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

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

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 Erythemato

Brief Summary:

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.

Detailed Summary:

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.

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

Original Primary Outcome: Same as current

Current Secondary Outcome:

• 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 [ 
  
  

  Original Secondary Outcome: Same as current
  
  Information By: Celgene
  

  Dates:
  Date Received: May 18, 2017
  Date Started: June 30, 2017
  Date Completion: January 20, 2020
  Last Updated: May 18, 2017
  Last Verified: May 2017