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

NCT00423098 | Completed Phase 2 Results

• 1 other identifier: CERL080A2420
• Study Type: interventional
• Target: 81
• Locations: 9 countries
• Sites: 17

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)

Conditions

Lupus Nephritis

Keywords

Lupus Nephritis; enteric-coated mycophenolate sodium; EC-MPS; Myfortic

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (9)

• Number of Patients With Complete Remission

  12 Weeks

• Number of Patients With Partial Remission

  Baseline to 12 and 24 weeks

• Cumulative Dose of Prednisone Equivalent Corticosteroids (CS)

  12 Weeks and 24 Weeks

• Number of Patients With Moderate to Severe Flares

  12 and 24 weeks

• Duration of Exposure to Study Medication

  24 weeks

Study Arms (2)

Standard dose

EXPERIMENTAL

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; Drug: Prednisone; Drug: Methylprednisolone

Low dose

ACTIVE COMPARATOR

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; Drug: Prednisone; Drug: Methylprednisolone

Interventions

Mycophenolate sodium DRUG

Mycophenolate sodium as administered orally for 2 weeks at 1440mg daily and then increased to 2160mg daily for 22 weeks.

Also known as: Myfortic

Low dose; Standard dose

Prednisone DRUG

Oral prednisone or prednisone equivalent was started on Day 4 and subsequently tapered every 2 weeks according to the patient's weight.

Low dose; Standard dose

Methylprednisolone DRUG

All patients received bolus therapy with 0.5 g of intravenous Methylprednisolone per day for 3 consecutive days.

Low dose; Standard dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (17)

Novartis

Bogotá, Colombia

Location

Novartis

Créteil, France

Location

Novartis

Nantes, France

Location

Novartis Investigative Site

Paris, France

Location

Novartis

Berlin, Germany

Location

Novartis

Tübingen, Germany

Location

Novartis

Athens, Greece

Location

Novartis

Budapest, Hungary

Location

Novartis

Debrecen, Hungary

Location

Novartis

Brescia, Italy

Location

Novartis

Ferrara, Italy

Location

Novartis

Milan, Italy

Location

Novartis

Padua, Italy

Location

Novartis

Barcelona, Spain

Location

Novartis

Madrid, Spain

Location

Novartis

Taichung, Taiwan

Location

Novartis

Cambridge, United Kingdom

Location

MeSH Terms

Conditions

Lupus Nephritis

Interventions

Mycophenolic Acid; Prednisone; Methylprednisolone

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lupus Erythematosus, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Prednisolone; Pregnadienetriols

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: January 16, 2007
• First Posted: January 17, 2007
• Study Start: February 1, 2007
• Primary Completion: November 1, 2009
• Study Completion: November 1, 2009
• Last Updated: June 28, 2011
• Results First Posted: June 28, 2011

Record last verified: 2011-05

Locations

ES (2); DE (2); TW (1); GR (1); GB (1); IT (4); CO (1); FR (3); HU (2)