A study to measure how safe CC-220 is and how well CC-220 works in people with lupus.

• Register: EUCTR
• Last refreshed on: 26 October 2021
• Main ID: EUCTR2016-004574-17-BE
• Date of registration: 07/06/2017
• Prospective Registration: Yes
• Primary sponsor: Celgene Corporation
• Public title: A study to measure how safe CC-220 is and how well CC-220 works in people with lupus.
• Scientific title: A PHASE 2, MULTICENTER, RANDOMIZED, DOUBLEBLIND, PLACEBO-CONTROLLED STUDY TO EVALUATE THE EFFICACY AND SAFETY OF CC-220 IN SUBJECTS WITH ACTIVE SYSTEMIC LUPUS ERYTHEMATOSUS
• Date of first enrolment: 14/11/2017
• Target sample size: 280
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-004574-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Belgium, Brazil, Canada, Colombia, France, Germany, Hungary, Italy, Mexico, Poland, Russian Federation, Serbia, Spain, United States

Contacts

• Name: ClinicalTrialDisclosure
• Affiliation: Celgene Corporation

• Name: ClinicalTrialDisclosure
• Affiliation: Celgene Corporation

Key inclusion & exclusion criteria

Inclusion criteria:
•Male or female 18 years of age or older at the time of signing the informed consent.
•Understand and voluntarily sign informed consent forms (ICFs) prior to the initiation of any study specific assessments/procedures.
•Able and willing to adhere to the visit schedule and other protocol requirements.
Disease Specific
•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 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 (items 1-7) 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.
Pregnancy
All male and female subjects should be counseled about pregnancy precautions and risks of fetal exposure as described in the Pregnancy Prevention Plan (provided separately).
•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 abstinence 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 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
Exclusion criteria:
1.The subject has received:
a.Cyclophosphamide within 3 months of the Baseline Visit. Previous use of Melphalan or other alkylating agents is prohibited.
b.Etanercept within 4 weeks prior to the Baseline Visit.
c.Belimumab within 3 months prior to the Baseline Visit.
d.B-cell depleting or modulating agents, such as rituximab or anti-CD22 therapy, within one year prior to the Baseline Visit.
e.Any other biologic or non-biologic immunosuppressive agent within 2 months of 5 pharmacokinetic half-lives (whichever is longer) prior to the Baseline Visit.
2.The subject has been treated with intra-articular, intralesional, subcutaneous, intradermal, intramuscular or IV pulse corticosteroids 6 weeks prior to the Baseline Visit.
3.The subject has received high potency topical corticosteroids within two weeks of the Screening Visit (only Class 6 or 7 are permitted).
4.The subject has undergone plasmapheresis within 3 months of the Baseline Visit.
5.The subject has received IV immunoglobulin within 3 months of the Baseline Visit.
6.The subject has received strong inhibitors or inducers of CYP3A4/5 including grapefruit, St. John’s Wort or related products within two weeks prior to the Baseline Visit.
7.The subject has a planned or received immunization with a live or live attenuated vaccine within 2 months prior to the Baseline Visit and for 2 months after administration of the last dose of IP.
Disease Severity
8.The subject has 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.
9.The subject has active, severe or unstable neuropsychiatric lupus disease (e.g., poorly controlled seizure disorder, acute confusional state, myelitis, stroke or stroke syndrome, cerebellar ataxia or dementia related to SLE, psychosis, organic brain syndrome, cerebrovascular accident [CVA], cerebritis or CNS vasculitis), within 6 months of the Screening Visit.
Concomitant Disease
10.The subject has QTcF of > 450 milliseconds.
11.The subject has a history of hepatitis B and/or hepatitis C.
12.The subject has a confirmed positive test for Hepatitis B or Hepatitis C during the Screening Phase. Subjects with isolated positive hepatitis B surface antibody are not excluded.
13.The subject has a history of congenital and/or acquired immunodeficiencies (eg, common variable immunodeficiency, human immunodeficiency virus [HIV], etc).
14.The subject has 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.
15.The subject has a history of latent or active TB, unless there is medical record documentation of successful completion of a standard course of treatment per local guidelines.
16.The subject has an abnormal chest radiograph with evidence of active infection or possible malignancy. Alternatively, PA or PA/lateral radiographs that were taken within the 3 months (or longer periods based on local health authority requirements) prior to the Screening Visit will be accepted for evaluation for participation in the study.
17.The subject has malignancy or history of malignancy, except for:
•treated (e

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

SYSTEMIC LUPUS ERYTHEMATOSUS
MedDRA version: 20.0 Level: LLT Classification code 10025134 Term: Lupus erythematosus System Organ Class: 100000004859

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Code: CC-220
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: CC-220
Other descriptive name: CC-220
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.15-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Code: CC-220
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: CC-220
Other descriptive name: CC-220
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.3-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Code: CC-220
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: CC-220
Other descriptive name: CC-220
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.45-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: To evaluate the clinical efficacy of three doses of CC-220 (0.45 mg once per day [QD], 0.3 mg QD or 0.15 mg QD) compared to placebo, for the treatment of active systemic lupus erythematosus (SLE) using the SLE Responder Index at Week 24, defined as:
- Reduction from baseline of = 4 points in the SLEDAI 2K and
- No new one or more British Isles Lupus Assessment Group (BILAG) A or new* 2 or more BILAG B items compared to baseline using BILAG 2004 Index and
- No worsening from baseline defined by an increase of < 0.30 points from baseline on a Physician's Global Assessment (PGA) visual analog scale (VAS) from 0-3
*new excludes A to B

Secondary Objective: Week 24
- To evaluate additional measures of clinical disease activity of CC-220 (0.45 mg once per day [QD], 0.3 mg QD or 0.15 mg QD) compared to placebo for the treatment of subjects with active SLE
- To assess the reduction in steroid use
- To evaluate the safety and tolerability of 0.45 mg QD, 0.3 mg QD, and 0.15 mg QD of CC-220 compared to placebo in subjects with active SLE
Week 52
-To evaluate additional measures of clinical disease activity and maintenance of effect of CC-220 (0.45 mg once per day [QD], 0.3 mg QD or 0.15 mg QD) for the treatment of subjects with active SLE
- To assess the reduction in steroid use
- To evaluate the longer term safety and tolerability of 0.45 mg QD, 0.3 mg QD, and 0.15 mg QD of CC-220 in subjects with active SLE

Primary end point(s): SRI(4) response

Timepoint(s) of evaluation of this end point: Week 24

Secondary Outcome(s)

Secondary end point(s): SRI(4)
SLEDAI 2K
CLASI
BILAG
Joint Counts
PGA
Fatigue
BILAG
Corticosteroid Reduction
Flare
SLE Damage

Timepoint(s) of evaluation of this end point: SRI(4): Week 52
SLEDAI 2K: Week 24 and Week 52
CLASI: Week 24 and Week 52
BILAG: Week 24 and Week 52
Joint Counts: Week 24 and Week 52
PGA: Week 24 and Week 52
Fatigue: Week 24 and Week 52
BILAG: Week 24 and Week 52
Corticosteroid Reduction: Week 24 and Week 52
Flare: All visits
SLE Damage: Week 52

Secondary ID(s)

2016-004574-17-ES

CC-220-SLE-002

NCT03161483

Source(s) of Monetary Support

Celgene Corporation

Ethics review

Status: Approved
Approval date: 28/11/2017
Contact: