A 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.
- Lupus Erythematosus, Systemic
- Eligible Ages
- Over 18 Years
- Eligible Genders
- Accepts Healthy Volunteers
- Male or female 18 years of age or older at the time of signing the informed consent.
- Able and willing to adhere to the visit schedule and other protocol requirements.
- 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.
- At the Screening Visit a Systemic Lupus Erythematosus Disease Activity Index (2K) (SLEDAI 2K) score of ≥ 6 points, at least four points of which are a "clinical" SLEDAI 2K score. The "clinical" score is the SLEDAI 2K assessment score without the inclusion of points attributable to any urine or blood laboratory results including immunologic measures. Neurologic descriptors of the SLEDAI 2K are not counted towards the SLEDAI study entry criteria.
- At the Baseline Visit, a clinical SLEDAI 2K score of ≥ 4 points.
Positive antibodies associated with SLE, which must include at least one of the following within the Screening Phase:
- Positive antinuclear antibody (ANA) test at the central laboratory with a titer of 1:80 or greater, associated with a diagnosis of SLE, Anti-dsDNA antibodies elevated to above normal as per the central laboratory,
- Anti-Smith (anti-Sm) antibody elevated to above normal as per the central laboratory.
6. Females of childbearing potential (FCBP) must:
- Have two negative pregnancy tests as verified by the investigator prior to starting study therapy, one within 10 to 14 days prior to the first dose of CC-220 and again within 24 hours before taking the first dose of CC-220. She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. This applies even if the subject practices true abstinence from heterosexual contact.
- Either commit to true abstinence2 from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use two forms of reliable contraception simultaneously. One must be a highly effective method and one additional effective (barrier) method, and both must be practiced without interruption, 28 days prior to starting investigational product, during the study therapy (including dose interruptions), and for 28 days after discontinuation of study therapy.
- Male subjects must: Practice true abstinence or agree to use a barrier contraception (male latex condom or non-latex condom NOT made out of natural [animal] membrane [for example, polyurethane]) during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 90 days following investigational product discontinuation, even if he has undergone a successful vasectomy.
- Male subjects must agree not to donate semen or sperm during therapy and for at least 90 days following the discontinuation of Investigational Product (IP).
7. 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.
- Agree not to share IP with another person.
- Other than the subject, FCBP and males able to father a child should not handle the IP or touch the capsules unless gloves are worn.
- Be counseled about pregnancy precautions and risks of fetal exposure as described in the Pregnancy Prevention Plan.
8. If taking oral corticosteroids, must be on for at least 4 weeks prior to the Screening Visit, and maintained on a stable dose of ≤ 20 mg/d of prednisone or equivalent for at least 2 weeks prior to the Baseline Visit.
9. If taking SLE standard of care treatment (e.g. anti-malarial, mycophenolate mofetil, azathioprine) for 12 weeks prior to and be on a stable dose for at least 4 weeks prior to Baseline.
- Must be off prohibited medications for a pre-specified period of time.
- Received intra-articular, intralesional, subcutaneous, intradermal, intramuscular or IV pulse corticosteroids 6 weeks prior to the Baseline Visit.
- Received an investigational product within 5 pharmacokinetic half-lives or one month, whichever is longer, prior to the Baseline Visit.
- Severe lupus nephritis defined as: estimated glomerular filtration rate (eGFR) of < 45 mL/1.73 m2 or proteinuria > 2000 mg/day if stable for the past 3 months or proteinuria > 500 mg/day if unstable.
- Proteinuria will be based upon spot urine testing.
- Active, severe or unstable neuropsychiatric lupus disease within 6 months of the Screening Visit.
- History or confirmed positive test for hepatitis B History of congenital and/or acquired mmunodeficiencies (eg, common variable immunodeficiency, human immunodeficiency virus [HIV], etc).
- 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.
- Active tuberculosis (TB) or a history of incompletely treated TB, or a positive, QuantiFERON®-TB Gold test.
- 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 or carcinoma in situ of the cervix with no evidence of recurrence within 5 years of the Screening Visit.
- Any subject who:
a. has a diagnosis or history consistent with Antiphospholipid Syndrome (APS) b. has "triple positivity" (ie, a positive lupus anticoagulant, anticardiolipin, and anti-B2 glycoprotein). Subjects with antiphospholipid antibodies without a diagnosis of APS will be reviewed by the adjudication committee for entry into the study based on the titer, the number of positive antibodies, and other risk factors.
c. is unwilling or unable to undergo protocol required thromboprophylaxis. The subject has history of arterial or venous thrombosis, unless the subject is on appropriate anticoagulation for at least 6 months prior to the Baseline Visit and throughout the study. Superficial phlebitis may be discussed with the medical monitor.
12. History or current diagnosis of peripheral neuropathy (sensory or motor) ≥ Grade 2.
13. Presence of active uveitis or any other ophthalmological finding that in the opinion of the Investigator is clinically significant.
14. Other non-SLE driven inflammatory joint or skin disease or overlap syndromes as the primary disease.
15. Clinically significant or unstable or uncontrolled acute or chronic disease not due to SLE
16. Does not meet required laboratory criteria.
17. Pregnant or a breast-feeding female.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply
- Phase 2
- Study Type
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
CC-220 0.45 mg QD Placebo Controlled Phase
|At Weeks 0 to 24: CC-220 Placebo Controlled Phase: CC-220 0.45 mg once daily (QD) At Weeks 24 to 52: CC-220 Active Treatment Phase: CC-220 0.45 mg once daily (QD)||
C-220 0.3 mg QD Placebo Controlled Phase
|At Weeks 0 to 24: CC-220 Placebo Controlled Phase: CC-220 0.3 mg once daily (QD) At Weeks 24 to 52: CC-220 Active Treatment Phase: CC-220 0.30 mg once daily (QD)||
CC-220 0.15 mg QD Placebo Controlled Phase
|At Weeks 0 to 24: CC-220 Placebo Controlled Phase: CC-220 0.15 mg once daily (QD) At Weeks 24 to 52: CC-220 Active Treatment Phase: CC-220 0.15 mg once daily (QD)||
|Weeks 0 to 24: CC-220 Placebo Controlled Phase: placebo once daily (QD)||
- NCT ID
Study ContactAssociate Director Clinical Trial Disclosure
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.
- 4-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.