A Study to Evaluate Efficacy of CellCept (Mycophenolate Mofetil) in Patients With Lupus Nephritis

A Study to Evaluate the Efficacy of CellCept, Administered in a Sequential Treatment Scheme, in Delaying Progressive Renal Damage in Patients With Lupus Nephritis

This study will compare the efficacy of CellCept [0.5-2 grams per day (g/day) orally (p.o.)] and cyclophosphamide [0.5-1 grams per square meter (g/m2) quarterly] as maintenance treatment for patients with lupus nephritis. All patients will receive induction treatment with cyclophosphamide (0.5-1g/m2 monthly) for 6 months, and will then be randomized to the maintenance phase of the study for a further 6 months, followed by 6 months of treatment-free follow-up. The anticipated time on study treatment is 12 months.

Study Overview

• Status: Terminated
• Conditions: Lupus Nephritis
• Intervention / Treatment: Drug: Mycophenolate mofetil (MMF); Drug: Cyclophosphamide, Induction Phase; Drug: Prednisone; Drug: Cyclophosphamide, Maintenance Phase

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 3

Contacts and Locations

Study Locations

• Venezuela
  • Barquisimeto, Venezuela, 3005
  • Caracas, Venezuela, 1040

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• adult patients >=18 years of age;
• diagnosis of systemic lupus erythematosus and lupus nephritis (class III, IV or V).

Exclusion Criteria:

• patients who have received cytotoxic drugs in previous 8 weeks;
• systemic infections;
• hepatitis B or C, or HIV.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MMF, Prednisone; Induction Phase (Months 1 through 6): Participants received cyclophosphamide, 0.5 to (-) 1 grams per square meter (g/m^2), intravenously (IV) pulse once per month. Participants also received prednisone, 1 milligram per kilogram per day (mg/kg/day), orally (PO); the dose was reduced by 5 mg/day to a final dose of 10 mg/day. Maintenance Phase (Months 7 through 12): Participants received mycophenolate mofetil (MMF), 1 g/day, PO, twice daily (BID) for 2 weeks; 1.5 g/day, PO, three times daily (TID) for the next 2 weeks; 2 g/day, PO, BID for the remainder of the Maintenance Phase. Participants also received prednisone, as in the Induction Phase.	Drug: Mycophenolate mofetil (MMF); 1 g/day, PO BID for 2 weeks; 1.5 g/day PO TID for the next 2 weeks; and 2 g/day PO BID for the remainder of the Maintenance Phase.; Other Names: CellCept; Drug: Cyclophosphamide, Induction Phase; 0.5 - 1 g/m^2 IV pulse once per month; Drug: Prednisone; 1 mg/kg PO once per day; reduced by 5 mg every 2 weeks up to 20 mg/day; followed by a reduction of 2.5 mg every 2 weeks until reaching the maintenance phase of 10 mg/day.
Active Comparator: Maintenance Cyclophosphamide, Prednisone; Induction Phase (Months 1 through 6): Participants received cyclophosphamide, 0.5 - 1 g/m^2, IV, pulse once per month. Participants also received prednisone, 1 mg/kg/day), PO; the dose was reduced by 5 mg/day to a final dose of 10 mg/day. Maintenance Phase (Months 7 through 12): Participants received cyclophosphamide, 0.5-1 g/m^2, IV, pulse once every 3 months. Participants also received prednisone, as in the Induction Phase.	Drug: Cyclophosphamide, Induction Phase; 0.5 - 1 g/m^2 IV pulse once per month; Drug: Prednisone; 1 mg/kg PO once per day; reduced by 5 mg every 2 weeks up to 20 mg/day; followed by a reduction of 2.5 mg every 2 weeks until reaching the maintenance phase of 10 mg/day.; Drug: Cyclophosphamide, Maintenance Phase; 0.5-1 g/m^2 IV pulse once every 3 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Creatinine Clearance	Creatinine clearance in an indicator of kidney function. An increased level of creatinine in the blood indicates decreased kidney function. Normal adult values are 97 to 137 milliliters per minute (mL/min) for males and 88 to 128 mL/min for females.	18 months
Urinary Protein	Protein in urine is an indicator of kidney function. An increased urinary protein level indicates decreased kidney function. Normal values are approximately 0 to 8 milligrams per deciliter (mg/dL).	18 months
Serum Creatinine	Serum creatinine is an indicator of kidney function. Creatinine is a substance formed from the metabolism of creatine, commonly found in blood, urine, and muscle tissue. It is removed from the blood by the kidneys and excreted in urine. An increased level of creatinine in the blood indicates decreased kidney function. Normal adult blood levels of creatinine are 0.5 to 1.1 mg/dL for females and 0.6 to 1.2 mg/dL for males, however the normal values are age-dependent as elderly participants typically have smaller muscle mass.	18 months
Serum Albumin	Albumin is a protein made by the liver. A serum albumin test measures the amount of this protein in the clear liquid portion of the blood. Decreased serum albumin levels can be an indicator of liver and/or kidney disease, The normal range is 3.4 - 5.4 grams (g)/dL.	18 months

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: March 1, 2006
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: March 5, 2014
• First Submitted That Met QC Criteria: March 6, 2014
• First Posted (Estimate): March 7, 2014

Study Record Updates

• Last Update Posted (Estimate): July 17, 2014
• Last Update Submitted That Met QC Criteria: June 17, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Kidney Diseases; Urologic Diseases; Connective Tissue Diseases; Glomerulonephritis; Lupus Erythematosus, Systemic; Nephritis; Lupus Nephritis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Cyclophosphamide; Prednisone; Mycophenolic Acid
• Other Study ID Numbers: ML18989