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

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00423098
First received: January 16, 2007
Last updated: May 31, 2011
Last verified: May 2011
  Purpose

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)


Condition Intervention Phase
Lupus Nephritis
Drug: Mycophenolate sodium
Drug: Prednisone
Drug: Methylprednisolone
Phase 2

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, 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 Lupus Nephritis Flare

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Number of Patients With Complete Remission [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
    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 range according to local lab.


Secondary Outcome Measures:
  • Number of Patients With Complete Remission [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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].


Enrollment: 81
Study Start Date: February 2007
Study Completion Date: November 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Standard dose
Mycophenolate sodium was administered orally in combination with a standard dose of corticosteroids (CS) administered as prednisone or prednisone equivalent (PRED). Mycophenolate sodium was administered in divided doses at a daily dose of 1440 mg during the first 2 weeks of the study and then at 2160 mg daily for the next 22 weeks. The dose of Prednisone was started at 1 mg per kg body weight and subsequently tapered according to the patient's weight. The planned treatment duration was 24 weeks.
Drug: Mycophenolate sodium
Mycophenolate sodium as administered orally for 2 weeks at 1440mg daily and then increased to 2160mg daily for 22 weeks.
Other Name: Myfortic
Drug: Prednisone
Oral prednisone or prednisone equivalent was started on Day 4 and subsequently tapered every 2 weeks according to the patient's weight.
Drug: Methylprednisolone
All patients received bolus therapy with 0.5 g of intravenous Methylprednisolone per day for 3 consecutive days.
Active Comparator: Low dose
Mycophenolate sodium was administered in combination with a reduced dose of corticosteroids (CS) administered as prednisone or prednisone equivalent (PRED). Mycophenolate sodium was administered in divided doses at a daily dose of 1440 mg during the first 2 weeks of the study and then at 2160 mg daily for the next 22 weeks. The dose of Prednisone was started at 0.5 mg per kg body weight and subsequently tapered according to the patient's weight. The planned treatment duration was 24 weeks.
Drug: Mycophenolate sodium
Mycophenolate sodium as administered orally for 2 weeks at 1440mg daily and then increased to 2160mg daily for 22 weeks.
Other Name: Myfortic
Drug: Prednisone
Oral prednisone or prednisone equivalent was started on Day 4 and subsequently tapered every 2 weeks according to the patient's weight.
Drug: Methylprednisolone
All patients received bolus therapy with 0.5 g of intravenous Methylprednisolone per day for 3 consecutive days.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria

  • Male or female patients with systemic lupus erythematosus (SLE)(at least 4 classification criteria)
  • Aged ≥18 years,
  • Proliferative lupus nephritis classified as ISN/RPS class III or IV
  • Renal biopsy within the last 24-month preceding the study entry
  • Proteinuria defined as >0.5 gram urine protein per gram urine creatinine at screening and baseline
  • Clinical activity defined by one or more of the following changes in renal function: Serum creatinine >1.0 mg/dl (88.4 μmol/l)
  • Microscopic hematuria defined as >5 red cells per high power field
  • Presence of cellular casts

Exclusion criteria

  • Patients with calculated creatinine clearance <30 ml/min (using the Cockcroft-Gault formula)
  • Patients having received an intravenous (i.v.) corticosteroid bolus during the last 3 months,
  • Patients having received oral or i.v. cyclophosphamide during the last 3 month
  • Patients having received mycophenolate mofetil (MMF) within the preceding 3 months
  • Use of any antibody therapy within the past 6 months
  • Pregnant or nursing (lactating) women or women of child-bearing potential who are planning to become pregnant, or are not willing to use effective means of contraception throughout the study and during one month after the end of the study.
  • Use of other investigational drugs within 1 month of enrollment (except for antibodies: within 6 months of enrollment
  • History of hypersensitivity to any of the study drugs or to drugs with similar chemical structures,
  • History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin.

Other protocol-defined inclusion/exclusion criteria may apply.

  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: NCT00423098

Locations
Colombia
Novartis
Bogota, Colombia
France
Novartis
Creteil, France
Novartis
Nantes, France
Novartis Investigative Site
Paris, France
Germany
Novartis
Berlin, Germany
Novartis
Tubingen, Germany
Greece
Novartis
Athens, Greece
Hungary
Novartis
Budapest, Hungary
Novartis
Debrecen, Hungary
Italy
Novartis
Brescia, Italy
Novartis
Ferrara, Italy
Novartis
Milano, Italy
Novartis
Padova, Italy
Spain
Novartis
Barcelona, Spain
Novartis
Madrid, Spain
Taiwan
Novartis
Taichung, Taiwan
United Kingdom
Novartis
Cambridge, United Kingdom
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: External Affairs, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00423098     History of Changes
Other Study ID Numbers: CERL080A2420
Study First Received: January 16, 2007
Results First Received: December 14, 2010
Last Updated: May 31, 2011
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Novartis:
Lupus Nephritis
enteric-coated mycophenolate sodium
EC-MPS
Myfortic

Additional relevant MeSH terms:
Lupus Nephritis
Nephritis
Glomerulonephritis
Kidney Diseases
Urologic Diseases
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisone
Prednisolone hemisuccinate
Prednisolone phosphate
Mycophenolic Acid
Mycophenolate mofetil
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Neuroprotective Agents
Protective Agents

ClinicalTrials.gov processed this record on July 26, 2014