Double-Blinded, Randomized, Placebo-Controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Biochemical Activity of Intravenous Cpn10 Administration in Subjects With Mild to Moderate SLE.

Inclusion criteria

(ALL must be met):

To be entered on study, subjects must meet the following criteria:

• Male or female
• Age 18 - 75 years
• Patients fulfilling at least 4 criteria for SLE as defined by the American College of Rheumatology (ACR)
• Laboratory values as follows:

Documented ANA titer ≥ 1:160 or positive anti-dsDNA antibodies at, or any time prior to screening (verifiable laboratory result)

• Not pregnant or breast-feeding
• If corticosteroids are required for disease stability prior to study entry, able to tolerate a stable dose of ≤ 0.3 mg/kg/day of prednisone or equivalent for the duration of the study.
• Agreement to use an effective form of contraception for the duration of the study.
• Ability to understand and give consent.
• Willing to participate and able to comply with the study requirements, procedures and visits.

Mild SLE only

• Present with mild active SLE disease

Moderate SLE only

• Present with active SLE disease based on SLE disease activity score (SLEDAI) ≥4 and ≤10
• MCP-1 urinary level > 35 pg/ml
• IL-6 serum level > 10 pg/ml
• Meets the American College of Rheumatology (ACR) conditions for "renal disorder" as one of the diagnostic criteria for SLE i.e.

• Persistent proteinuria between 0.5 and 1.0 grams per day or > than 3+ by dipstick OR
• Cellular casts--may be red cell, hemoglobin, granular, tubular, or mixed

OR

• Physician (Pathologist) diagnosis of lupus nephritis of no greater severity than:

• Class I - Minimal mesangial lupus nephritis, OR
• Class II - Mesangial proliferative lupus nephritis, in accordance with the International Society of Nephrology (ISN) and the Renal Pathology Society (RPS) 2003 histological classification.

With diagnosis made ≥ 6 months prior to study commencement.

• If inclusion criteria #15 is met, subject must be receiving stable Standard of Care, including hydroxychloroquine, treatment appropriate for class I-II nephritis.

Exclusion criteria

(NONE can apply):

• Active severe SLE flare with central nervous system (CNS) and/or renal manifestations, pericarditis, active pleuritis, active peritonitis or other SLE manifestations requiring treatment not allowed by the study protocol within 4 weeks of screening
• Pregnant or breast-feeding
• Lack of peripheral venous access.
• History of cardiovascular disease. An acute cardiovascular event within 12 months of study entry, including arterial or venous thrombosis (blood clots).
• Requirement for a stable dose of corticosteroid >0.3 mg/kg/day of prednisone or equivalent.
• Active therapy with human or murine monoclonal antibodies (i.e. belimumab), within 2 months of study entry.
• Any experimental therapy within 3 months of study entry.
• Therapy with cyclophosphamide p.o or parenteral; pulse methylprednisolone or IVIG within 4-6 weeks.
• Subjects being treated with sulfonylureas.
• Subjects with any the following laboratory abnormalities: serum creatinine >3.0 mg/dL, WBC <3,500/μL, ANC <3,000/μL, absolute lymphocyte count ≤500/μL, Hgb <8.0 g/dL, platelets <50,000/μL, ALT and/or AST >1.5 x upper limit of normal (ULN), alkaline phosphatase >1.5 ULN.
• Personal or psychiatric condition that precludes the subject being able to comply with the study requirements or understand and agree to the informed consent process.
• Recent systemic bacterial, fungal, viral, or parasitic infections. Have required management/treatment or hospitalization for any infection within the last 4 weeks before screening.
• History of malignancy - except completely excised basal cell carcinoma.
• Impaired hepatic function
• Body weight of 260lbs/120kg or more (BMI > 35)
• History of tuberculosis (TB) or active, continuing treatment for TB
• History of or current alcohol or substance abuse

Mild SLE only

• Active lupus nephritis and/or severe renal impairment (estimated or measured GFR < 50% predicted for age and gender)

Moderate SLE only

• Subjects with recently diagnosed lupus nephritis (diagnosis made <6 months prior to commencement of study
• Subjects with active urinary sediment