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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Genentech
ClinicalTrials.gov Identifier:
NCT00282347
First received: January 24, 2006
Last updated: May 20, 2013
Last verified: May 2013
  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 3

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:


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
Study Completion Date: January 2013
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
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: NCT00282347

Sponsors and Collaborators
Genentech
Investigators
Study Director: Paul Brunetta, M.D Genentech
  More Information

No publications provided by Genentech

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Genentech
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: May 20, 2013
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 hemisuccinate
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

ClinicalTrials.gov processed this record on July 10, 2014