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A Study to Evaluate the Efficacy and Safety of CC-220 in Subjects With Active Systemic Lupus Erythematosus

This study is not yet open for participant recruitment.
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Verified May 2017 by Celgene
Sponsor:
Information provided by (Responsible Party):
Celgene
ClinicalTrials.gov Identifier:
NCT03161483
First received: May 18, 2017
Last updated: May 23, 2017
Last verified: May 2017
  Purpose

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.


Condition Intervention Phase
Lupus Erythematosus, Systemic Drug: CC-220 Other: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Treatment
Official Title: A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Study to Evaluate the Efficacy and Safety of CC-220 in Subjects With Active Systemic Lupus Erythematosus

Resource links provided by NLM:


Further study details as provided by Celgene:

Primary Outcome Measures:
  • Proportion of subjects who achieve SRI(4) response- Week 24 [ Time Frame: Week 24 ]

    SRI(4) is a composite endpoint, defined by the following criteria:

    • Reduction from baseline of ≥ 4 points in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2K score 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


Secondary Outcome Measures:
  • Proportion of subjects who achieve SRI(4) response - Week 52 [ Time Frame: Week 52 ]

    SRI(4) is a composite endpoint, defined by the following criteria:

    • Reduction from baseline of ≥ 4 points in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2K score 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

  • Proportion of subjects with SLEDAI 2K score improvement of ≥ 4 points from Baseline [ Time Frame: Weeks 24 and 52 ]
    The SLEDAI 2K score measures disease activity through assessment of 24 lupus manifestations using a weighted score of 1 to 8 points. A manifestation is recorded if it is present over the previous 30 days regardless of severity or whether it has improved or worsened. A SLEDAI 2K score of 3 to 4 points is representative of active disease and a decrease of 1 to 2 points is considered clinically meaningful.

  • Proportion of subjects with a ≥ 50% reduction in Cutaneous Lupus Area and Severity Index (CLASI) activity score from baseline, in subjects with Baseline CLASI activity score ≥ 10 [ Time Frame: Weeks 24 and 52 ]

    The CLASI Activity Score ranges from 0 to 70. To generate the activity score erythema is scored on a scale of 0 (absent) to 3 (dark red; purple/violaceous/crusted/hemorrhagic) and scale/hypertrophy are scored on a scale of 0 (absent) to 2 (verrucous/hypertrophic). Both the erythema and scale/hypertrophy scores are assessed in 13 different anatomical locations. In addition, the presence of mucous membrane lesions is scored on a scale of 0 (absent) to 1 (lesion or ulceration), the occurrence of recent hair loss is captured

    (1=yes; 0=no) and non-scarring alopecia is scored on a scale of 0 (absent) to 3 (focal or patchy in more than one quadrant). To calculate the activity score, all scores for erythema, scale/hypertrophy, mucous membrane lesions and alopecia are added together.


  • Proportion of subjects with no new organ system affected as defined by 1 or more BILAG A or new 2 or more BILAG B items compared to Baseline using BILAG 2004 Index [ Time Frame: Weeks 24 and 52 ]
    The BILAG 2004 is a composite index that is based on the Classic BILAG index. It is a clinical measure of lupus disease activity. This tool assesses the changing severity of clinical manifestations of SLE using an ordinal scale scoring system that contain 9 systems (constitutional, mucocutaneous, neuropsychiatric, musculoskeletal, cardiorespiratory, gastrointestinal, ophthalmic, renal and hematological). Activity in each organ system is scored as: A=most active disease; B=intermediate activity; C=mild, stable disease; D=previous involvement, currently inactive; E=no previous activity.

  • Percentage of subjects with no worsening (increase of <0.30 points from Baseline) in Physician's Global Assessment (PGA) compared to Baseline [ Time Frame: Week 24 ]
    The PGA uses a visual analog scale with scores between 0 and 3 to indicate worsening of disease. The scoring is as follows: 0 = none, 1 = mild disease, 2 = moderate disease, and 3 = severe disease.

