Etanercept for the Treatment of Lupus Nephritis - Full Text View

Sponsored by:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00447265

Purpose

Systemic lupus erythematosus (SLE) is a chronic, multisystem, autoimmune disease in which the body's immune system attacks its own normal tissues. This abnormal autoimmune response can result in damage to many parts of the body, including the skin, joints, lungs, heart, brain, intestines, and kidneys. Kidney problems occur in 60-75 % of lupus patients. The development of lupus-related kidney disease (called lupus nephritis) is associated with an overall worse prognosis.

SLE is usually treated with drugs that try to block inflammation caused by the immune system. These treatments can create their own problems and they do not cure lupus. The drugs that are often used to treat lupus nephritis include prednisone (steroids), cyclophosphamide (Cytoxan), azathioprine (AZA or Imuran), and mycophenolate mofetil (MMF or Cellcept). The main purpose of this study is to evaluate the safety and tolerability of etanercept compared to placebo in combination with standard of care to treat individuals with active lupus nephritis.

Condition	Intervention	Phase
Lupus Nephritis	Drug: Etanercept Drug: Lupus Treatment	Phase II

Drug Information available for: Etanercept Corticosteroids Mycophenolic acid Tumor Necrosis Factors

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver), Placebo Control, Parallel Assignment, Safety Study
Official Title:	A Randomized, Double-Blind, Placebo-Controlled, Phase II, Multi-Center Study for Treatment of Lupus Nephritis by Inhibition of Tumor Necrosis Factor-Alpha Using Etanercept

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Proportion of subjects in each study arm experiencing an adverse event of NCI CTCAE Grade 3 or greater [ Time Frame: At Week 24 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Safety analysis [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Efficacy analysis [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Renal response [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Time to and duration of renal response [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Changes over time [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Estimated Enrollment:	28
Study Start Date:	February 2008
Estimated Study Completion Date:	February 2009
Estimated Primary Completion Date:	February 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Participants in this group will self-administer 50 mg etanercept injections once a week for 24 weeks. They will continue receiving their usual treatment with corticosteroids and either MMF, Mycophenolic Acid, or AZA.	Drug: Etanercept TNF inhibitor that increased the number of reactive B and T cells Drug: Lupus Treatment Individualized standard of care treatment for lupus with corticosteroids and with MMF, Mycophenolic Acid, or AZA
2: Placebo Comparator Participants in this group will self-administer 50 mg placebo injections once a week for 24 weeks. They will continue receiving their usual treatment with corticosteroids and either MMF, Mycophenolic Acid, or AZA.	Drug: Lupus Treatment Individualized standard of care treatment for lupus with corticosteroids and with MMF, Mycophenolic Acid, or AZA

Detailed Description:

Kidney problems associated with lupus nephritis range from asymptomatic protein in the urine to rapidly progressive glomerulonephritis, leading to end-stage renal disease. The goal of therapies is to control kidney manifestations in order to avoid kidney failure, the occurrence of other medical problems and death.

The treatment of lupus nephritis remains problematic. Despite the use of currently available therapies, patients experience disease relapse. Over time, patients develop significant morbidity from the disease as well as from medications used for treatment.

Etanercept, a TNF inhibitor, is proposed as a potential treatment for lupus nephritis. TNF increases the number of reactive B and T cells. TNF levels can be elevated in lupus. Etanercept is believed to work by blocking inflammation, and it is hoped that it will lessen the signs and symptoms of lupus-related kidney disease.

The purpose of this study is to evaluate the safety and tolerability of etanercept compared to placebo in combination with standard therapy to treat individuals with mild or moderately active lupus nephritis.

This study will last 1 year. Participants will be randomly assigned to receive either etanercept or placebo in addition to their regular medications. Participants will self-administer 50 mg etanercept or placebo injections once a week. They will continue receiving their usual treatment with corticosteroids and either MMF, Mycophenolic Acid, or AZA. Treatment with study medication will occur for 24 weeks.

There will be a screening visit followed by a randomization visit, where subjects will receive and learn how to administer the study drug. Subjects will come to the clinic for 9 study visits. A physical exam and blood and urine collection will occur at most study visits. Participants will also be asked to complete a questionnaire on their health at most study visits. Subjects will be contacted by phone 5 times during the 24-week period to assess for adverse events and worsening disease status.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Meets at least 4 of the 11 American College of Rheumatology (ACR) 1982 Revised Criteria for the Classification of SLE
Active lupus nephritis
Currently has antibodies to double-stranded DNA (dsDNA)
Currently receiving treatment consisting of at least 1.5 g/day of MMF OR at least 720 mg/day orally of Mycophenolic Acid OR at least 1.5 mg/kg once per day of AZA for lupus nephritis, for at least 28 days prior to study entry
Stable medication regimen for at least 4 weeks prior to study entry
Able and willing to self-administer study drug OR has a designated caregiver at home to administer study drug injections
Willing to use acceptable forms of contraception for the duration of the study

Exclusion Criteria:

