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

This study has been completed.

Study NCT00377637 Information provided by Hoffmann-La Roche

First Received on September 15, 2006. Last Updated on October 31, 2011 History of Changes

Results First Received: August 11, 2011

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Lupus Nephritis
Interventions:	Drug: Mycophenolate mofetil (MMF) Drug: Cyclophosphamide Drug: Azathioprine Drug: Placebo to Azathioprine Drug: Placebo to Mycophenolate mofetil Drug: Corticosteroid

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The induction phase was a prospective, randomized, open-label, active controlled, parallel group, international multicenter, 2-arm comparison study of MMF versus IVC in inducing a response in patients with Lupus nephritis. Responders in the induction phase were re-randomized into a double-blind, double-dummy, active controlled Maintenance Phase.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups

	Description
Induction Phase: Cyclophosphamide	Participants received monthly intravenous 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.
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.
Maintenance Phase: Mycophenolate Mofetil	Participants who responded to Induction Phase treatment 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	Participants who responded to Induction Phase treatment 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.

Participant Flow for 2 periods

Period 1: Induction Phase

	Induction Phase: Cyclophosphamide	Induction Phase: Mycophenolate Mofetil
STARTED	185 ^[1]	185 ^[1]
Safety Population	180	184
COMPLETED	156	150
NOT COMPLETED	29	35
Adverse Event	12	21
Deterioration/serum creatinine	2	0
Dose reduction of MMF < 2 g/day for 14 d	0	1
Lost to Follow-up	2	1
Death	1	3
Withdrawal by Subject	5	6
Physician Decision	3	1
Sponsor decision	1	2
Non-Compliance	1	0
Reason for withdrawal is not noted	2	0

[1]	Intent-To-Treat

Period 2: Maintenance Phase

	Maintenance Phase: Mycophenolate Mofetil	Maintenance Phase: Azathioprine
STARTED	116	111
COMPLETED	73	54
NOT COMPLETED	43	57
Adverse Event	29	43
Physician Decision	5	4
Lost to Follow-up	3	1
Withdrawal by Subject	3	3
Sponsor decision	2	3
Non-compliance	1	1
Study medication stopped > 14 days	0	1
Death	0	1

Baseline Characteristics

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Reporting Groups

	Description
Induction Phase: Cyclophosphamide	Participants received monthly intravenous 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.
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.
Maintenance Phase: Mycophenolate Mofetil	Participants who responded to Induction Phase treatment 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	Participants who responded to Induction Phase treatment 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.

Baseline Measures

	Induction Phase: Cyclophosphamide	Induction Phase: Mycophenolate Mofetil	Maintenance Phase: Mycophenolate Mofetil	Maintenance Phase: Azathioprine	Total
Number of Participants [units: participants]	185	185	116	111	597
Age, Customized [units: years] Mean ± Standard Deviation
Induction Phase	31.3 ± 10.25	32.4 ± 11.7	NA ± NA ^[1]	NA ± NA ^[1]	31.9 ± 10.72
Maintenance Phase	NA ± NA ^[2]	NA ± NA ^[2]	31.8 ± 10.59	31.0 ± 10.77	31.4 ± 10.65
Gender, Customized [units: Participants]
Induction Phase - Female	156	157	0	0	313
Induction Phase - Male	29	28	0	0	57
Maintenance Phase - Female	0	0	99	96	195
Maintenance Phase - Male	0	0	17	15	32

[1]	Did not participate in the Induction Phase. Please see Maintenance Phase.
[2]	Did not participate in the Maintenance Phase. Please see Induction Phase.

Outcome Measures

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1. Primary:

Induction Phase: Number of Patients Showing Treatment Response [ Time Frame: 24 weeks ]

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2. Primary:

Maintenance Phase: Kaplan-Meier Estimates of Percentage of Participants Treatment Failure Free, by Time Interval [ Time Frame: From the start of the Maintenance Phase to Month 36 ]

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3. Secondary:

Induction Phase: Number of Participants Achieving Complete Remission [ Time Frame: 24 weeks ]

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4. Secondary:

Induction Phase: Change From Baseline to Week 24 in Serum Creatinine [ Time Frame: Baseline, Week 24 ]

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5. Secondary:

Induction Phase: Change From Baseline to Week 24 in 24-hour Urine Protein [ Time Frame: Baseline, Week 24 ]

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6. Secondary:

Induction Phase: Change From Baseline to Week 24 in Serum Albumin [ Time Frame: Baseline, Week 24 ]

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7. Secondary:

Induction Phase: Change in Renal British Isles Lupus Assessment Group (BILAG) Score [ Time Frame: Baseline, 24 weeks ]

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8. Secondary:

Induction Phase: Change From Baseline in Short-Form Health Survey (SF-36) Domain and Component Scores [ Time Frame: Baseline and 24 weeks ]

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9. Secondary:

Maintenance Phase: Events Contributing to the Primary Endpoint: Number of Deaths [ Time Frame: From the start of the Maintenance Phase to Month 36 ]

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10. Secondary:

Maintenance Phase: Events Contributing to the Primary Endpoint: Number of Participants With End-stage Renal Disease (ESRD) [ Time Frame: From the start of the Maintenance Phase to Month 36 ]

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11. Secondary:

Maintenance Phase: Events Contributing to the Primary Endpoint: Number of Participants With Sustained Doubling of Serum Creatinine [ Time Frame: From the start of the Maintenance Phase to Month 36 ]

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12. Secondary:

Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Renal Flare Free, by Time Interval [ Time Frame: From the start of the Maintenance Phase to Month 36 ]

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13. Secondary:

Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Not Receiving Rescue Therapy [ Time Frame: From the start of the Maintenance Phase to Month 36 ]

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14. Secondary:

Maintenance Phase: Participants With Major Extra-renal Flare [ Time Frame: From the start of the Maintenance Phase to Month 36 ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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:

Name/Title: Medical Communications
Organization: Hoffman-LaRoche
phone: 800-821-8590

No publications provided by Hoffmann-La Roche

Publications automatically indexed to this study:

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.

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.

Isenberg D, Appel GB, Contreras G, Dooley MA, Ginzler EM, Jayne D, Sánchez-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. Epub 2009 Nov 20.

Responsible Party:	Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT00377637 History of Changes
Obsolete Identifiers:	NCT00121082
Other Study ID Numbers:	WX17801
Study First Received:	September 15, 2006
Results First Received:	August 11, 2011
Last Updated:	October 31, 2011
Health Authority:	United States: Food and Drug Administration