Nelfinavir in Systemic Lupus Erythematosus (NISLE)

This is an interventional treatment trial for Systemic Lupus Erythematosus focused on measuring lupus, SLE Read More

Inclusion Criteria:

1. Subject is capable of providing written informed consent
2. Subject is ≥ 18 years old and ≤ 65 years old
3. Meets at least 4 of 11 modified American College of Rheumatology (ACR) (1997) Revised Criteria for the Classification of Systemic Lupus Erythematosus

4. 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
5. 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).
6. 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).
7. If on glucocorticoids, the dose must be ≤10 mg daily and stable for the 4 weeks prior to screening and baseline
8. 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.
9. 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:

1. 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
2. Treatment with cyclophosphamide within the 6 months prior to screening
3. Increase in glucocorticoid dose within 4 weeks of screening or addition of a DMARD in the three months prior to study
4. A history of drug or alcohol abuse within the 6 months prior to screening

5. Elevated LFT's:

   • ALT or AST ≥ 2 x upper limit of normal at screening
   • serum unconjugated bilirubin > 3mg/dL at screening
6. Dialysis or serum creatinine >1.5mg/dL
7. Hypercholesterolemia: total cholesterol >230 mg/dL or LDL >150 mg/dl or hypertriglyceridemia (triglyceride >200mg/dL) at screening
8. Laboratory/clinical evidence of: pancreatitis: amylase/lipase >3x upper limit of normal at screening
9. Known current/active infections including HIV, Hepatitis B, Hepatitis C
10. History of cancer, excluding skin cancers (squamous cell or basal cell that have been treated)
11. Known active tuberculosis or untreated tuberculosis
12. Hemoglobin < 8 g/dL
13. Expectation by the investigator to increase corticosteroid or immunosuppressive, or immunomodulatory medication dose at screening, baseline, or over the course of the study
14. Pregnancy or lactation
15. Consumption of > 2 cups of grapefruit juice per day
16. Treatment with medications metabolized using the cytochrome P3A4 pathway, such as cyclosporine, tacrolimus, gemfibrozil, niacin, itraconazole, ketoconazole, erythromycin, azithromycin, clarithromycin, bosentan, nefazodone, tricyclic antidepressants
17. Any condition that, in the opinion of the Investigator, would jeopardize the subject's safety following exposure to the study drug.