  • Mean change from Baseline in swollen joint count in subjects with ≥ 3 swollen joints at Baseline [ Time Frame: Week 24 and 52 ]
    Joint tenderness and swelling will be noted as "present" or "absent," with no quantitation of severity using a 28- joint count.

  • Mean change from Baseline in tender joint count in subjects with ≥ 3 tender joints at Baseline [ Time Frame: Week 24 and 52 ]
    Joint tenderness will be noted as "present" or "absent," with no quantitation of severity using a 28- joint count.

  • Mean change from Baseline in PGA score [ Time Frame: Week 24 and 52 ]
    The PGA uses a visual analog scale with scores between 0 and 3 to indicate worsening of disease. The scoring is as follows: 0 = none, 1 = mild disease, 2 = moderate disease, and 3 = severe disease.

  • Change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue score [ Time Frame: Week 24 and 52 ]
    The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The total FACIT-Fatigue score ranges from 0 to 52.

  • Major clinical response defined as BILAG C or better in all organ domains at Week 24 with maintenance of this response through Week 52 [ Time Frame: Week 24 and 52 ]
    The BILAG 2004 is a composite index that is based on the Classic BILAG index. It is a clinical measure of lupus disease activity. This tool assesses the changing severity of clinical manifestations of SLE using an ordinal scale scoring system that contain 9 systems (constitutional, mucocutaneous, neuropsychiatric, musculoskeletal, cardiorespiratory, gastrointestinal, ophthalmic, renal and hematological). Activity in each organ system is scored as: A=most active disease; B=intermediate activity; C=mild, stable disease; D=previous involvement, currently inactive; E=no previous activity.

  • Corticosteroid Reduction- Week 24 [ Time Frame: Week 24 ]
    • The percentage of subjects with a prednisone or equivalent dose of ≥ 10 mg/day at Baseline whose average prednisone or equivalent dose has been reduced to ≤ 7.5 mg/day by Week 16 and maintained through Week 24 with no flares between Week 16 and Week 24
    • The percentage of subjects with a prednisone or equivalent dose of ≥ 10 mg/day at Baseline whose average prednisone or equivalent dose has been reduced to ≤ 10 mg/day by Week 16 and maintained through Week 24 with no flares between Week 16 and Week 24
    • Percent change from Baseline in OCS dose in subjects with prednisone or equivalent ≥ 10 mg/day at Baseline.
    • AUC of the total corticosteroid dose from Baseline through Week 24

  • Corticosteroid Reduction- Week 52 [ Time Frame: Week 52 ]
    • The percentage of subjects with a prednisone or equivalent dose of ≥ 10 mg/day at Baseline whose average prednisone or equivalent dose has been reduced to ≤ 7.5 mg/day by Week 40 and maintained through Week 52 with no flares between Week 40 and Week 52
    • The percentage of subjects with a prednisone or equivalent dose of ≥ 10 mg/day at Baseline whose average prednisone or equivalent dose has been reduced to ≤ 10 mg/day by Week 40 and maintained through Week 52 with no flares between Week 40 and Week 52
    • Percent change from Baseline in OCS dose in subjects with prednisone or equivalent ≥ 10 mg/day at Baseline.
    • AUC of the total corticosteroid dose from Baseline through Week 52

  • Area under the curve (AUC) of SLE flare as defined by the SLE Flare Index [ Time Frame: Up to 52 weeks ]
    The SLE Flare Index is defined by an increase in the SLEDAI of 3 or more points (mild or moderate flare) or a SLEDAI score greater than 12 (severe), a 0 to 3 visual analogue scale (VAS) with anchors for the physician global assessment (none, mild, moderate or severe flare) with an increase in 1 (for mild/moderate) or 2.5 (for severe) and adding NSAIDs or hydroxychloroquine (for mild) or steroids, but no more than 0.5 mg/kg/day and/or adding a new immunosuppressant (for severe).