Moderately severe anemia
Neutropenia
Thrombocytopenia
Blood creatinine levels greater than 3.0 mg/dl
Positive PPD without ongoing treatment for at least 30 days prior to study entry
Pulmonary fibrotic changes
Active infections (e.g., HIV, hepatitis B virus [HBV], hepatitis C virus [HCV]) and/or serologic evidence of prior exposure to hepatitis B
Received a live vaccine within 3 months prior to study entry
Doubled serum creatinine levels within the 3 months prior to study entry OR end-stage kidney disease
Dialysis-dependent end-stage kidney disease or membranous nephritis
History of cancer. Individuals with a history of cervical carcinoma in situ and resected basal and squamous cell carcinomas of the skin are not excluded.
Receiving prednisone greater than 20 mg/day or equivalent corticosteroid treatment
Pulse intravenous methylprednisolone within 30 days prior to study entry
Receiving immunosuppressive agents other than prednisone, MMF, Mycophenolic Acid, AZA, or hydroxychloroquine
Oral or intravenous cyclosporine, leflunomide IVIG, or plasmapheresis within 3 months prior to study entry
Current or previous cyclophosphamide treatment
Use of other experimental agent within 90 days prior to study entry
Severe, progressive, or uncontrolled kidney, liver, blood, stomach, lung, heart, or brain disease. Individuals with any of these conditions that are related to active SLE are not excluded.
Previous use of rituximab within 12 months prior to study entry
Previous or current exposure to any of the following: etanercept (Enbrel), adalimumab (Humira), infliximab (Remicade), or anakinra (Kineret)
Meets New York Heart Association classification of congestive heart failure (CHF) Class III or greater
History of myocardial infarction or ischemia
Current or history of substance abuse
Known hypersensitivity to any component of the study drug
Poorly controlled or advanced diabetes mellitus
History of multiple sclerosis, transverse myelitis, optic neuritis, or epilepsy
History of noncompliance with other therapies
Pregnancy or breastfeeding

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00447265

Locations

United States, Alabama
University of Alabama at Birmingham	Not yet recruiting
Birmingham, Alabama, United States, 35294
Contact: Linda Cowden, RN 205-934-2991 Linda.Cowden@ccc.uab.edu
Principal Investigator: Winn Chatham, MD
United States, California
University of California at San Francisco	Recruiting
San Francisco, California, United States, 94143
Contact: Steve Lund, NP 415-502-1886 Steve.lund@ucsf.edu
Principal Investigator: Maria Dall'Era, MD
United States, Colorado
University of Colorado Health Sciences Center	Recruiting
Aurora, Colorado, United States, 80045
Contact: Janice Wagner, RN, CCRC 303-724-7516 Janice.Wagner@uchsc.edu
Principal Investigator: Christopher Striebich, MD, PhD
United States, New York
Feinstein Institute for Medical Research NS-L1J Health System	Recruiting
Manhasset, New York, United States, 11030
Contact: Sanita Kandasami 516-562-2401 SKandasami@nshs.edu
Principal Investigator: Cynthia Aranow, MD
University of Rochester	Not yet recruiting
Rochester, New York, United States, 14642
Contact: Emily Cushing 585-275-7167 Emily_Cushing@urmc.rochester.edu
Principal Investigator: John Looney, MD
United States, North Carolina
Duke University Medical Center	Recruiting
Durham, North Carolina, United States, 27709
Contact: Martin Tochacek 919-684-5586 martin.tochacek@duke.edu
Principal Investigator: Lisa Criscione-Schreiber, MD

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair:	Maria Dall'Era, MD	Division of Rheumatology, University of California, San Francisco
Study Chair:	David Wofsy, MD	Department of Medicine, University of California, San Francisco

More Information

Publications:

Aringer M, Graninger WB, Steiner G, Smolen JS. Safety and efficacy of tumor necrosis factor alpha blockade in systemic lupus erythematosus: an open-label study. Arthritis Rheum. 2004 Oct;50(10):3161-9.

De Rycke L, Baeten D, Kruithof E, Van den Bosch F, Veys EM, De Keyser F. The effect of TNFalpha blockade on the antinuclear antibody profile in patients with chronic arthritis: biological and clinical implications. Lupus. 2005;14(12):931-7. Review.

Mor A, Bingham C 3rd, Barisoni L, Lydon E, Belmont HM. Proliferative lupus nephritis and leukocytoclastic vasculitis during treatment with etanercept. J Rheumatol. 2005 Apr;32(4):740-3.

Scheinfeld N. A comprehensive review and evaluation of the side effects of the tumor necrosis factor alpha blockers etanercept, infliximab and adalimumab. J Dermatolog Treat. 2004 Sep;15(5):280-94. Review.

Responsible Party:	DAIT/NIAID ( Associate Director, Clinical Research Program )
Study ID Numbers:	DAIT ALN01
Study First Received:	March 12, 2007
Last Updated:	December 18, 2008
ClinicalTrials.gov Identifier:	NCT00447265
Health Authority:	United States: Food and Drug Administration

Study placed in the following topic categories:

Glomerulonephritis
Necrosis
Autoimmune Diseases
Lupus Erythematosus, Systemic
Urologic Diseases
Lupus Nephritis

Nephritis
Mycophenolic Acid
Connective Tissue Diseases
Kidney Diseases
TNFR-Fc fusion protein

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Immunologic Factors
Immune System Diseases
Physiological Effects of Drugs
Gastrointestinal Agents
Immunosuppressive Agents
Pharmacologic Actions
Analgesics, Non-Narcotic

Sensory System Agents
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Peripheral Nervous System Agents
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 16, 2009