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A Study to Evaluate the Efficacy and Safety of Sifalimumab in Adults With Systemic Lupus Erythematosus

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT01283139
First received: January 20, 2011
Last updated: July 11, 2016
Last verified: July 2016
  Purpose
To evaluate the efficacy and safety of sifalimumab compared to placebo in subjects with moderately to severely active Systemic Lupus Erythematosus (SLE).

Condition Intervention Phase
Systemic Lupus Erythematosus
Biological: Sifalimumab 200 mg
Biological: Sifalimumab 600 mg
Biological: Sifalimumab 1,200 mg
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2b, Dose-ranging Study to Evaluate the Efficacy and Safety of Sifalimumab in Adults With Systemic Lupus Erythematosus

Resource links provided by NLM:


Further study details as provided by MedImmune LLC:

Primary Outcome Measures:
  • Percentage of Participants Achieving a Response in Systemic Lupus Erythematosus Responder Index 4 (SRI [4]) [ Time Frame: Day 365 ] [ Designated as safety issue: No ]
    SRI (4) responder is defined as: 1) a reduction in baseline Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) disease activity score of greater than or equal to (>=) 4 points (with increased deoxyribonucleic acid [DNA] binding item of SLEDAI-2K score based on the ANA Multi−Lyte® ANA−II Plus Test System); 2) no worsening in Physician Global Assessment (MDGA) (worsening is defined as an increase of >=0.3 from baseline on a 0-3 visual analogue scale) and 3) no worsening in British Isles Lupus Assessment Group (BILAG-2004) (worsening is defined as at least 1 new 'A' score or 2 new 'B' scores on the BILAG-2004 compared with baseline).

  • Percentage of Participants Achieving a Positive Response in SRI (4) in 4-Gene Interferon Test High Participants [ Time Frame: Day 365 ] [ Designated as safety issue: No ]
    SRI (4) responder is defined as: 1) a reduction in baseline SLEDAI-2K disease activity score of >=4 points (with increased DNA binding item of SLEDAI-2K score based on the ANA Multi−Lyte® ANA−II Plus Test System); 2) no worsening in Physician Global Assessment (MDGA) (worsening is defined as an increase of >=0.3 from baseline on a 0-3 visual analogue scale) and 3) no worsening in BILAG-2004 (worsening is defined as at least 1 new 'A' score or 2 new 'B' scores on the BILAG-2004 compared with baseline).


Secondary Outcome Measures:
  • Percentage of Participants on Greater Than or Equal to 10 mg/Day Oral Prednisone (or Equivalent) at Baseline Who Were Able to Reduce to Less Than or Equal to (<=) 7.5 mg/Day [ Time Frame: Day 365 ] [ Designated as safety issue: No ]
    Percentage of participants on >=10 mg/day oral corticosteroids (OCS) at baseline who were able to taper it to <=7.5 mg/day by Day 365 were recorded.

  • Percentage of Participants With a Cutaneous Lupus Erythematosus Disease Activity and Severity Index (CLASI) Activity Score Greater Than or Equal to (>=) 10 at Baseline Who Achieved a >= 4-point Reduction [ Time Frame: Day 365 ] [ Designated as safety issue: No ]
    The CLASI consists of two scores, the first summarizes the activity of the disease while the second is a measure of the damage done by the disease. Activity is scored on the basis of erythema, scale/hyperkeratosis, mucous membrane involvement, acute hair loss and non-scarring alopecia. Damage is scored in terms of dyspigmentation and scarring, including scarring alopecia. The percentage of participants with a CLASI activity score >=10 at baseline who achieved a clinically significant (>=4-point) reduction at Day 365 were reported.

  • Percentage of Participants Who Achieved a Greater Than 3-Point Improvement in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale [ Time Frame: Day 365 ] [ Designated as safety issue: No ]
    FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (not at all) to 4 (very much). Larger the participant's response to the questions (with the exception of 2 negatively stated), greater was the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score).

  • Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs) [ Time Frame: Day 1 up to Week 74 ] [ Designated as safety issue: Yes ]
    An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent defined as events present at baseline that worsened in intensity after administration of investigational product or events absent at baseline that emerged after administration of investigational product, for the period extending until the end of participant participation in the study.

  • Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Day 1 up to Week 61 ] [ Designated as safety issue: Yes ]
    Laboratory investigations included hematology, serum chemistries and urinalysis parameters. Participants with clinically significant abnormalities in these laboratory investigations recorded as TEAEs were reported.

  • Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Day 1 up to Week 61 ] [ Designated as safety issue: Yes ]
    Vital sign assessments included blood pressure, pulse rate, temperature, weight and respiratory rate. Vital signs abnormalities recorded as TEAEs were reported.

  • Number of Participants With Abnormal Electrocardiogram (ECG) Findings Reported as TEAEs [ Time Frame: Day 1 up to Week 56 ] [ Designated as safety issue: Yes ]
    The 12-lead ECG data were summarized and evaluated. Number of participants with clinically significant abnormal ECG findings as assessed by cardiologist were recorded and reported as TEAEs.


Enrollment: 834
Study Start Date: March 2011
Study Completion Date: April 2014
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sifalimumab 200 milligram (mg)
Sifalimumab 200 milligram (mg) will be administered intravenously every 2 weeks for 4 weeks and then monthly for 44 weeks for a total of 14 doses.
Biological: Sifalimumab 200 mg
Sifalimumab 200 mg intravenously every 2 weeks for 4 weeks and then monthly for 44 weeks for a total of 14 doses.
Other Name: MEDI-545
Experimental: Sifalimumab 600 mg
Sifalimumab 600 mg will be administered intravenously every 2 weeks for 4 weeks and then monthly for 44 weeks for a total of 14 doses.
Biological: Sifalimumab 600 mg
Sifalimumab 600 mg intravenously every 2 weeks for 4 weeks and then monthly for 44 weeks for a total of 14 doses.
Other Name: MEDI-545
Experimental: Sifalimumab 1,200 mg
Sifalimumab 1,200 mg will be administered intravenously every 2 weeks for 4 weeks and then monthly for 44 weeks for a total of 14 doses.
Biological: Sifalimumab 1,200 mg
Sifalimumab 1,200 mg intravenously every 2 weeks for 4 weeks and then monthly for 44 weeks for a total of 14 doses.
Other Name: MEDI-545
Placebo Comparator: Placebo
Placebo matching to sifalimumab will be administered intravenously at a fixed dose every 2 weeks for 4 weeks and then monthly for 44 weeks for a total of 14 doses.
Other: Placebo
IV Placebo every 2 weeks for 4 weeks and then monthly for 44 weeks

Detailed Description:
This is a Phase 2b, multinational, multicenter, randomized, double-blind, placebo controlled, parallel group study to evaluate the efficacy and safety of three intravenous (IV) treatment regimens of sifalimumab (200, 600, or 1,200 mg) in adult subjects with chronic moderately-to-severely active SLE with an inadequate response to standard of care (SOC) for SLE.
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
Inclusion Criteria: - Fulfills at least 4 of American College of Rheumatology (ACR) criteria for systemic lupus erythematosus (SLE) including a positive antinuclear antibody (ANA) or elevated ds-deoxyribonucleic acid (DNA) or Sm antibody at screening - Disease history of SLE greater than or equal to (>=) 24 weeks at screening - Weight more than (>) 40 kilogram (kg) - Currently receiving stable dose of oral prednisone and/or antimalarials/immunosuppressives - Active moderate to severe SLE disease based on SLE disease activity score (SLEDAI) and British Isles Lupus Assessment Group Index (BILAG) and Physicians Global Assessment - No evidence of cervical malignancy on PAP within 6 months of randomization - Female subjects must be willing to avoid pregnancy - Negative TB test or newly positive TB test due to latent TB for which treatment must be initiated at or before randomization. Exclusion Criteria: - Active severe SLE-driven renal disease or unstable renal disease prior to screening - Active severe or unstable neuropsychiatric SLE - Clinically significant active infection including ongoing and chronic infections - History of human immunodeficiency virus (HIV) - Confirmed Positive tests for Hepatitis B or positive test for hepatitis C - History of severe herpes infection such as herpes encephalitis, ophthalmic herpes, disseminated herpes - Herpes Zoster within 3 months of screening - History of cancer other than basal cancer or cervical cancer treated with apparent success >=1 year prior to randomization - Receipt of a biologic agent within 5 half-lives or prior to loss of pharmacodynamic and/or clinical effect (whichever is longer) prior to screening - Live or attenuated vaccine within 4 weeks prior to screening - Subjects with substance abuse - Subjects with significant hematologic abnormalities.
  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: NCT01283139

  Show 110 Study Locations
Sponsors and Collaborators
MedImmune LLC
Investigators
Study Director: Gabor Illei, MD MedImmune LLC
  More Information

Additional Information:
Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT01283139     History of Changes
Other Study ID Numbers: CD-IA-MEDI-545-1067  2010-024069-30 
Study First Received: January 20, 2011
Results First Received: June 1, 2016
Last Updated: July 11, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by MedImmune LLC:
SLE
Systemic Lupus Erythematosus
Sifalimumab
MEDI-545

Additional relevant MeSH terms:
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 27, 2016