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

Primary Purpose

Lupus Nephritis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Mycophenolate sodium
Prednisone
Methylprednisolone
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lupus Nephritis focused on measuring Lupus Nephritis, enteric-coated mycophenolate sodium, EC-MPS, Myfortic

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Novartis
  • Novartis
  • Novartis
  • Novartis Investigative Site
  • Novartis
  • Novartis
  • Novartis
  • Novartis
  • Novartis
  • Novartis
  • Novartis
  • Novartis
  • Novartis
  • Novartis
  • Novartis
  • Novartis
  • Novartis

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Standard dose

Low dose

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Number of Patients With Complete Remission
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
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
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)
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
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
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
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
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)
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)
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].

Full Information

First Posted
January 16, 2007
Last Updated
May 31, 2011
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00423098
Brief Title
Efficacy and Safety of Enteric-coated Mycophenolate Sodium in Combination With Two Corticosteroid Regimens for the Treatment of Lupus Nephritis Flare
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2011
Overall Recruitment Status
Completed
Study Start Date
February 2007 (undefined)
Primary Completion Date
November 2009 (Actual)
Study Completion Date
November 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

5. Study Description

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lupus Nephritis
Keywords
Lupus Nephritis, enteric-coated mycophenolate sodium, EC-MPS, Myfortic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
81 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Standard dose
Arm Type
Experimental
Arm Description
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.
Arm Title
Low dose
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Mycophenolate sodium
Other Intervention Name(s)
Myfortic
Intervention Description
Mycophenolate sodium as administered orally for 2 weeks at 1440mg daily and then increased to 2160mg daily for 22 weeks.
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
Oral prednisone or prednisone equivalent was started on Day 4 and subsequently tapered every 2 weeks according to the patient's weight.
Intervention Type
Drug
Intervention Name(s)
Methylprednisolone
Intervention Description
All patients received bolus therapy with 0.5 g of intravenous Methylprednisolone per day for 3 consecutive days.
Primary Outcome Measure Information:
Title
Number of Patients With Complete Remission
Description
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.
Time Frame
24 Weeks
Secondary Outcome Measure Information:
Title
Number of Patients With Complete Remission
Description
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.
Time Frame
12 Weeks
Title
Number of Patients With Partial Remission
Description
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.
Time Frame
Baseline to 12 and 24 weeks
Title
Cumulative Dose of Prednisone Equivalent Corticosteroids (CS)
Description
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.
Time Frame
12 Weeks and 24 Weeks
Title
Number of Patients With Moderate to Severe Flares
Description
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)
Time Frame
12 and 24 weeks
Title
Duration of Exposure to Study Medication
Description
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.
Time Frame
24 weeks
Title
Number of Patients With Adverse Events and Infections
Description
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.
Time Frame
24 weeks
Title
Number of Patients With Treatment Failure
Description
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.
Time Frame
12 Weeks and 24 Weeks
Title
Change From Baseline in Overall Disease Activity With Systematic Lupus Erythematosus Disease Activity Index (SLEDAI)
Description
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.
Time Frame
From Baseline to week 4, week 12 and week 24
Title
Change From Baseline in Overall Disease Activity With British Isles Lupus Assessment Group (BILAG)
Description
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].
Time Frame
From Baseline to week 4, week 12 and week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis
City
Bogota
Country
Colombia
Facility Name
Novartis
City
Creteil
Country
France
Facility Name
Novartis
City
Nantes
Country
France
Facility Name
Novartis Investigative Site
City
Paris
Country
France
Facility Name
Novartis
City
Berlin
Country
Germany
Facility Name
Novartis
City
Tubingen
Country
Germany
Facility Name
Novartis
City
Athens
Country
Greece
Facility Name
Novartis
City
Budapest
Country
Hungary
Facility Name
Novartis
City
Debrecen
Country
Hungary
Facility Name
Novartis
City
Brescia
Country
Italy
Facility Name
Novartis
City
Ferrara
Country
Italy
Facility Name
Novartis
City
Milano
Country
Italy
Facility Name
Novartis
City
Padova
Country
Italy
Facility Name
Novartis
City
Barcelona
Country
Spain
Facility Name
Novartis
City
Madrid
Country
Spain
Facility Name
Novartis
City
Taichung
Country
Taiwan
Facility Name
Novartis
City
Cambridge
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

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

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