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

NCT00282347 | Completed Phase 3 Results

• 1 other identifier: U2970g
• Study Type: interventional
• Target: 144
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Lupus Nephritis

Keywords

Class IV LN; Lupus; LUNAR; LN

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Achieved a Complete Renal Response (CRR), a Partial Renal Response (PRR), or no Renal Response (NRR) at 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 Outcomes (8)

• Percentage of Participants Who Achieved a Complete Renal Response at Week 24 and Maintained it to Week 52

  Week 24 to Week 52

• Percentage of Participants Who Achieved a Complete Renal Response at Week 52

  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

  Baseline to Week 52

• British Isles Lupus Assessment Group (BILAG) Index Score Over 52 Weeks

  Baseline to Week 52

• Time to Achieve a Complete Renal Response

  Baseline to Week 52

Study Arms (2)

Rituximab

EXPERIMENTAL

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: Rituximab; Drug: Mycophenolate mofetil; Drug: Methylprednisolone; Drug: Diphenhydramine; Drug: Acetaminophen; Drug: Prednisone

Placebo

PLACEBO COMPARATOR

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: Placebo; Drug: Mycophenolate mofetil; Drug: Methylprednisolone; Drug: Diphenhydramine; Drug: Acetaminophen; Drug: Prednisone

Interventions

Rituximab DRUG

Rituximab was provided as a sterile solution for injection.

Also known as: Rituxan, MabThera, Zytux

Rituximab

Placebo DRUG

Placebo was provided as a sterile solution for injection.

Placebo

Mycophenolate mofetil DRUG

Also known as: CellCept

Placebo; Rituximab

Methylprednisolone DRUG

Placebo; Rituximab

Diphenhydramine DRUG

Placebo; Rituximab

Acetaminophen DRUG

Placebo; Rituximab

Prednisone DRUG

Placebo; Rituximab

Eligibility Criteria

• Age: 16 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• years of age.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Genentech, Inc.: lead

Related Publications (3)

• Gomez Mendez LM, Cascino MD, Garg J, Katsumoto TR, Brakeman P, Dall'Era M, Looney RJ, Rovin B, Dragone L, Brunetta P. Peripheral Blood B Cell Depletion after Rituximab and Complete Response in Lupus Nephritis. Clin J Am Soc Nephrol. 2018 Oct 8;13(10):1502-1509. doi: 10.2215/CJN.01070118. Epub 2018 Aug 8.

  PMID: 30089664 DERIVED

• Wolf BJ, Spainhour JC, Arthur JM, Janech MG, Petri M, Oates JC. Development of Biomarker Models to Predict Outcomes in Lupus Nephritis. Arthritis Rheumatol. 2016 Aug;68(8):1955-63. doi: 10.1002/art.39623.

  PMID: 26867033 DERIVED

• Rovin BH, Furie R, Latinis K, Looney RJ, Fervenza FC, Sanchez-Guerrero J, Maciuca R, Zhang D, Garg JP, Brunetta P, Appel G; LUNAR Investigator Group. Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the Lupus Nephritis Assessment with Rituximab study. Arthritis Rheum. 2012 Apr;64(4):1215-26. doi: 10.1002/art.34359. Epub 2012 Jan 9.

  PMID: 22231479 DERIVED

MeSH Terms

Conditions

Lupus Nephritis

Interventions

Rituximab; Mycophenolic Acid; Methylprednisolone; Diphenhydramine; Acetaminophen; Prednisone

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)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Ethylamines; Amines; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Acetanilides; Anilides; Amides; Aniline Compounds; Pregnadienediols

Results Point of Contact

• Title: Medical Communications
• Organization: Genentech, Inc.

800-821-8590

Study Officials

• Paul Brunetta, MD

  Genentech, Inc.

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2006
• First Posted: January 26, 2006
• Study Start: January 1, 2006
• Primary Completion: January 1, 2009
• Study Completion: January 1, 2013
• Last Updated: January 15, 2015
• Results First Posted: February 23, 2010

Record last verified: 2015-01