Intervention Type DRUG

Cyclophosphamide

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.

Intervention Type DRUG

Azathioprine

2 mg/kg/day orally, provided as 50 mg capsules to be taken after meals.

Intervention Type DRUG

Placebo to Azathioprine

Placebo capsules matching Azathioprine taken orally once a day.

Intervention Type DRUG

Placebo to Mycophenolate mofetil

Placebo tablets matching Mycophenolate mofetil taken orally twice daily.

Intervention Type DRUG

Corticosteroid

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.

Intervention Type DRUG

Other Intervention Names

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CellCept Endoxan® Imuran®

Eligibility Criteria

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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.
Minimum Eligible Age

12 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Aspreva Pharmaceuticals

INDUSTRY

Sponsor Role collaborator

Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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Huntsville, Alabama, United States

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La Jolla, California, United States

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Los Angeles, California, United States

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San Francisco, California, United States

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San Leandro, California, United States

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Torrance, California, United States

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Miami, Florida, United States

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Atlanta, Georgia, United States

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Chicago, Illinois, United States

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Chicago, Illinois, United States

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Baltimore, Maryland, United States

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Boston, Massachusetts, United States

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Ann Arbor, Michigan, United States

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Columbia, Missouri, United States

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Brooklyn, New York, United States

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Lake Success, New York, United States

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New York, New York, United States

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New York, New York, United States

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New York, New York, United States

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Chapel Hill, North Carolina, United States

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Durham, North Carolina, United States

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Cleveland, Ohio, United States

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Columbus, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Charleston, South Carolina, United States

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Dallas, Texas, United States

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Buenos Aires, , Argentina

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Buenos Aires, , Argentina

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Córdoba, , Argentina

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San Isidro, , Argentina

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San Miguel de Tucumán, , Argentina

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Adelaide, , Australia

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Camperdown, , Australia

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Melbourne, , Australia

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Parkville, , Australia

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Woodville, , Australia

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Brussels, , Belgium

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Leuven, , Belgium

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Liège, , Belgium

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Rio de Janeiro, , Brazil

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São Paulo, , Brazil

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Sorocaba, , Brazil

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Vancouver, British Columbia, Canada

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Victoria, British Columbia, Canada

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Halifax, Nova Scotia, Canada

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London, Ontario, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Beijing, , China

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Guangdong, , China

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Guangzhou, , China

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Jiangsu, , China

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Shanghai, , China

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Brno, , Czechia

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Prague, , Czechia

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Lille, , France

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Lyon, , France

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Nantes, , France

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Paris, , France

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Paris, , France

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Toulouse, , France

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Aachen, , Germany

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Bad Bramstedt, , Germany

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Berlin, , Germany

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Berlin, , Germany

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Dresden, , Germany

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Düsseldorf, , Germany

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Erlangen, , Germany

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Hanover, , Germany

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Leipzig, , Germany

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München, , Germany

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München, , Germany

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Münster, , Germany

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Athens, , Greece

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Athens, , Greece

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Heraklion, , Greece

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Debrecen, , Hungary

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Pécs, , Hungary

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Szeged, , Hungary

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Brescia, , Italy

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Milan, , Italy

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Padua, , Italy

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Pisa, , Italy

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Udine, , Italy

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Mexico City, , Mexico

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Mérida, , Mexico

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San Luis Potosí City, , Mexico

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Lisbon, , Portugal

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Porto, , Portugal

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Alicante, , Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Madrid, , Spain

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Málaga, , Spain

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Santander, , Spain

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Seville, , Spain

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Birmingham, , United Kingdom

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Cambridge, , United Kingdom

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Leeds, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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Manchester, , United Kingdom

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Newcastle upon Tyne, , United Kingdom

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Sheffield, , United Kingdom

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Southampton, , United Kingdom

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Countries

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Costa Rica Malaysia South Africa United States Argentina Australia Belgium Brazil Canada China Czechia France Germany Greece Hungary Italy Mexico Portugal Spain United Kingdom

References

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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.

Reference Type DERIVED
PMID: 22922564 (View on PubMed)

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.

Reference Type DERIVED
PMID: 22087680 (View on PubMed)

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.

Reference Type DERIVED
PMID: 21080348 (View on PubMed)

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.

Reference Type DERIVED
PMID: 20039429 (View on PubMed)

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.

Reference Type DERIVED
PMID: 19933596 (View on PubMed)

Other Identifiers

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WX17801

Identifier Type: -

Identifier Source: org_study_id

NCT00121082

Identifier Type: -

Identifier Source: nct_alias