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

Lupus Nephritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00423098
• Other study ID #: CERL080A2420
• Status: Completed
• Phase: Phase 2
• First received: January 16, 2007
• Last updated: May 31, 2011
• Start date: February 2007
• Est. completion date: November 2009

Study information

• Verified date: May 2011
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 81
• Est. completion date: November 2009
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lupus Nephritis
• Nephritis

Intervention

Drug:
• Mycophenolate sodium
Mycophenolate sodium as administered orally for 2 weeks at 1440mg daily and then increased to 2160mg daily for 22 weeks.
• Prednisone
Oral prednisone or prednisone equivalent was started on Day 4 and subsequently tapered every 2 weeks according to the patient's weight.
• Methylprednisolone
All patients received bolus therapy with 0.5 g of intravenous Methylprednisolone per day for 3 consecutive days.

Locations

Country	Name	City	State
Colombia	Novartis	Bogota
France	Novartis	Creteil
France	Novartis	Nantes
France	Novartis Investigative Site	Paris
Germany	Novartis	Berlin
Germany	Novartis	Tubingen
Greece	Novartis	Athens
Hungary	Novartis	Budapest
Hungary	Novartis	Debrecen
Italy	Novartis	Brescia
Italy	Novartis	Ferrara
Italy	Novartis	Milano
Italy	Novartis	Padova
Spain	Novartis	Barcelona
Spain	Novartis	Madrid
Taiwan	Novartis	Taichung
United Kingdom	Novartis	Cambridge

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Colombia,  France,  Germany,  Greece,  Hungary,  Italy,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	24 Weeks	No
Secondary	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.	12 Weeks	No
Secondary	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.	Baseline to 12 and 24 weeks	No
Secondary	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.	12 Weeks and 24 Weeks	No
Secondary	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)	12 and 24 weeks	No
Secondary	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.	24 weeks	No
Secondary	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.	24 weeks	No
Secondary	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.	12 Weeks and 24 Weeks	Yes
Secondary	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.	From Baseline to week 4, week 12 and week 24	No
Secondary	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].	From Baseline to week 4, week 12 and week 24	No