Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00377637




Registration number
NCT00377637
Ethics application status
Date submitted
15/09/2006
Date registered
18/09/2006
Date last updated
6/12/2011

Titles & IDs
Public title
A Study of Mycophenolate Mofetil (CellCept) in Management of Patients With Lupus Nephritis.
Scientific 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.
Secondary ID [1] 0 0
WX17801
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lupus Nephritis 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Mycophenolate mofetil (MMF)
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Azathioprine
Treatment: Drugs - Placebo to Azathioprine
Treatment: Drugs - Placebo to Mycophenolate mofetil
Treatment: Drugs - Corticosteroid

Experimental: 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.

Active comparator: 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.

Experimental: 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.

Active comparator: 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.


Treatment: Drugs: 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.

Treatment: Drugs: 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.

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

Treatment: Drugs: Placebo to Azathioprine
Placebo capsules matching Azathioprine taken orally once a day.

Treatment: Drugs: Placebo to Mycophenolate mofetil
Placebo tablets matching Mycophenolate mofetil taken orally twice daily.

Treatment: Drugs: 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 code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Induction Phase: Number of Patients Showing Treatment Response
Timepoint [1] 0 0
24 weeks
Primary outcome [2] 0 0
Maintenance Phase: Kaplan-Meier Estimates of Percentage of Participants Treatment Failure Free, by Time Interval
Timepoint [2] 0 0
From the start of the Maintenance Phase to Month 36
Secondary outcome [1] 0 0
Induction Phase: Number of Participants Achieving Complete Remission
Timepoint [1] 0 0
24 weeks
Secondary outcome [2] 0 0
Induction Phase: Change From Baseline to Week 24 in Serum Creatinine
Timepoint [2] 0 0
Baseline, Week 24
Secondary outcome [3] 0 0
Induction Phase: Change From Baseline to Week 24 in 24-hour Urine Protein
Timepoint [3] 0 0
Baseline, Week 24
Secondary outcome [4] 0 0
Induction Phase: Change From Baseline to Week 24 in Serum Albumin
Timepoint [4] 0 0
Baseline, Week 24
Secondary outcome [5] 0 0
Induction Phase: Change in Renal British Isles Lupus Assessment Group (BILAG) Score
Timepoint [5] 0 0
Baseline, 24 weeks
Secondary outcome [6] 0 0
Induction Phase: Change From Baseline in Short-Form Health Survey (SF-36) Domain and Component Scores
Timepoint [6] 0 0
Baseline and 24 weeks
Secondary outcome [7] 0 0
Maintenance Phase: Events Contributing to the Primary Endpoint: Number of Deaths
Timepoint [7] 0 0
From the start of the Maintenance Phase to Month 36
Secondary outcome [8] 0 0
Maintenance Phase: Events Contributing to the Primary Endpoint: Number of Participants With End-stage Renal Disease (ESRD)
Timepoint [8] 0 0
From the start of the Maintenance Phase to Month 36
Secondary outcome [9] 0 0
Maintenance Phase: Events Contributing to the Primary Endpoint: Number of Participants With Sustained Doubling of Serum Creatinine
Timepoint [9] 0 0
From the start of the Maintenance Phase to Month 36
Secondary outcome [10] 0 0
Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Renal Flare Free, by Time Interval
Timepoint [10] 0 0
From the start of the Maintenance Phase to Month 36
Secondary outcome [11] 0 0
Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Not Receiving Rescue Therapy
Timepoint [11] 0 0
From the start of the Maintenance Phase to Month 36
Secondary outcome [12] 0 0
Maintenance Phase: Participants With Major Extra-renal Flare
Timepoint [12] 0 0
From the start of the Maintenance Phase to Month 36

