Intervention: Nelfinavir
Trial phase: Phase 2
ATC code: J05AE04
SMILES: [H][C@@]12CCCC[C@]1([H])CN(C[C@@H](O)[C@H](CSc1ccccc1)NC(=O)c1cccc(O)c1C)[C@H](C(=O)NC(C)(C)C)C2
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 15
Group description: All subjects will be dosed with nelfinavir 750 mg orally three times daily. This dose may be decreased to 750 mg twice daily if not tolerated. For both stages of the trial the dosing period is 8 weeks followed by a 4 week observation period.

A maximum of 13 subjects will be enrolled in Stage 1. From the 13 subjects enrolled in Stage 1; if 3 or fewer subjects achieve a Response (a ≥35% reduction in serum anti-dsDNA antibody titer), the trial will be terminated. If 4 or more subjects achieve a Response, the study will be expanded to enroll an additional maximum of 30 patients in Stage 2.
Eligibility criteria:
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.