  • Percentage of subjects experiencing a SLE flare as defined by the SLE Flare Index [ Time Frame: Up to 52 weeks ]
    The SLE Flare Index is defined by an increase in the SLEDAI of 3 or more points (mild or moderate flare) or a SLEDAI score greater than 12 (severe), a 0 to 3 visual analogue scale (VAS) with anchors for the physician global assessment (none, mild, moderate or severe flare) with an increase in 1 (for mild/moderate) or 2.5 (for severe) and adding NSAIDs or hydroxychloroquine (for mild) or steroids, but no more than 0.5 mg/kg/day and/or adding a new immunosuppressant (for severe).

  • : Time to flare as defined by the SLE Flare Index [ Time Frame: Up to 52 weeks ]
    The SLE Flare Index is defined by an increase in the SLEDAI of 3 or more points (mild or moderate flare) or a SLEDAI score greater than 12 (severe), a 0 to 3 visual analogue scale (VAS) with anchors for the physician global assessment (none, mild, moderate or severe flare) with an increase in 1 (for mild/moderate) or 2.5 (for severe) and adding NSAIDs or hydroxychloroquine (for mild) or steroids, but no more than 0.5 mg/kg/day and/or adding a new immunosuppressant (for severe).

  • Change from Baseline in Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index [ Time Frame: 52 weeks ]
    The SLICC/ACR Damage Index measures irreversible impairment since onset of SLE which has to be present for at least 6 months. Damage is defined for 12 separate organ systems: ocular (range 0-2), neuropsychiatric (0-6), renal (0-3), pulmonary (0-5), cardiovascular (0-6), peripheral vascular (0-5), gastrointestinal (0-6), musculoskeletal (0-7), skin (0-3), endocrine (diabetes) (0-1), gonadal (0-1) and malignancies (0-2). The maximum score for this assessment is 47 points.


Estimated Enrollment: 280
Anticipated Study Start Date: June 30, 2017
Estimated Study Completion Date: January 20, 2020
Estimated Primary Completion Date: July 22, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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)
Drug: CC-220
0.45 mg QD PO
Other: Placebo
Placebo QD PO
Experimental: 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)
Drug: CC-220
0.3 mg QD PO
Other: Placebo
Placebo QD PO
Experimental: 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)
Drug: CC-220
0.15 mg QD PO
Other: Placebo
Placebo QD PO
Placebo Comparator: Placebo
Weeks 0 to 24: CC-220 Placebo Controlled Phase: placebo once daily (QD)
Other: Placebo
Placebo QD PO

Detailed Description:

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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female 18 years of age or older at the time of signing the informed consent.
  2. Able and willing to adhere to the visit schedule and other protocol requirements.
  3. 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.
  4. 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.
  5. 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.

Exclusion Criteria:

  1. Must be off prohibited medications for a pre-specified period of time.
  2. Received intra-articular, intralesional, subcutaneous, intradermal, intramuscular or IV pulse corticosteroids 6 weeks prior to the Baseline Visit.
  3. Received an investigational product within 5 pharmacokinetic half-lives or one month, whichever is longer, prior to the Baseline Visit.
  4. 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.
  5. Proteinuria will be based upon spot urine testing.
  6. Active, severe or unstable neuropsychiatric lupus disease within 6 months of the Screening Visit.
  7. History or confirmed positive test for hepatitis B History of congenital and/or acquired mmunodeficiencies (eg, common variable immunodeficiency, human immunodeficiency virus [HIV], etc).
  8. 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.
  9. Active tuberculosis (TB) or a history of incompletely treated TB, or a positive, QuantiFERON®-TB Gold test.
  10. 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.
  11. Diagnosis of Antiphospholipid Syndrome History of arterial or venous thrombosis within one year of the Screening Visit.
  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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03161483

Contacts
Contact: Associate Director Clinical Trial Disclosure 1-888-260-1599 clinicaltrialdisclosure@celgene.com

Sponsors and Collaborators
Celgene
Investigators
Study Director: Marla Hochfeld, MD Celgene Corporation
  More Information

Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT03161483     History of Changes
Other Study ID Numbers: CC-220-SLE-002
Study First Received: May 18, 2017
Last Updated: May 23, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Celgene:
CC-220
Safety
Efficacy
Active Systemic Lupus Erythematosus

Additional relevant MeSH terms:
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on July 27, 2017