Eligibility
Key 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.
Minimum age
12 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/07/2005
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/03/2010
Sample size
Target
Accrual to date
Final
370
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Adelaide
Recruitment hospital [2] 0 0
- Camperdown
Recruitment hospital [3] 0 0
- Melbourne
Recruitment hospital [4] 0 0
- Parkville
Recruitment hospital [5] 0 0
- Woodville
Recruitment postcode(s) [1] 0 0
SA 5000 - Adelaide
Recruitment postcode(s) [2] 0 0
2050 - Camperdown
Recruitment postcode(s) [3] 0 0
3168 - Melbourne
Recruitment postcode(s) [4] 0 0
3052 - Parkville
Recruitment postcode(s) [5] 0 0
5011 - Woodville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
North Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Ohio
Country [13] 0 0
United States of America
State/province [13] 0 0
Oklahoma
Country [14] 0 0
United States of America
State/province [14] 0 0
Pennsylvania
Country [15] 0 0
United States of America
State/province [15] 0 0
South Carolina
Country [16] 0 0
United States of America
State/province [16] 0 0
Texas
Country [17] 0 0
Argentina
State/province [17] 0 0
Buenos Aires
Country [18] 0 0
Argentina
State/province [18] 0 0
Córdoba
Country [19] 0 0
Argentina
State/province [19] 0 0
San Isidro
Country [20] 0 0
Argentina
State/province [20] 0 0
Tucuman
Country [21] 0 0
Belgium
State/province [21] 0 0
Bruxelles
Country [22] 0 0
Belgium
State/province [22] 0 0
Leuven
Country [23] 0 0
Belgium
State/province [23] 0 0
Liege
Country [24] 0 0
Brazil
State/province [24] 0 0
Rio de Janeiro
Country [25] 0 0
Brazil
State/province [25] 0 0
Sao Paulo
Country [26] 0 0
Brazil
State/province [26] 0 0
Sorocaba
Country [27] 0 0
Canada
State/province [27] 0 0
British Columbia
Country [28] 0 0
Canada
State/province [28] 0 0
Nova Scotia
Country [29] 0 0
Canada
State/province [29] 0 0
Ontario
Country [30] 0 0
Canada
State/province [30] 0 0
Quebec
Country [31] 0 0
China
State/province [31] 0 0
Beijing
Country [32] 0 0
China
State/province [32] 0 0
Guangdong
Country [33] 0 0
China
State/province [33] 0 0
Guangzhou
Country [34] 0 0
China
State/province [34] 0 0
Jiangsu
Country [35] 0 0
China
State/province [35] 0 0
Shanghai
Country [36] 0 0
Czech Republic
State/province [36] 0 0
Brno
Country [37] 0 0
Czech Republic
State/province [37] 0 0
Praha 2
Country [38] 0 0
France
State/province [38] 0 0
Lille
Country [39] 0 0
France
State/province [39] 0 0
Lyon
Country [40] 0 0
France
State/province [40] 0 0
Nantes
Country [41] 0 0
France
State/province [41] 0 0
Paris
Country [42] 0 0
France
State/province [42] 0 0
Toulouse
Country [43] 0 0
Germany
State/province [43] 0 0
Aachen
Country [44] 0 0
Germany
State/province [44] 0 0
Bad Bramstedt
Country [45] 0 0
Germany
State/province [45] 0 0
Berlin
Country [46] 0 0
Germany
State/province [46] 0 0
Dresden
Country [47] 0 0
Germany
State/province [47] 0 0
Düsseldorf
Country [48] 0 0
Germany
State/province [48] 0 0
Erlangen
Country [49] 0 0
Germany
State/province [49] 0 0
Hannover
Country [50] 0 0
Germany
State/province [50] 0 0
Leipzig
Country [51] 0 0
Germany
State/province [51] 0 0
Muenster
Country [52] 0 0
Germany
State/province [52] 0 0
München
Country [53] 0 0
Greece
State/province [53] 0 0
Athens
Country [54] 0 0
Greece
State/province [54] 0 0
Heraklion
Country [55] 0 0
Hungary
State/province [55] 0 0
Debrecen
Country [56] 0 0
Hungary
State/province [56] 0 0
Pécs
Country [57] 0 0
Hungary
State/province [57] 0 0
Szeged
Country [58] 0 0
Italy
State/province [58] 0 0
Brescia
Country [59] 0 0
Italy
State/province [59] 0 0
Milano
Country [60] 0 0
Italy
State/province [60] 0 0
Padova
Country [61] 0 0
Italy
State/province [61] 0 0
Pisa
Country [62] 0 0
Italy
State/province [62] 0 0
Udine
Country [63] 0 0
Mexico
State/province [63] 0 0
Merida
Country [64] 0 0
Mexico
State/province [64] 0 0
Mexico City
Country [65] 0 0
Mexico
State/province [65] 0 0
San Luis Potosi
Country [66] 0 0
Portugal
State/province [66] 0 0
Lisboa
Country [67] 0 0
Portugal
State/province [67] 0 0
Porto
Country [68] 0 0
Spain
State/province [68] 0 0
Alicante
Country [69] 0 0
Spain
State/province [69] 0 0
Barcelona
Country [70] 0 0
Spain
State/province [70] 0 0
Madrid
Country [71] 0 0
Spain
State/province [71] 0 0
Malaga
Country [72] 0 0
Spain
State/province [72] 0 0
Santander
Country [73] 0 0
Spain
State/province [73] 0 0
Sevilla
Country [74] 0 0
United Kingdom
State/province [74] 0 0
Birmingham
Country [75] 0 0
United Kingdom
State/province [75] 0 0
Cambridge
Country [76] 0 0
United Kingdom
State/province [76] 0 0
Leeds
Country [77] 0 0
United Kingdom
State/province [77] 0 0
London
Country [78] 0 0
United Kingdom
State/province [78] 0 0
Manchester
Country [79] 0 0
United Kingdom
State/province [79] 0 0
Newcastle Upon Tyne
Country [80] 0 0
United Kingdom
State/province [80] 0 0
Sheffield
Country [81] 0 0
United Kingdom
State/province [81] 0 0
Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Aspreva Pharmaceuticals
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/study/NCT00377637
Trial related presentations / publications
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.
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.
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.
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. Erratum In: Arthritis Rheum. 2010 Oct;62(10):3005.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00377637