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Eligibility
for people ages 18 years and up
Location
at Fresno, California and other locations
Dates
study started
estimated completion:

Description

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.

Official Title

A Pilot, Phase 2, Randomized, Placebo-Controlled, Double-Blind, Study To Evaluate Efficacy, Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Pharmacogenetics of CC-220 In Subjects With Systemic Lupus Erythematosus

Details

The study consists of 3 parts. Part 1 is a randomized, double-blind, placebo controlled, ascending dose study to evaluate the safety and tolerability of CC-220 in Systemic Lupus Erythematosus (SLE) subjects.

Subject participation in Part 1 consists of 3 phases:

  • Pre-treatment Screening Phase: up to 28 days prior to the first dose of the investigational product (IP)
  • Treatment Phase: up to 84 days
  • Observation Phase: 84 day post-treatment A total of approximately 40 subjects will be randomized into 4 dose groups with a 4:1 ratio of CC-220 (0.3 mg every other day [QOD], 0.3 mg everyday [QD], 0.6 mg and 0.3 mg on alternating days and 0.6 mg QD) or matching placebo (8 subjects in the CC-220 arm and 2 subjects in the placebo arm for each dose group). Subjects will be randomized into the first two dose groups of 0.3 mg QOD and 0.3 mg QD in parallel.

Following confirmation of safety of the first two dose groups, remaining subjects will then be randomized into the 0.6 mg and 0.3 mg on alternating days and 0.6 mg QD dose groups in a sequential, dose ascending manner (first the 0.6 mg and 0.3 mg on alternating days dose group followed by the 0.6 mg QD dose group) A subject will only be permitted to reduce their dose one time during the study. The Treatment Phase will be up to 84 days in duration for all dose groups.

Subjects who discontinue IP early and all subjects who complete the 84 day treatment phase will enter into the Observational Follow-up Phase for an 84 day period. In all cases of early termination from the study, subjects will be encouraged to complete an Early Termination Visit.

Part 2 is a randomized, placebo-controlled, double-blind, parallel group study to evaluate the efficacy and safety of CC-220 in SLE subjects with skin involvement. It will only be initiated once up to 8 subjects have completed 28 days of treatment in the 0.6 mg QD dose group for Part 1 and the 28 day safety assessment of the 0.6 mg QD dose group in Part 1 is completed.

Subject participation in Part 2 will consist of 3 phases:

  • Pre-treatment Screening Phase: up to 28 days prior to the start of the IP
  • Treatment Phase: Up to 84 days
  • Observation Phase: 84 day post-treatment Up to a total of approximately 100 subjects will be randomized into 4 dose groups of CC-220 (0.3 mg QOD, 0.3 mg QD, 0.6 mg and 0.3 mg on alternating days and 0.6 mg QD) or matching placebo (20 subjects in each CC-220 dosing arm and 20 subjects in the placebo arm). The dose groups included in Part 2 will be dependent on results from Part 1. Any dose group which does not demonstrate adequate safety, tolerability, PK or PD may not be used in Part 2. The Treatment Phase for Part 2 will be up to 84 days in duration.

Subjects who discontinue IP early and all subjects who complete the 84- day Treatment Phase will enter into the Observational Follow-up Phase for a 84-day period. In all cases of early termination from the study, subjects will be encouraged to complete an Early Termination Visit. Upon completion of, or discontinuation from the Treatment Phase for Part 1 or Part 2, all subjects (including premature discontinuations) will be have visits 28 days and 84 days after their final treatment visit during the 84 day Observational Follow-up Phase.

The Active Treatment Extension Phase (ATEP) is an extension of the core CC-220-SLE-001 study to evaluate the long-term efficacy and safety/tolerability of CC-220 in SLE subjects who completed Part 1 or Part 2 of the core study.

Subjects who complete the Treatment Phase of Part 1 or Part 2 of the core study will be eligible to receive CC-220 in the ATEP for up to 2 years. All subjects who participate in the ATEP will receive the same active treatment they received during their participation in Part 1 or Part 2 with the exception of those on placebo or 0.3 mg every other day (QOD) (see below for information on dosing for these subjects).

Subjects who complete the Treatment Phase of Part 1 or Part 2 of the core study will be eligible to enter this phase of the study and should be enrolled immediately to avoid dose interruption. In the event the ATEP has not been implemented by a subject's study center at the time they have completed the Treatment Phase, subjects will enter the Observation Phase of the core study and be eligible to enroll in the ATEP upon implementation of this amendment. There are no time restrictions on how long subjects can be off CC-220 prior to entering the ATEP as long as they completed treatment in Part 1 or Part 2 of the core study. Subjects who terminate the Treatment Phase of Part 1 or Part 2 early will not be eligible for entry into the ATEP.

Subject participation consists of two phases:

  • Active Treatment Extension Phase: Up to 2 years
  • Observational Follow-up Phase: One month

Keywords

Systemic Lupus Erythematosus Lupus, Systemic Lupus, SLE

Eligibility

You can join if…

Open to people ages 18 years and up

Part 1

  • The subject has an established diagnosis of systemic lupus erythematosus
  • Disease history of SLE ≥ 6 months at baseline
  • Females of childbearing potential (FCBP) must:
  • Have two negative pregnancy tests and must agree to ongoing pregnancy testing during the course of the study, and after end 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,
  • 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
  • Subjects taking hydroxychloroquine, chloroquine and/or quinacrine are required to use the medication for 16 weeks prior to their screening visit and be on a stable dose for at least 4 weeks prior to first dose of IP and throughout the study.
  • For subjects not taking corticosteroids, or antimalarials, the last dose (in case of previous use) must be at least 4 weeks prior to screening.

