Clinical Trial: Efficacy and Safety of Enteric-coated Mycophenolate Sodium in Combination With Two Corticosteroid Regimens for the Treatment of Lupus Nephritis Flare

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Randomized, Multicenter, Open-label, 6-month Study to Explore the Efficacy and Safety of Enteric-coated Mycophenolate Sodium in Combination With Two Corticosteroid Regimens for the Treatment of

Brief Summary: The study will investigate the efficacy and safety of enteric-coated mycophenolate sodium in combination with two different corticosteroid (CS) regimes for the induction of remission of a lupus nephritis flare. Patients will be randomly allocated to standard CS regimen (group I) or to a reduced dose CS regimen (group II)

Detailed Summary:
Sponsor: Novartis Pharmaceuticals

Current Primary Outcome: Number of Patients With Complete Remission [ Time Frame: 24 Weeks ]

Original Primary Outcome:

• Assess poportion of pts in complete
• remission after 24 wks of treatment study treatment groups:
• EC-MPS administered at a dose of 2,160 mg/day in
• combination with reduced corticosteroid (CS)
• regimen compared to the combination with stand

Current Secondary Outcome:

• Number of Patients With Complete Remission [ Time Frame: 12 Weeks ]
  Complete remission was defined as urine protein/urine creatinine ratio < 0.5 gram urine protein per gram urine creatinine, urine sediment normalized (no cellular casts, < 5 red cells per high power field), and serum creatinine within 10% of normal value.
• Number of Patients With Partial Remission [ Time Frame: Baseline to 12 and 24 weeks ]
  Partial remission was defined as urine protein/creatinine ratio reduced by at least 50% from baseline and stable serum creatinine within 10% of baseline value) or improved.
• Cumulative Dose of Prednisone Equivalent Corticosteroids (CS) [ Time Frame: 12 Weeks and 24 Weeks ]
  Corticosteroid use was measured as cumulative dose until 12 and 24 weeks of treatment as well as daily doses at baseline, 12 and 24 weeks.
• Number of Patients With Moderate to Severe Flares [ Time Frame: 12 and 24 weeks ]
  A moderate to severe flare was defined as the occurrence of increased lupus activity after partial or complete remission, based on the presence of 1 BILAG A score or >=3 BILAG B scores. British Isles Lupus Assessment Group (BILAG) index divides lupus activity in 8 organs/systems which are each given a score of A to E. A=disease sufficiently active to need disease modifying treatment; B=problems requiring symptomatic treatment; C=mild stable disease; D=previously affected but currently inactive system; E=the system or organ has never been involved. BILAG score: A=9, B=3, C=1, D/E=0; range(0-72)
• Duration of Exposure to Study Medication [ Time Frame: 24 weeks ]
  The duration of exposure was calculated as the date of the last Mycophenolate sodium dose minus the date of the last Mycophenolate sodium dose +1.
• Number of Patients With Adverse Events and Infections [ Time Frame: 24 weeks ]
  Safety assessments included collecting all adverse events (AEs), serious adverse events (SAEs), with their severity and relationship to study drug. According to FDA 21CFR 314.80, a serious adverse event (SAE) is described as any adverse event that leads to death, is life threatening ( NIH criteria Grade 4), causes or prolongs hospitalization, results in a congenital anomaly, or any other important medical event not described above.
• Number of Patients With Treatment Failure [ Time Frame: 12 Weeks and 24 Weeks ]
  Treatment failure was defined as no therapeutic response (without complete or partial remission) or premature discontinuation during the first 24 weeks from study medication or the study for any reason except complete or partial remission.
• Change From Baseline in Overall Disease Activity With Systematic Lupus Erythematosus Disease Activity Index (SLEDAI) [ Time Frame: From Baseline to week 4, week 12 and week 24 ]
  SLEDAI stands for Systemic Lupus Erythematosus Disease Activity Index and was a well established global score index based on assessment of 24 items measuring a disease activity in the 10-day period prior to the assessment. SLEDAI item weights range from 1 for fever to 8 for seizures. A maximum theoretical score is 105. Total score range from 1 to 105. A flare has been defined as a SLEDAI score increase of 3 or more to a level of 8 or higher. During flares SLEDAI scores of 25 to 30 are common.
• Change From Baseline in Overall Disease Activity With British Isles Lupus Assessment Group (BILAG) [ Time Frame: From Baseline to week 4, week 12 and week 24 ]
  BILAG (British Isles Lupus Assessment Group) index divides lupus activity into 8 organs/systems and was based on the principle of the physician's intention to treat, assessing activity in the previous one month. Each organ or system was given a score of A to E, where A = disease that is sufficiently active to require disease modifying treatment; a B = problems requiring symptomatic treatment; C = stable mild disease; D = previously affected but currently inactive system; and E = the system or organ has never been involved. [A=9, B=3, C=1, D/E=0 the score range for each patient will be 0-72].

Original Secondary Outcome:

• assess proportion of patients in complete remission at 12 wks.
• assess proportion of patients with no therapeutic response at 12&24 wks.
• assess CS use as cumulative dose until 12&24 weeks of treatment as well as doses at baseline, 12&24 wks.
• assess proportion of patients with partial remission of lupus nephritis flares at wk 12&24 wks.
• evaluate overall disease activity by using BILAG (British Isles Lupus Assessment Group)
• Systematic Lupus Erythematosus Disease Activity Index (SLEDAI) activity
• indices at 4,12& 24 wks

Dates:
Date Received: January 16, 2007
Date Started: February 2007
Date Completion:
Last Updated: May 31, 2011
Last Verified: May 2011