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

This study has been terminated.
(Study was terminated early for administrative reasons.)
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00425438
First received: January 22, 2007
Last updated: September 22, 2014
Last verified: September 2014
  Purpose

This 2 arm study will compare the efficacy and safety of CellCept plus corticosteroids, versus cyclophosphamide plus corticosteroids in the induction phase followed by azathioprine in the maintenance phase, in maintaining remission and renal function in patients with lupus nephritis. Patients will be randomized to receive CellCept 1g bid po plus corticosteroids for 24 weeks, followed by CellCept 0.75g bid po plus corticosteroids for the following 24 weeks, or cyclophosphamide 0.5-1.0g/m2 monthly plus corticosteroids for 24 weeks, followed by azathioprine 2mg/kg/day po plus corticosteroids for the following 24 weeks. Response rate will be assessed at the end of the induction phase, and at the end of study. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.


Condition Intervention Phase
Lupus Nephritis
Drug: Mycophenolate Mofetil
Drug: Corticosteroids
Drug: Azathioprine
Drug: Cyclophosphamide
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Open-label Study to Compare the Effect of CellCept Plus Corticosteroids, and Cyclophosphamide Plus Corticosteroids Followed by Azathioprine, on Remission Rate in Patients With Lupus Nephritis

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Complete Response (CR) by the End of Treatment - Percentage of Participants With an Event [ Time Frame: Screening, Day 0, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48 ] [ Designated as safety issue: No ]
    CR was defined as a urinary protein value of less than (<) 500 mg per 24 hours (mg/24h) and no hematuria or cellular casts in the urine, and a stable serum creatinine value within the range of plus or minus (±) 25 percent (%) of baseline (BL) or some improvement.


Secondary Outcome Measures:
  • Complete Response [ Time Frame: Screening, Day 0, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48 ] [ Designated as safety issue: No ]
    The median time, in months, to CR was defined as the time from randomization to CR event.

  • Percentage of Participants With Treatment Response Event by End of Treatment [ Time Frame: Screening, Day 0, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48 ] [ Designated as safety issue: No ]
    Treatment response was defined by a reduction in the ratio of urine protein to creatinine to <3 mg/mg for participants with nephrotic proteinuria and a decrease of more than 50% in their urine protein to creatinine value from BL for participants with non-nephrotic proteinuria; a stable serum creatinine value or an increase of more than 30% from BL; and having not received IV prednisone after Week 28.

  • Percentage of Participants With a Decrease of 25% or 50% in Glomerular Filtration Rate (GFR) [ Time Frame: Screening, Day 0, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48 ] [ Designated as safety issue: No ]
    GFR was calculated according to the simplified modification of diet in renal disease (MDRD) formula.

  • Percentage of Participants Terminating Treatment [ Time Frame: Screening, Day 0, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48 ] [ Designated as safety issue: No ]
  • Time to Treatment Failure [ Time Frame: Screening, Day 0, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48 ] [ Designated as safety issue: No ]
    Treatment failure was defined as the occurrence of any of the following: death; chronic renal failure requiring dialysis or kidney transplantation; an increase in average serum creatinine values by 2-fold for 2 consecutive measures from BL, and a increase by 2-fold for 2 consecutive measures in at least 4 weeks; recurrent kidney disease defined by, proteinuria, a doubling in the ratio of urine protein to creatinine from BL and a urinary protein value of <0.5 g/24h or greater than (>) 1 g/24h or >0.5 g/24h or >2 g/24h at Week 24, kidney disease, defined by an increase in serum creatinine of 25% from BL along with a doubling of urinary protein of at least 2 g/24h, and hematuria, 2 or more blood cells per urine dipstick test.


