A Study to Evaluate the Efficacy and Safety of Rituximab in Subjects With International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 Class III or IV Lupus Nephritis (LUNAR)

January 6, 2015 updated by: Genentech, Inc.

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

This was a Phase III, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of rituximab in combination with mycophenolate mofetil (MMF) compared with placebo in combination with MMF in subjects diagnosed with International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 Class III or IV lupus nephritis.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

In addition to receiving study drug (rituximab or placebo), participants in each treatment group received mycophenolate mofetil at a starting dose of 1500 mg/day IV in 3 divided doses and were titrated up by 500 mg/week to 3000 mg/day by Week 4, as tolerated. Participants in each treatment group also received methylprednisolone 1000 mg IV prior to and 3 days following the first study drug infusion and methylprednisolone 100 mg IV prior to the other study drug infusions. Participants in each treatment group also received diphenhydramine 50 mg orally and acetaminophen 1000 mg orally 30-60 minutes prior to each study drug infusion. From Days 2 to 16, participants in each treatment group received prednisone 0.75 mg/kg/day orally (maximum dose of 60 mg) except on the day of the second methylprednisolone dose. On Day 16, a taper was initiated to achieve a dose of 10 mg/day by Week 16.

Study Type

Interventional

Enrollment (Actual)

144

Phase

  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 75 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Diagnosis of systemic lupus erythematosus (SLE) according to current American College of Rheumatology (ACR) criteria.
  • Diagnosis of International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 Class III or IV lupus nephritis (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 (eg, asthma, Crohn's disease) that require oral or systemic corticosteroid use in the 52 weeks prior to screening.
  • History of renal transplant.
  • Known human immunodeficiency virus (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 cyclophosphamide or calcineurin inhibitors within the 90 days prior to screening.
  • Use of mycophenolate mofetil (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 (alemtuzumab).
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Rituximab
Participants received rituximab 1000 mg intravenously (IV) on Days 1, 15, 168, and 182. They also received mycophenolate mofetil, methylprednisolone, diphenhydramine, acetaminophen, and prednisone; see the Detailed Description for details.
Drug: Prednisone
Drug: Mycophenolate mofetil
Other Names:
  • CellCept
Drug: Methylprednisolone
Drug: Acetaminophen
Drug: Diphenhydramine
Drug: Rituximab
Rituximab was provided as a sterile solution for injection.
Other Names:
  • Rituxan
  • MabThera
  • Zytux
Placebo Comparator: Placebo
Participants received placebo intravenously (IV) on Days 1, 15, 168, and 182. They also received mycophenolate mofetil, methylprednisolone, diphenhydramine, acetaminophen, and prednisone; see the Detailed Description for details.
Drug: Prednisone
Drug: Mycophenolate mofetil
Other Names:
  • CellCept
Drug: Methylprednisolone
Drug: Acetaminophen
Drug: Diphenhydramine
Drug: Placebo
Placebo was provided as a sterile solution for injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants Who Achieved a Complete Renal Response (CRR), a Partial Renal Response (PRR), or no Renal Response (NRR) at Week 52
Time Frame: Week 52
A participant had a CRR if they met the following 3 criteria: (1) Normalization of serum creatinine (SC) as evidenced by a SC level ≤ the upper limit of the normal range of central laboratory values or a SC level ≤ 15% greater than Baseline, if Baseline SC was within the normal range of the central laboratory values; (2) Inactive urinary sediment (as evidenced by < 5 red blood cells/high-power field (RBCs/HPF) and absence of red cell casts; (3) Urinary protein (UP) to creatinine ratio (CR) < 0.5. A participant had a PRR if they met the following 3 criteria: (1) A SC level ≤ 15% above Baseline; (2) RBCs/HPF ≤ 50% above Baseline and no RBC casts; (3) 50% improvement in the UP to CR, with 1 of the following conditions met: If the Baseline UP to CR was ≤ 3.0, then a UP to CR of < 1.0 or if the Baseline UP to CR was > 3.0, then a UP to CR of ≤ 3.0. A participant had a NRR if they did not achieve either a CRR or PRR.
Week 52

