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

• ClinicalTrials.gov Identifier: NCT01283139
• Recruitment Status: Completed
• First Posted: January 25, 2011
• Results First Posted: July 11, 2016
• Last Update Posted: April 19, 2018
• Sponsor: MedImmune LLC
• Information provided by (Responsible Party): MedImmune LLC

Tracking Information

• First Submitted Date: January 20, 2011
• First Posted Date: January 25, 2011
• Results First Submitted Date: June 1, 2016
• Results First Posted Date: July 11, 2016
• Last Update Posted Date: April 19, 2018
• Actual Study Start Date: March 31, 2011
• Actual Primary Completion Date: November 14, 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 1, 2016)

• Percentage of Participants Achieving a Response in Systemic Lupus Erythematosus Responder Index 4 (SRI [4]) [ Time Frame: Day 365 ]
  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 ]
  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).

• Original Primary Outcome Measures (submitted: January 24, 2011): Proportion of subjects achieving a response in an SLE responder index at Day 365 [ Time Frame: Day 365 ]

Current Secondary Outcome Measures (submitted: June 1, 2016)

• 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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Efficacy and Safety of Sifalimumab in Adults With Systemic Lupus Erythematosus
• Official Title: A Phase 2b, Dose-ranging Study to Evaluate the Efficacy and Safety of Sifalimumab in Adults With Systemic Lupus Erythematosus
• Brief Summary: To evaluate the efficacy and safety of sifalimumab compared to placebo in subjects with moderately to severely active Systemic Lupus Erythematosus (SLE).
• 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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Systemic Lupus Erythematosus

Intervention

• 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
• 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
• 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
• Other: Placebo
  IV Placebo every 2 weeks for 4 weeks and then monthly for 44 weeks

Study Arms

• 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.
  Intervention: Biological: Sifalimumab 200 mg
• 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.
  Intervention: Biological: Sifalimumab 600 mg
• 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.
  Intervention: Biological: Sifalimumab 1,200 mg
• 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.
  Intervention: Other: Placebo

Publications *

• Khamashta M, Merrill JT, Werth VP, Furie R, Kalunian K, Illei GG, Drappa J, Wang L, Greth W; CD1067 study investigators. Sifalimumab, an anti-interferon-alpha monoclonal antibody, in moderate to severe systemic lupus erythematosus: a randomised, double-blind, placebo-controlled study. Ann Rheum Dis. 2016 Nov;75(11):1909-1916. doi: 10.1136/annrheumdis-2015-208562. Epub 2016 Mar 23.
• 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.
• Brohawn PZ, Streicher K, Higgs BW, Morehouse C, Liu H, Illei G, Ranade K. Type I interferon gene signature test-low and -high patients with systemic lupus erythematosus have distinct gene expression signatures. Lupus. 2019 Nov;28(13):1524-1533. doi: 10.1177/0961203319885447. Epub 2019 Oct 29.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 11, 2016): 834
• Original Estimated Enrollment (submitted: January 24, 2011): 544
• Actual Study Completion Date: April 17, 2014
• Actual Primary Completion Date: November 14, 2013 (Final data collection date for primary outcome measure)
• Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Brazil, Bulgaria, Canada, Chile, France, Germany, Hungary, India, Italy, Jamaica, Mexico, Netherlands, Peru, Philippines, Poland, Romania, South Africa, Spain, Thailand, United Kingdom, United States

Administrative Information

• NCT Number: NCT01283139
• Other Study ID Numbers: CD-IA-MEDI-545-1067; 2010-024069-30 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: MedImmune LLC
• Original Responsible Party: Warren Greth, MD, MedImmune LLC
• Current Study Sponsor: MedImmune LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Gabor Illei, MD; MedImmune LLC

• PRS Account: MedImmune LLC
• Verification Date: March 2018