    Part 2

  • The subject has an established diagnosis of systemic lupus erythematosus
  • Disease history of SLE ≥ 6 months at baseline
  • Subjects must have 3 or greater tender joints at the Baseline visit.
  • Must have cutaneous manifestations of lupus
  • Positive antibodies associated with SLE, which must include one of the following:
  • 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.
  • 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.
  • 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.
  • Subjects taking hydroxychloroquine, chloroquine and/or quinacrine are required to use the medication for 16 weeks prior to their screening visit and be on a stable dose for at least 4 weeks prior to first dose of IP 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 informed consent document (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.
  • 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.
  • 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.
  • 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.

You CAN'T join if...

art 1, Part 2 and ATEP

  • 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 undergone plasmapheresis within 4 weeks of screening
  • The subject has received methotrexate, sulfasalazine, leflunomide, tacrolimus,cyclosporine A, azathioprine, mycophenalate mofetil or iv immunoglobulin (IVIG)within 4 weeks of screening. Note: methotrexate, sulfasalazine or leflunomide will be permitted for concomitant use during the ATEP.
  • Previous use of melphalan.
  • The subject has received cyclophosphamide within 8 weeks of screening.
  • Prior use of benlysta, abatacept, tocilizumab, adalimumab, infliximab, etanercept and other anti-TNF inhibitors within 12 weeks of screening.
  • The subject has been treated with biological therapy (eg, fusion proteins,therapeutic proteins, monoclonal antibodies or antibody fragments) within 8 weeks or 5 half-lives of screening.
  • The subject has received B-cell depleting or modulating agents, such as rituximab or antiCD22 therapy, within 6 months prior to screening OR has received B-cell depleting agents from which the subject's B-cell count has not yet normalized (ie, CD20+ B-cell count is less than 200 and the absolute lymphocyte count [ALC] is less than 1500/μL).
  • St. John's Wort within one month of screening.
  • Strong inhibitors or inducers of CYP3A4/5 at least one week prior to dosing and during the course of study (Please refer to Appendix K for examples of medications).Grapefruit or related products ≤ 1 week prior to dosing and throughout the study.
  • 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.
  • Unwilling to abstain from the use of prescription or non-prescription drugs,including: agents known to interact with CC-220, erythropoietin stimulation factors;herbal and dietary supplements (vitamins are permitted) or alternative medicine during study participation.
  • The subject has a planned or received immunization with a live or live attenuated vaccine within 2 months prior to administration of the first dose of IP and for 2 months after administration of the last dose of IP.
  • Have a planned surgical procedure or a history of any other medical disease laboratory abnormality, or condition that, in the opinion of the investigator, makes the subject unsuitable for the study. Disease Severity
  • Unstable lupus nephritis defined as: eGFR of less than 50 mL/1.73 m2 . 17. 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 antihepatitis B core antibody (anti-HBc) if the anti-hepatitis B surface antibody(anti-HBs) is positive as well (Appendix L). Note: for the ATEP, this exclusion will only apply to those subjects who come in for the ATEP greater than 14 days after their Part 1 or Part 2 Week 12 (Visit 10).
  • Antibodies to hepatitis C at Screening. Note: for the ATEP, this exclusion will only apply for those subjects who come in for the ATEP greater than 14 days after their Part 1 or Part 2 Week 12 (Visit 10).
  • 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 (eg, 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 neuropathy.
  • Hematology: • Neutrophil count ≤ 1.5 x 109 /L (subjects entering the ATEP within 14 days can have a neutrophil count as low as 1.0 x 109 /L) • Hb ≤ 9 g/dL • Lymphocyte count ≤ 500/mm3 or 0.50 x 109 /L • Platelet count ≤ 100 x 109 /L • Serum immunoglobulin (Ig) levels: IgG ≤ the lower limit of normal (LLN) • Liver function tests: - Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 2x upper limit of normal (ULN) - Alkaline phosphatase and bilirubin> 1.5 x ULN(isolated bilirubin> 1.5 ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%). 30. Any clinically significant abnormalities on ECG, which, in the opinion of the investigator would interfere with safe participation in the study.General
  • The subject is unlikely to comply with the study protocol or is unsuitable for any other reason, as judged by the investigator or medical monitor.
  • Substance dependence or abuse within six months of the Screening Visit which, in the opinion of the investigator, would interfere with the patient's safety or ability to comply with the study procedures.
  • History of sensitivity to any of the investigational products/placebo, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation. The subject has a history of severe allergic reactions to or hypersensitivity to any component of the IP or placebo. - History of tuberculosis (TB). Subjects with a history of TB who have completed a standard course of treatment (documented) are eligible for study entry.
  • Pregnant or nursing (breast-feeding) females.

Locations

  • C Michael Neuwelt M D
    San Leandro, California, 94578, United States
  • Dermatology Institute and Skin Care Center
    Santa Monica, California, 90404, United States
  • Dermatology Research Associates
    Los Angeles, California, 90045, United States
  • Inland Rheumatology Clinical Trials
    Upland, California, 91786, United States
  • Los Angeles Biomedical Research Institute at Harbor - UCLA
    Torrance, California, 90502, United States

Details

Status
in progress, not accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Celgene
ID
NCT02185040
Phase
Phase 2
Study Type
Interventional
Last Updated
May 1, 2017