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants Who Achieved a Complete Renal Response at Week 24 and Maintained it to Week 52
Time Frame: Week 24 to Week 52
A participant had a complete renal response if they met the following 3 criteria: (1) Normalization of serum creatinine as evidenced by a serum creatinine level ≤ the upper limit of the normal range of central laboratory values or a serum creatinine level ≤ 15% greater than Baseline, if Baseline serum creatinine was within the normal range of the central laboratory values; (2) Inactive urinary sediment (as evidenced by < 5 red blood cells/high-power field and absence of red cell casts; (3) Urinary protein to creatinine ratio < 0.5.
Week 24 to Week 52
Percentage of Participants Who Achieved a Complete Renal Response at Week 52
Time Frame: Week 52
A participant had a complete renal response if they met the following 3 criteria: (1) Normalization of serum creatinine as evidenced by a serum creatinine level ≤ the upper limit of the normal range of central laboratory values or a serum creatinine level ≤ 15% greater than Baseline, if Baseline serum creatinine was within the normal range of the central laboratory values; (2) Inactive urinary sediment (as evidenced by < 5 red blood cells/high-power field and absence of red cell casts; (3) Urinary protein to creatinine ratio < 0.5.
Week 52
Percentage of Participants With a Baseline Urine Protein to Creatinine Ratio of > 3.0 Who Achieved a Urine Protein to Creatinine Ratio of < 1.0 at Week 52
Time Frame: Baseline to Week 52
Baseline to Week 52
British Isles Lupus Assessment Group (BILAG) Index Score Over 52 Weeks
Time Frame: Baseline to Week 52
The BILAG Index assesses 86 clinical signs and symptoms and laboratory measures of systemic lupus erythematosus in 8 organ system domains: General, mucocutaneous, neurological, musculoskeletal, cardiorespiratory, vasculitis, renal, and hematologic. Most of the 86 items are rated on the following scale: 0=Not present, 1=Improving, 2=Same, 3=Worse, 4=New. Some items are rated as either Yes or No. A single alphabetic score of A (very active) through E (not or never active) for each of the 8 domains is determined from the rating of the individual items in each domain. The total BILAG score is the sum of the scores of the 8 domains where A=9, B=3, C=1, D=0, and E=0. The total score ranges from 0 to 72 with a higher score indicating greater lupus activity. To calculate a BILAG score over the 52 week treatment period of the study, the area under the response-time curve of BILAG scores assessed every 4 weeks was divided by the number of days in the time curve minus the Baseline BILAG score.
Baseline to Week 52
Time to Achieve a Complete Renal Response
Time Frame: Baseline to Week 52
Baseline to Week 52
Change From Baseline in the Systemic Lupus Erythematosus Expanded Health Survey Physical Function Score at Week 52
Time Frame: Baseline to Week 52
The systemic lupus erythematosus Expanded Health Survey is based on the Short Form 36 Health survey with additional questions specific to lupus. The physical function component score of the survey can range from 0-100. A higher score indicates better health. A positive change score indicates improvement.
Baseline to Week 52
Change From Baseline in Anti-double-stranded DNA at Week 52
Time Frame: Baseline to Week 52
Baseline to Week 52
Change From Baseline in C3 and C4 Complement Levels at Week 52
Time Frame: Baseline to Week 52
Baseline to Week 52

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Genentech, Inc.

Investigators

  • Study Director: Paul Brunetta, MD, Genentech, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2006

Primary Completion (Actual)

January 1, 2009

Study Completion (Actual)

January 1, 2013

Study Registration Dates

First Submitted

January 24, 2006

First Submitted That Met QC Criteria

January 24, 2006

First Posted (Estimate)

January 26, 2006

Study Record Updates

Last Update Posted (Estimate)

January 15, 2015

Last Update Submitted That Met QC Criteria

January 6, 2015

Last Verified

January 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • U2970g

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Lupus Nephritis

Clinical Trials on Prednisone

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Argentina

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe