Nelfinavir in Systemic Lupus Erythematosus
Condition: Systemic Lupus Erythematosus
MeSH terms: Lupus Erythematosus, Systemic
Intervention: Nelfinavir
Intervention MeSH terms: Nelfinavir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: lupus; SLE

Summary:

      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.
    

Eligibility criteria:

        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.