A Study to Evaluate the Efficacy and Safety of Rituximab in Subjects With ISN/RPS Class III or IV Lupus Nephritis (LUNAR) - Full Text View

Sponsor:	Genentech
Information provided by:	Genentech
ClinicalTrials.gov Identifier:	NCT00282347

Purpose

This is a Phase III, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of rituximab in combination with MMF compared with placebo in combination with mycophenolate mofetil (MMF) in subjects diagnosed with ISN/RPS 2003 Class III or IV Lupus Nephritis.

Condition	Intervention	Phase
Lupus Nephritis	Drug: corticosteroids Drug: methylprednisolone Drug: mycophenolate mofetil Drug: placebo Drug: rituximab	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Rituximab in Subjects With ISN/RPS Class III or IV Lupus Nephritis

Resource links provided by NLM:

Drug Information available for: Prednisolone Prednisolone acetate Depo-medrol Medrol veriderm Methylprednisolone Mycophenolate mofetil hydrochloride Mycophenolate Mofetil Rituximab Prednisolone sodium phosphate Prednisolone Sodium Succinate Methylprednisolone Sodium Succinate Methylprednisolone hemisuccinate 6-Methylprednisolone Corticosteroids

U.S. FDA Resources

Further study details as provided by Genentech:

Primary Outcome Measures:

Proportion of Subjects Who Achieve a Renal Response [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
Renal Response evaluated at 52 weeks, categorized in one of the three mutually exclusive categories: Complete renal response, Partial renal response, No clinically significant response.

Secondary Outcome Measures:

Change in C3 and C4 Complement Levels From Baseline [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
Change, from baseline to Week 52, in serum complement levels, C3 and C4.
Proportion of Subjects Who Achieve a Complete Renal Response [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
Achievement of a complete renal response at Week 52, defined by all of the following: normalization of serum creatinine, inactive urinary sediment and a urine protein to creatinine ratio <0.5.
Proportion of Subjects With a Baseline Urine Protein to Creatinine Ratio of > 3.0 Who Achieve a Urine Protein to Creatinine Ratio of < 1.0 [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
Achievement at Week 52 of a Urine Protein to Creatinine Ratio < 1, from a baseline ratio > 3.0 (nephritic range).
Time-adjusted Area Under the Concentration-time Curve Minus Baseline Area Under the Concentration-Time Curve Minus Baseline(AUCMB) of BILAG Global Score [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
A single alphabetic score (A through E) is used to denote disease severity for each of the 8 domains. The global BILAG score is the sum of a converted numerical score (A=9, B=3, C=1, D=0, E=0) over 8 domains. The AUCMB of BILAG Score Over 52 Weeks is calculated as:
1. Calculate the AUC of the BILAG global score versus time (in days) by 52 weeks.
2. Calculate the Time-Adjusted AUC by dividing the AUC by the number of days a patient was on the study.
3. Minus the Time-Adjusted AUC by the baseline BILAG global score
Time to Complete Renal Response [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
Number of weeks until achievement of the first complete renal response over 52 weeks.

The "number" in the outcome measure is equal to the 25th quantile.
Change in SLE Expanded Health Survey Physical Function Score [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
Short Form (36) with additional questions specific to lupus (scale = 0-100; with 100 representing the highest level of functioning possible) to measure the ability of rituximab to improve quality of life.
Change in Anti-double Stranded DNA From Baseline [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
Relative change in serum anti-dsDNA antibody levels calculated as the ratio between Week 52 level and baseline level.
Number of Subjects Who Achieved a Complete Renal Response at Week 24 and Maintained it to Week 52 [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
Achievement of a sustained complete renal response (at all visits from Week 24 to Week 52), defined by all of the following: normalization of serum creatinine, inactivity urinary sediment and a urine protein to creatinine ratio < 0.5.

Enrollment:	145
Study Start Date:	January 2006
Estimated Study Completion Date:	June 2011
Primary Completion Date:	January 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1	Drug: corticosteroids Intravenous or oral repeating dose Drug: methylprednisolone Intravenous repeating dose Drug: mycophenolate mofetil Intravenous repeating dose Drug: rituximab Intravenous repeating dose
Placebo Comparator: 2	Drug: corticosteroids Intravenous or oral repeating dose Drug: methylprednisolone Intravenous repeating dose Drug: mycophenolate mofetil Intravenous repeating dose Drug: placebo Intravenous repeating dose

Eligibility

Ages Eligible for Study:	16 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Diagnosis of SLE according to current ACR criteria
Diagnosis of ISN/RPS 2003 Class III or IV LN, with either active or active/chronic disease
Proteinuria
16-75 years of age

Exclusion Criteria:

Retinitis, poorly controlled seizure disorder, acute confusional state, myelitis, stroke or stroke syndrome, cerebellar ataxia, or dementia that is currently active and resulting from SLE
Unstable subjects with thrombocytopenia experiencing or at high risk for developing clinically significant bleeding or organ dysfunction requiring therapies such as plasmapheresis or acute blood or platelet transfusions
Lack of peripheral venous access
Pregnancy or lactation
History of severe allergic or anaphylactic reactions to monoclonal antibodies
Significant or uncontrolled medical disease in any organ system not related to SLE or LN, which, in the investigator's opinion, would preclude subject participation
Concomitant chronic conditions, excluding SLE (e.g., asthma, Crohn's disease) that require oral or systemic corticosteroid use in the 52 weeks prior to screening
History of renal transplant
Known HIV infection
Known active infection of any kind (but excluding fungal infection of nail beds) or any major episode of infection requiring hospitalization or treatment with intravenous anti-infectives within 4 weeks of randomization or oral anti-infectives within 2 weeks of randomization.
History of deep space infection within 1 year of screening
History of serious recurrent or chronic infection
History of cancer, including solid tumors, hematological malignancies and carcinoma in situ (except basal cell carcinomas of the skin that have been treated or excised and have resolved)
Currently active alcohol or drug abuse or history of alcohol or drug abuse within 52 weeks prior to screening
Major surgery requiring hospitalization within 4 weeks of screening (excluding diagnostic surgery)
Treatment with CYC or calcineurin inhibitors within the 90 days prior to screening
Use of MMF at a dose of > 2 grams daily for longer than the 90 days prior to screening
Intolerance or history of allergic reaction to MMF
Intolerance or history of allergic reaction to both angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers
Use of oral prednisone (or corticosteroid equivalent) at a dose of > 20 mg/day for longer than the 14 days prior to screening
Previous treatment with CAMPATH-1H
Previous treatment with a B-cell targeted therapy
Treatment with any investigational agent (including biologic agents approved for other indications) within 28 days of the start of the screening period or 5 half-lives of the investigational drug (whichever is longer)
Receipt of a live vaccine within the 28 days prior to screening
Intolerance or contraindication to oral or IV corticosteroids
Current therapy with a nonsteroidal anti-inflammatory agent
Positive hepatitis B sAg or hepatitis C serology

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00282347

Sponsors and Collaborators

Genentech

Investigators

Study Director:

Paul Brunetta, M.D

Genentech

More Information

No publications provided

Responsible Party:	Clinical Trials Posting Group, Genentech, Inc.
ClinicalTrials.gov Identifier:	NCT00282347 History of Changes
Other Study ID Numbers:	U2970g
Study First Received:	January 24, 2006
Results First Received:	February 1, 2010
Last Updated:	April 14, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Genentech:

Class IV LN
Lupus
LUNAR
LN

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
Prednisolone phosphate

Rituximab
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
Glucocorticoids

ClinicalTrials.gov processed this record on February 09, 2012