Etanercept for the Treatment of Lupus Nephritis

NCT00447265 | Terminated Phase 2 Results

• 1 other identifier: DAIT ALN01
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Lupus Nephritis

Outcome Measures

Primary Outcomes (1)

• Number of Adverse Events (AEs)Grade 3 or Higher Experienced by Participant During Treatment Phase of Study

  Number of adverse events (AEs) or serious adverse events (SAEs) Grade 3 or higher experienced by participant over the duration of the treatment period. \[1\] \[1\] This study graded the severity of AEs experienced by the study participant according to the criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0.

  24 Weeks

Secondary Outcomes (9)

• Number of Participant Adverse Events (AEs) From Baseline to Early Study Withdrawal Visit

  39 Weeks

• Percent of Participants Who Achieved a Renal Response at Week 24

  Week 24

• Time to Participant's Renal Response

  First 24 Weeks of Study Period

• Participant Systematic Lupus Erythematosus Disease Activity Index (SLEDAI) Score at Baseline and at Early Study Withdrawal Visit

  Baseline, Week 39 (Early Study Withdrawal Visit)

• Number of Participants With a C to B Score Change From Baseline to Week 24 in the British Isles Lupus Assessment Group (BILAG) Mucocutaneous Score

  Baseline, Week 24

Study Arms (2)

Etanercept

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 mycophenolate mofetil (MMF), mycophenolic acid, or azathioprine (AZA).

Drug: Etanercept; Drug: Lupus Treatment- Standard of Care

Placebo

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 mycophenolate mofetil (MMF), mycophenolic acid, or azathioprine (AZA).

Drug: Lupus Treatment- Standard of Care; Drug: Placebo

Interventions

Etanercept DRUG

1.) Immune suppressant. 2.) Tumor necrosis factor (TNF) inhibitor.

Also known as: Enbrel

Etanercept

Lupus Treatment- Standard of Care DRUG

Individualized standard of care treatment for lupus with corticosteroids and with mycophenolate mofetil (MMF), mycophenolic acid, or azathioprine (AZA)

Etanercept; Placebo

Placebo DRUG

Placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (6)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

University of California at San Francisco

San Francisco, California, 94143, United States

Location

University of Colorado Health Sciences Center

Aurora, Colorado, 80045, United States

Location

Feinstein Institute for Medical Research NS-L1J Health System

Manhasset, New York, 11030, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Duke University Medical Center

Durham, North Carolina, 27709, United States

Location

Related Publications (4)

• 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. doi: 10.1002/art.20576.

  PMID: 15476222 BACKGROUND

• 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. doi: 10.1191/0961203305lu2240rr.

  PMID: 16425572 BACKGROUND

• Mor A, Bingham CO 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.

  PMID: 15801034 BACKGROUND

• 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. doi: 10.1080/09546630410017275.

  PMID: 15370396 BACKGROUND

MeSH Terms

Conditions

Lupus Nephritis

Interventions

Etanercept

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)

Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulin Constant Regions; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins

Limitations and Caveats

The study terminated early with 1 subject enrolled. Based on safety info from other trials, the protocol chairs decided possible risks to patients outweighed the potential benefits. Analysis of groups is not possible. Study objectives cannot be met.

Results Point of Contact

• Title: Associate Director for Clinical Research
• Organization: DAIT/NIAID

DAITClinicalTrialsGov@niaid.nih.gov

301-594-7669

Study Officials

• 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

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2007
• First Posted: March 14, 2007
• Study Start: February 1, 2008
• Primary Completion: March 1, 2009
• Study Completion: March 1, 2009
• Last Updated: February 12, 2013
• Results First Posted: December 19, 2011

Record last verified: 2013-02

Locations

US (6)