Enrollment: 52
Study Start Date: March 2007
Study Completion Date: April 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Mycophenolate Mofetil
Participants received mycophenolate mofetil (MMF) 0.5 grams (g), orally (PO), twice daily (BID) from Day 0 to the end of Week 1, followed by 1.0 g, PO, BID from Weeks 2 through 24, and 0.75 g, PO, BID from Weeks 32 to 48. Participants also received prednisolone 0.75 to 1.0 milligrams per kilogram (mg/kg), PO, once per day, up to a maximum of 60 mg per day from Weeks 1 through 4, reduced by 10 mg per day every 2 weeks until dose reaches 40 mg per day, followed by a reduction of 5 mg per day every 2 weeks until dose reaches 10 mg per day up to Week 48.
Drug: Mycophenolate Mofetil
0.5 g PO BID from Day 0 to the end of Week 1, followed by 1.0 g PO BID from Weeks 2 through 24, and 0.75 g PO BID from Weeks 32 to 48
Other Name: CellCept
Drug: Corticosteroids
0.75 to 1.0 mg/kg/d PO (up to 60 kg/day) from Weeks 1 through 4; reduced by 10 mg/day every 2 weeks until dose reaches 40 mg/day, followed by a reduction of 5 mg/day every 2 weeks until dose reaches 10 mg/day up to Week 48
Other Name: Prednisolone
Active Comparator: Cyclophosphamide/Azathioprine
Participants received cyclophosphamide 0.75 grams per square meter (g/m^2), intravenously (IV), every 4 weeks from Weeks 1 through 4, and 0.5 to (-) 1.0 g/m^2, IV, to maintain a minimum white blood cell (WBC) count of greater than or equal to (≥) 2500 per cubic millimeter (mm^3) every 4 weeks from Weeks 5 through 24. Participants also received azathioprine 100 mg, PO, daily for participants with a body weight of 50 to 70 kg and 150 mg, PO, daily for subjects with a body weight of more than 70 kg from Weeks 25 through 48. Participants also received prednisolone 0.75 to 1.0 mg/kg, PO, once per day, up to a maximum of 60 mg per day from Weeks 1 through 4, reduced by 10 mg per day every 2 weeks until dose reaches 40 mg per day, followed by a reduction of 5 mg per day every 2 weeks until dose reaches 10 mg per day up to Week 48.
Drug: Corticosteroids
0.75 to 1.0 mg/kg/d PO (up to 60 kg/day) from Weeks 1 through 4; reduced by 10 mg/day every 2 weeks until dose reaches 40 mg/day, followed by a reduction of 5 mg/day every 2 weeks until dose reaches 10 mg/day up to Week 48
Other Name: Prednisolone
Drug: Azathioprine
100 mg PO daily for participants with a body weight of 50 to 70 kg,150 mg PO daily for subjects with a body weight of more than 70 kg up to Week 48
Drug: Cyclophosphamide
0.75 g/m^2 IV every 4 weeks from Weeks 1 through 4, and 0.5-1.0 g/m^2 to maintain a minimum WBC count of ≥ 2500 per mm^3 from Weeks 5 through 24

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • adult patients, 18-75 years of age;
  • systemic lupus erythematosus;
  • histological diagnosis of lupus nephritis.

Exclusion Criteria:

  • not in need of immunosuppressive treatment (in addition to corticosteroids);
  • continuous dialysis starting >2 weeks before randomization, with an anticipated duration of >8 weeks;
  • previous or planned kidney transplant.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00425438

Locations
China
Beijing, China, 100029
Beijing, China, 100005
Beijing, China, 100853
Guangzhou, China, 510080
Guangzhou, China, 510515
Hangzhou, China, 310003
Nanjing, China, 210008
Shanghai, China, 200025
Shanghai, China, 200001
Shanghai, China, 200003
Shenyang, China, 110001
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00425438     History of Changes
Other Study ID Numbers: ML19978
Study First Received: January 22, 2007
Results First Received: August 14, 2014
Last Updated: September 22, 2014
Health Authority: China: Food and Drug Administration

Additional relevant MeSH terms:
Lupus Nephritis
Nephritis
Autoimmune Diseases
Connective Tissue Diseases
Glomerulonephritis
Immune System Diseases
Kidney Diseases
Lupus Erythematosus, Systemic
Urologic Diseases
Azathioprine
Cyclophosphamide
Mycophenolate mofetil
Mycophenolic Acid
Prednisolone
Alkylating Agents
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antirheumatic Agents
Enzyme Inhibitors
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 23, 2014