A Pilot Study of CC-220 to Treat Systemic Lupus Erythematosus.
Condition: Systemic Lupus Erythematosus
MeSH terms: Lupus Erythematosus, Systemic
Intervention: CC-220; CC-220; CC-220; CC-220; Placebo
Intervention description: 0.3 mg oral capsules once every other day with or without food; Subjects will receive 0.3 mg oral capsules every day with or without food; CC-220 oral capsules 0.6 mg and 0.3 mg on alternating days with or without food; CC-220 oral capsule 0.6 mg QD with or without food; Matching oral placebo daily
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 42.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Lupus, Systemic Lupus, SLE

Summary:

      The purpose of this study is to determine whether CC-220 is effective for the treatment of
      skin, joint and serological manifestations of systemic lupus erythematosus.
    

Eligibility criteria:

        Inclusion Criteria:

        Part 1

          -  The subject has an established diagnosis of systemic lupus erythematosus (SLE) as
             defined by the 1997 Update of the 1982 ACR Revised Criteria for Classification of SLE
             at screening. The diagnosis is fulfilled provided that at least 4 criteria are met.

          -  Disease history of SLE ≥ 6 months at baseline

          -  Females of childbearing potential (FCBP) must:

               -  Have two negative pregnancy tests as verified by the study doctor prior to
                  starting study therapy. She must agree to ongoing pregnancy testing during the
                  course of the study, and after end of study therapy. This applies even if the
                  subject practices true abstinence from heterosexual contact.

               -  Either commit to true abstinence from heterosexual contact (which must be
                  reviewed on a monthly basis) or agree to use, and be able to comply with,
                  effective contraception without interruption, 28 days prior to starting IP,
                  during the study therapy (including dose interruptions), and for 28 days after
                  discontinuation of study therapy.

          -  Male subjects must:

               -  Must practice true abstinence or agree to use a condom 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 28 days following IP
                  discontinuation, even if he has undergone a successful vasectomy.

               -  If the subject is using oral corticosteroids, the daily dose must be less than or
                  equal to 10 mg of prednisone or equivalent during the study; the dose must be
                  stable over the 4 weeks preceding screening and throughout the study.

               -  All subjects taking hydroxychloroquine, chloroquine and/or quinacrine during the
                  study must have documentation of a normal ophthalmologic examination performed
                  within 1 year of the Baseline Visit.

               -  For subjects not taking corticosteroids, or antimalarials, the last dose (in case
                  of previous use) must be at least 4 weeks prior to screening.

        ATEP

          -  Male or female 18 years of age or older

          -  Understand and voluntarily sign an ICD prior to the initiation of any study related
             assessments/procedures

          -  Able to adhere to the study visit schedule and other protocol requirements. Pregnancy

          -  Females of childbearing potential (FCBP) must:

               -  Have two negative pregnancy tests as verified by the study doctor prior to
                  starting study therapy. She must agree to ongoing pregnancy testing during the
                  course of the study, and after end of study therapy. This applies even if the
                  subject practices true abstinence* from heterosexual contact.

               -  Either commit to true abstinence* from heterosexual contact (which must be
                  reviewed on a monthly basis) or agree to use, and be able to comply with,
                  effective contraception without interruption, 28 days prior to starting IP,
                  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 condom 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 28 days following IP
             discontinuation, even if he has undergone a successful vasectomy. True abstinence is
             acceptable when this is in line with the preferred and usual lifestyle of the subject.
             (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods]
             and withdrawal are not acceptable methods of contraception.)

          -  Male subjects must agree not to donate semen or sperm during therapy and for at least
             90 days following the discontinuation of IP.

          -  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. Concomitant Medications

          -  If the subject is using oral corticosteroids, the daily dose must be less than or
             equal to 10 mg of prednisone or equivalent during the study; the dose must be stable
             over the 4 weeks preceding randomization and throughout the study.

          -  All subjects taking hydroxychloroquine, chloroquine or quinacrine during the study
             must have documentation of a normal ophthalmologic examination performed within 1 year
             of the Baseline Visit.

          -  For subjects not taking corticosteroids the last dose (in case of previous use) must
             be at least 4 weeks prior to screening.

        Exclusion Criteria

          -  The subject has been treated with intra-articular, intramuscular or IV pulse
             corticosteroids within 4 weeks of screening.

          -  The subject has received high dose oral prednisone (> 100 mg/day) within 4 weeks of
             screening.

          -  The subject has received cyclophosphamide, azathioprine or mycophenolate mofetil
             within 12 weeks of screening.

          -  The subject has participated in a clinical trial and has received an investigational
             product within 30 days, 5 pharmacokinetic half-lives or twice the duration of the
             biological effect of the investigational product (whichever is longer) prior to
             screening; OR participation in two or more investigational drug trials within 12
             months of screening.

          -  Unstable lupus nephritis defined as: proteinuria > 1.0 g/24 hour /1.73 m2 OR eGFR of
             less than 60 mL/1.73 m2 CNS disease, including active severe CNS lupus (including
             seizures, psychosis, organic brain syndrome, cerebrovascular accident (CVA),
             cerebritis or CNS vasculitis) requiring therapeutic intervention within 6 months of
             screening.

          -  The subject has New York Heart Association (NYHA) Class III or IV congestive heart
             failure.

          -  Presence of hepatitis B surface antigen (HBsAG). Subjects may have a positive
             anti-hepatitis B core antibody (anti-HBc) if the anti-hepatitis B surface antibody
             (anti-HBs) is positive as well.

          -  Antibodies to hepatitis C at Screening.

          -  The subject has a known positive history of antibodies to human immunodeficiency virus
             (HIV) or HIV disease or acquired immune deficiency syndrome (AIDs).

          -  Has a history of an organ transplant (e.g., heart, lung, kidney, liver) or
             hematopoietic stem cell/marrow transplant.

          -  Malignancy or history of malignancy, except for:

               -  treated (ie, cured) basal cell or squamous cell in situ skin carcinomas;

               -  treated (ie, cured) cervical intraepithelial neoplasia (CIN) or carcinoma in situ
                  of the cervix with no evidence of recurrence within 5 years of Screening

          -  Systemic bacterial infections requiring treatment with oral or injectable antibiotics,
             or significant viral or fungal infections, within 4 weeks of Screening. Any treatment
             for such infections must have been completed and the infection cured, at least 2 weeks
             prior to Screening and no new or recurrent infections prior to the Baseline visit.

          -  History of venous thrombosis or any thromboembolic events within 2 years of screening.

          -  Clinical evidence of significant unstable or uncontrolled acute or chronic disease not
             due to SLE (ie, cardiovascular, pulmonary, hematologic, gastrointestinal, hepatic,
             renal, neurological, malignancy, psychiatric or infectious disease) which in the
             opinion of the investigator could put the subject at undue risk or confound study
             results.

          -  Presence of active uveitis or any other clinically significant ophthalmological
             finding.

          -  History or current diagnosis of peripheral or radicular neuropathy. Any clinically
             significant abnormalities on ECG, which, in the opinion of the investigator would
             interfere with safe participation in the study.