A Study to Evaluate the Efficacy and Safety of CC-220 in Subjects With Active Systemic Lupus Erythematosus

A PHASE 2, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO EVALUATE THE EFFICACY AND SAFETY OF CC-220 IN SUBJECTS WITH ACTIVE SYSTEMIC LUPUS ERYTHEMATOSUS

The purpose of this Phase 2, multicenter, randomized, placebo-controlled, double-blind study to evaluate the efficacy and safety of an oral treatment regimen of CC-220 versus placebo in adult subjects with active systemic lupus erythematosus.

Approximately 280 subjects with a documented diagnosis of SLE will be randomized 2:2:1:2 to receive CC-220 (0.45 mg QD, 0.3 mg QD or 0.15 mg QD) or identically appearing placebo.

The study consists of four phases:

• 4-week Screening Phase
• 24-week placebo-controlled phase Subjects will receive either 0.45 mg QD, 0.3 mg QD, 0.15 mg QD or placebo for the first 24 weeks of treatment.
• 28-week active treatment phase At Week 24, all subjects on placebo will be re-randomized to active treatment.
• 52-week long-term extension phase Subjects who complete the treatment phase may be eligible to roll over into a Long-term Extension of up to 52 weeks of treatment.
• 4 - 12-week observational follow-up All subjects who complete 52 weeks of treatment or discontinue the study early will enter a post-treatment observation follow-up phase. The Observational Follow-up Phase will consist of one visit 4 weeks following cessation of study drug for all subjects with an additional 12-week Observational Follow-up visit for males only.

Inclusion Criteria:

• Male or female 18 years of age or older at the time of signing the informed consent.

• Have a diagnosis of SLE for at least 6 months prior to the Screening Visit and fulfill the 1997 update of the 1982 American College of Rheumatology (ACR) Classification Criteria for SLE at the Screening Visit.

• A SLEDAI 2K score of ≥ 6 points, WITH at least 4 points being a "clinical" SLEDAI 2K score. The "clinical" score excludes points attributable to any urine or blood laboratory results including immunologic measures.

• At the Baseline Visit, a clinical SLEDAI 2K score of ≥ 4 points.

• Have at least one of the following positive antibodies associated with SLE per the central laboratory within the Screening Phase:

  • Positive antinuclear antibody (ANA) test at the central laboratory with a titer of 1:40 or greater, associated with a diagnosis of SLE,
  • Anti-dsDNA antibodies elevated to above normal
  • Anti-Smith (anti-Sm) antibody elevated to above normal

• Females of childbearing potential must: Have two negative pregnancy tests as verified by the Investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment.

  o Either commit to true abstinence from heterosexual contact or agree to use two forms of reliable contraception simultaneously.

• Male subjects must: Practice true abstinence or agree to use a barrier contraception during sexual contact.

All subjects must:

• Understand that the IP could have potential teratogenic risk.

• Agree to abstain from donating blood while taking IP and for 28 days following discontinuation of the IP.

  • Have been treated with at least one of the following SLE medications prior to the Screening Visit: antimalarials, immunosuppressants, and/or corticosteroids.
  • Currently receiving stable doses of at least one of the following medications: systemic corticosteroids, antimalarials, and/or immunosuppressants.

Exclusion Criteria:

• Received intra-articular, intralesional, subcutaneous, intradermal, intramuscular or IV pulse corticosteroids 6 weeks prior to the Baseline Visit.

• Received any other biologic or non-biologic immunosuppressive agent within 2 months of 5 pharmacokinetic half-lives (whichever is longer) prior to the Baseline Visit.

• Have severe lupus nephritis defined as: estimated glomerular filtration rate of < 45 mL/1.73 m2 or proteinuria > 2000 mg/day based on protein to creatinine ratio, or active lupus nephritis that may require 'induction' therapy

• Have active, severe or unstable neuropsychiatric lupus disease within 6 months of the Screening Visit.

• Have serologic tests consistent with infection with either hepatitis B or hepatitis C, and/or confirmed history of hepatitis B or hepatitis C infection.

• Have history of congenital and/or acquired immunodeficiencies (eg, common variable immunodeficiency, human immunodeficiency virus, etc).

• Have active or history of recurrent bacterial, viral, fungal, mycobacterial or other infections, or any major episode of infection requiring hospitalization or treatment with intravenous or oral antibiotics within 4 weeks of the Screening Visit and at any time during the Screening Phase, up through the first dose of IP.

• Have active tuberculosis or a history of latent or active tuberculosis

• Have malignancy or history of malignancy, except for:

  • treated (eg, cured) basal cell or squamous cell in situ skin carcinomas
  • treated (eg, cured) cervical intraepithelial neoplasia Grade 1 and Grade 2
  • treated (eg, cured) carcinoma in situ of the cervix with no evidence of recurrence within 5 years of the Screening Visit.

• Have a diagnosis or history consistent with Antiphospholipid Syndrome or "triple antiphospholipid positivity" (ie, positive lupus anticoagulant, anticardiolipin, and anti-B2 glycoprotein).

• Have history of arterial or venous thrombosis

• Have history or current diagnosis of peripheral neuropathy (sensory or motor) ≥ Grade 2.

• Have presence of active uveitis or any other ophthalmological finding that in the opinion of the Investigator is clinically significant.

• Have other non-SLE driven inflammatory joint or skin disease or overlap syndromes as the primary disease.

• Have clinically significant or unstable or uncontrolled acute or chronic disease not due to SLE

• Does not meet required laboratory criteria.

• Does not meet pre-specified periods for prohibited medications.

• Pregnant or a breast-feeding female.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply