The purpose of this study is to provide further information on the effect of mycophenolate mofetil (MMF) in the initial treatment of lupus nephritis (induction phase) and to assess how well it maintains this effect over longer periods (maintenance phase), when compared to the current standard treatments. The safety of MMF in the long-term treatment of lupus nephritis will also be assessed.

Condition	Intervention	Phase
Lupus Nephritis	Drug: Mycophenolate mofetil  Drug: Intravenous cyclophosphamide (active comparator, induction)  Drug: Azathioprine (active comparator, maintenance)	Phase III

Further Study Details: 

Primary Outcomes: Response (induction); Treatment failure (maintenance)
Secondary Outcomes: Induction: Complete remission, Partial remission, Extra-renal remission, Disease activity scales, Complement, anti-dsDNA.; Maintenance: Components of treatment failure, Achievement of complete renal remission, Combined renal and extrarenal remission; Safety
Expected Total Enrollment:  358

(Induction Phase): Eligible subjects will be randomized to receive open-label induction therapy of MMF for 24 weeks or six 4-weekly doses of IVC. All subjects will receive concomitant corticosteroid therapy consisting of oral prednisolone (or equivalent), tapered according to a protocol-defined schedule. At the end of the induction phase, subjects will be assessed for response.

(Maintenance Phase): Subjects with response will be re-randomized to receive double-blind, double-dummy maintenance treatment with MMF or azathioprine (each with corticosteroids), and will be followed until treatment failure. Treatment failure is a composite endpoint, comprising renal and non-renal parameters. The maintenance phase will continue for approximately 36 months.

Ages Eligible for Study:  12 Years   -   75 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Diagnosis of SLE
• Kidney biopsy within the 6 months prior to first randomization with a histologic diagnosis of lupus nephritis classes III, IV-S or IV-G, (A) or (A/C); or class V
• Laboratory evidence of active nephritis at screening. For Class IV-S or IV-G: proteinuria ≥1000 mg/24 h or serum creatinine above 1.3 mg/dL (115 umol/L) or active urinary sediment. For Class III or V: proteinuria ≥ 2000 mg/24 h or serum creatinine above 1.3 mg/dL (115 umol/L)

Exclusion Criteria:

• In the opinion of the investigator, does not require long-term immunosuppressive treatment (in addition to corticosteroids)
• Known hypersensitivity or contraindication to MMF, mycophenolic acid (MPA), cyclophosphamide, azathioprine, corticosteroids or any components of these drug products
• Pregnancy, nursing (breastfeeding) or use of a non-reliable method of contraception
• Dialysis starting more than 2 weeks before randomization, and/or expected to continue more than 8 weeks
• Previous kidney transplant or planned transplant
• Presence or history of: pancreatitis or GI hemorrhage within 6 months; active unhealed peptic ulcer within 3 months; congenital or acquired immunodeficiency; malignancy within 5 years, except basal cell carcinoma; lymphoproliferative disease or previous total lymphoid irradiation; severe viral infection.
• Other known clinically significant active medical conditions

Please refer to this study by ClinicalTrials.gov identifier  NCT00121082

Laura Lisk (Aspreva)      44 1276 853600    llisk@aspreva.com

Canada, British Columbia
      For information about recruitment in North America, Latin America contact Jan North at Aspreva Pharmaceuticals., Victoria,  British Columbia,  Canada; Recruiting
United Kingdom, Surrey
      For information about recruitment in Europe and the rest of the world please contact Laura Lisk, Bagshot,  Surrey,  United Kingdom; Recruiting

Study chairs or principal investigators

Neil Solomons, MD,  Aspreva Pharmaceuticals   

Study ID Numbers:  WX17801
Record last reviewed:  July 2005
Last Updated:  July 25, 2005
Record first received:  July 20, 2005
ClinicalTrials.gov Identifier:  NCT00121082
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-07-26