Nelfinavir in Systemic Lupus Erythematosus

Study Overview
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Brief Summary
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Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease in which the body's immune system attacks different parts of the body. SLE is characterized by inflammation that leads to tissue damage in different organ systems. Any organ system may be involved, including the skin, the joints, the kidneys, the nervous system, the heart, the lungs, and the blood. The exact cause of SLE is not known. Patients with SLE often have elevated levels of anti-double stranded DNA antibodies. These levels are often associated with disease flares and disease severity. These antibodies can bind to tissue leading to organ damage. Preventing these antibodies from binding to their targets may help decrease disease activity. Protease inhibitors are medications that have been approved by the Food and Drug Administration (FDA) for use in the treatment of HIV (human immunodeficiency virus). Nelfinavir (also called viracept) is one of these protease inhibitors. Separate from their anti-viral effects, protease inhibitors have been found to decrease inflammation. These medications have been shown to interfere with binding of anti-double stranded DNA antibodies to their targets and may decrease inflammation in SLE. This research study tests whether the protease inhibitor, nelfinavir, will decrease anti-double stranded DNA antibody binding and decrease disease activity.

Official Title
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Nelfinavir in Systemic Lupus Erythematosus: A Pilot Phase IIa Clinical Trial

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: Nelfinavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is capable of providing written informed consent Subject is ≥ 18 years old and ≤ 65 years old Meets at least 4 of 11 modified American College of Rheumatology (ACR) (1997) Revised Criteria for the Classification of Systemic Lupus Erythematosus Has mild to moderate disease activity defined as A minimum SLEDAI score of 2 excluding points for serology (anti-dsDNA antibody and complement) No active renal or nervous system disease No BILAG A in any organ system No expectation by the investigator that corticosteroids will need to be added or doses increased during the 8 week treatment period for any reason No expectation by the investigator that immunosuppressive medication will need to be added or doses increased during the 8 week treatment period Has elevated titers of anti-ds DNA antibody at the time of screening (defined as the titer that meets criteria for high in the Core Laboratory at the North Shore/LIJ Health Systems; unequivocal high titer as opposed to borderline, indeterminate or intermediate). Has elevated titers of cross-reactive anti-DNA/DWEYS antibodies at the time of screening (the assays for anti-DNA/DWEYS antibodies will be performed in Dr. B. Diamond's laboratory; study sites will be notified of results within 3 days of receipt of the samples). If on glucocorticoids, the dose must be ≤10 mg daily and stable for the 4 weeks prior to screening and baseline If on immunosuppressive or immunomodulatory medication such as azathioprine, methotrexate, leflunomide, mycophenolate, or hydroxychloroquine, the dose must have been stable for the 3 months prior to screening, and expected to remain stable over the course of the study. Males and females with potential for reproduction must agree to practice effective birth control measures (2 approved methods of contraception). Nelfinavir can decrease serum levels of oral contraceptives; the slightly increased risk of pregnancy due to an interaction between oral contraception and nelfinavir will be discussed when appropriate and the requirement for a second approved method of contraception will be addressed. Exclusion Criteria: Current or prior treatment with rituximab, belimumab or anti-CD22 monoclonal antibody in the 12 months prior to this study or any other biologic agent for 90 days prior to this study Treatment with cyclophosphamide within the 6 months prior to screening Increase in glucocorticoid dose within 4 weeks of screening or addition of a DMARD in the three months prior to study A history of drug or alcohol abuse within the 6 months prior to screening Elevated LFT's: ALT or AST ≥ 2 x upper limit of normal at screening serum unconjugated bilirubin > 3mg/dL at screening Dialysis or serum creatinine >1.5mg/dL Hypercholesterolemia: total cholesterol >230 mg/dL or LDL >150 mg/dl or hypertriglyceridemia (triglyceride >200mg/dL) at screening Laboratory/clinical evidence of: pancreatitis: amylase/lipase >3x upper limit of normal at screening Known current/active infections including HIV, Hepatitis B, Hepatitis C History of cancer, excluding skin cancers (squamous cell or basal cell that have been treated) Known active tuberculosis or untreated tuberculosis Hemoglobin < 8 g/dL Expectation by the investigator to increase corticosteroid or immunosuppressive, or immunomodulatory medication dose at screening, baseline, or over the course of the study Pregnancy or lactation Consumption of > 2 cups of grapefruit juice per day Treatment with medications metabolized using the cytochrome P3A4 pathway, such as cyclosporine, tacrolimus, gemfibrozil, niacin, itraconazole, ketoconazole, erythromycin, azithromycin, clarithromycin, bosentan, nefazodone, tricyclic antidepressants Any condition that, in the opinion of the Investigator, would jeopardize the subject's safety following exposure to the study drug.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: nelfinavir<br>Nelfinavir tablets will be taken by oral administration, 750mg (three 250 mg tablets) three times a day | Drug: Nelfinavir<br> <br> * Other names: Viracept;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inhibition of Anti-dsDNA Binding | Change in serum anti-dsDNA titer from baseline to Day 56; a decrease in titer ≥ 35% was considered a positive response | baseline to Day 56 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lupus, SLE