Nelfinavir in Systemic Lupus Erythematosus (NISLE)

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

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.

Study Overview

• Status: Terminated
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Drug: Nelfinavir

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Los Angeles, California, United States, 90095
      • UCLA David Geffen School of Medicine
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • New York
    • Bronx, New York, United States, 10457
      • Bronx Lebanon Hospital
    • Manhasset, New York, United States, 11030
      • The Feinstein Institute for Medical Research
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10016
      • New York University School of Medicine
    • New York, New York, United States, 20021
      • Hospital for Special Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: nelfinavir; Nelfinavir tablets will be taken by oral administration, 750mg (three 250 mg tablets) three times a day	Drug: Nelfinavir; Other Names: Viracept

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Northwell Health
• Collaborators: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
• Investigators: Principal Investigator: Meggan Mackay, MD, Northwell Health

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): June 1, 2018
• Study Completion (Actual): June 1, 2018

Study Registration Dates

• First Submitted: February 12, 2014
• First Submitted That Met QC Criteria: February 14, 2014
• First Posted (Estimate): February 19, 2014

Study Record Updates

• Last Update Posted (Actual): February 24, 2020
• Last Update Submitted That Met QC Criteria: February 21, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: SLE; lupus
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Nelfinavir
• Other Study ID Numbers: NISLE