A Pilot Study of CC-220 to Treat Systemic Lupus Erythematosus.

NCT ID: NCT02185040

Last Updated: 2020-03-19

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

42 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-09-16

Study Completion Date

2018-09-25

Brief Summary

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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.

Detailed Description

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The study consists of 2 parts. Part 1 is a randomized, double-blind, placebo controlled, ascending dose study to evaluate the safety and tolerability of CC-220 in 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. In each dosing arm, 8 subjects will receive active drug and 2 subjects will receive placebo. 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. A subject will be permitted to reduce their dose one time during Part 1 of the study.

Part 2 is the Active Treatment Extension Phase (ATEP) which is an extension to evaluate the long-term efficacy and safety/tolerability of CC-220 in SLE subjects who completed Part 1 of the study. Subjects who complete the Treatment Phase of Part 1 of the 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 either 0.3 mg QD or 0.6 mg and 0.3 mg QD on alternating days. Subjects who terminate the Treatment Phase of Part 1 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

Conditions

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Systemic Lupus Erythematosus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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CC-220 0.3mg Every Other Day (QOD)

Part 1: CC-220 0.3mg capsules by mouth every other day (QOD)

Group Type EXPERIMENTAL

CC-220

Intervention Type DRUG

0.3 mg oral capsules once every other day with or without food

CC-220 0.3mg Every Day (QD)

* Part 1: CC-220 0.3mg capsules by mouth every day (QD)
* ATEP: CC-220 0.3 mg capsules by mouth every day (QD)

Group Type EXPERIMENTAL

CC-220

Intervention Type DRUG

Subjects will receive 0.3 mg oral capsules every day with or without food

CC-220 0.6mg/0.3mg alternating dose QD

* Part 1: CC-220 0.6 mg and 0.3mg capsules PO on alternating days
* ATEP:CC-220 0.6 mg and 0.3 mg capsules PO on alternating days

Group Type EXPERIMENTAL

CC-220

Intervention Type DRUG

CC-220 oral capsules 0.6 mg and 0.3 mg on alternating days with or without food

CC-220 0.6mg QD

Part 1: CC-220 0.6mg capsules by mouth QD

Group Type EXPERIMENTAL

CC-220

Intervention Type DRUG

CC-220 oral capsule 0.6 mg QD with or without food

Placebo QD

Part 1: Identically matching placebo capsules PO QD

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Matching oral placebo daily

Interventions

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CC-220

0.3 mg oral capsules once every other day with or without food

Intervention Type DRUG

CC-220

Subjects will receive 0.3 mg oral capsules every day with or without food

Intervention Type DRUG

CC-220

CC-220 oral capsules 0.6 mg and 0.3 mg on alternating days with or without food

Intervention Type DRUG

CC-220

CC-220 oral capsule 0.6 mg QD with or without food

Intervention Type DRUG

Placebo

Matching oral placebo daily

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Celgene

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Shimon Korish, M.D.

Role: STUDY_DIRECTOR

Celgene

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Arizona Arthritis and Rheumatology Research, PLLC

Paradise Valley, Arizona, United States

Site Status

University of Arizona Clinical and Translational Science Research Center

Tucson, Arizona, United States

Site Status

UCSD Center for Innovative Therapy

La Jolla, California, United States

Site Status

Dermatology Research Associates

Los Angeles, California, United States

Site Status

East Bay Rheumatology Medical Group Inc.

San Leandro, California, United States

Site Status

Clinical Science Institute

Santa Monica, California, United States

Site Status

Los Angeles Biomedical Research Institute at Harbor - UCLA

Torrance, California, United States

Site Status

Inland Rheumatology Clinical Trials

Upland, California, United States

Site Status

Vipul Joshi, MD, PA, dba Bay Area Arthritis and Osteoporosis

Brandon, Florida, United States

Site Status

Emory University School of Medicine

Atlanta, Georgia, United States

Site Status

Advanced Medical Research

Atlanta, Georgia, United States

Site Status

Arthritis Research and Treatment Center

Stockbridge, Georgia, United States

Site Status

Northwestern Medical Group; Department of Dermatology

Chicago, Illinois, United States

Site Status

Northshore University Health System

Skokie, Illinois, United States

Site Status

Southern Illinois University School of Medicine

Springfield, Illinois, United States

Site Status

Tulane University Health Sciences Center

New Orleans, Louisiana, United States

Site Status

Northwell Health / Division of Rheumatology

Lake Success, New York, United States

Site Status

Feinstein Institute For Medical Research

Manhasset, New York, United States

Site Status

NYU Langone Medical Center

New York, New York, United States

Site Status

Columbia Presbyterian Medical Center

New York, New York, United States

Site Status

Univ of Rochester Medical Center

Rochester, New York, United States

Site Status

DJL Clinical Research

Charlotte, North Carolina, United States

Site Status

MetroHealth Medical Systems

Cleveland, Ohio, United States

Site Status

Ohio State University Medical Center

Columbus, Ohio, United States

Site Status

University of Toledo Medical Center

Toledo, Ohio, United States

Site Status

Oklahoma Medical Research Foundation

Oklahoma City, Oklahoma, United States

Site Status

Altoona Center for Clinical Research

Duncansville, Pennsylvania, United States

Site Status

University of Pennsylvania Health Systems

Philadelphia, Pennsylvania, United States

Site Status

UMPC Lupus Center of Excellence

Pittsburgh, Pennsylvania, United States

Site Status

Low Country Rheumatology PA

Charleston, South Carolina, United States

Site Status

Austin Regional Clinic

Austin, Texas, United States

Site Status

University of Texas Health Science Center at Houston

Houston, Texas, United States

Site Status

Virginia Clinical Research, Inc.

Norfolk, Virginia, United States

Site Status

Seattle Arthritis Clinic

Seattle, Washington, United States

Site Status

Countries

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United States

References

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Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.

Reference Type DERIVED
PMID: 33687069 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan: CC-220-SLE-001-SAP-Part1_Redacted25July2016

View Document

Document Type: Statistical Analysis Plan: CC-220-SLE-001-ATEP.31Oct2018_Redacted

View Document

Other Identifiers

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CC-220-SLE-001

Identifier Type: -

Identifier Source: org_study_id

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