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
Overview
- Phase
- Phase 2
- Intervention
- Etanercept
- Conditions
- Lupus Nephritis
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 1
- Locations
- 6
- Primary Endpoint
- Number of Adverse Events (AEs)Grade 3 or Higher Experienced by Participant During Treatment Phase of Study
- Status
- Terminated
- Last Updated
- 13 years ago
Overview
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.
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.
Investigators
Eligibility 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
Arms & Interventions
Etanercept
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).
Intervention: Etanercept
Etanercept
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).
Intervention: Lupus Treatment- Standard of Care
Placebo
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).
Intervention: Lupus Treatment- Standard of Care
Placebo
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).
Intervention: Placebo
Outcomes
Primary Outcomes
Number of Adverse Events (AEs)Grade 3 or Higher Experienced by Participant During Treatment Phase of Study
Time Frame: 24 Weeks
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.
Secondary Outcomes
- 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)
- Number of Participants With a B to D Change From Baseline to Week 24 in the British Isles Lupus Assessment Group (BILAG) Musculoskeletal Score(Baseline, Week 24)
- Number of Participants With an A to B Score Change From Baseline to Week 24 in the British Isles Lupus Assessment Group (BILAG) Renal Score(Baseline, Week 24)
- Participant Medical Outcome Study Short-Form 36 (SF-36) Physical Component Score at Baseline and Week 24(Baseline, Week 24)
- Participant Medical Outcome Study Short Form 36 (SF-36) Mental Component Score at Baseline and Week 24(Baseline, Week 24)