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A Study of the Efficacy and Safety of MEDI-546 in Systemic Lupus Erythematosus

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT01438489
First received: September 9, 2011
Last updated: July 5, 2016
Last verified: July 2016
  Purpose
The purpose of this study is to evaluate the efficacy and safety of MEDI-546 compared to placebo in subjects with chronic, moderately-to-severely active systemic lupus erythematosus (SLE) with an inadequate response to standard of care treatment for SLE.

Condition Intervention Phase
Systemic Lupus Erythematosus
Biological: Anifrolumab 300 mg
Biological: Anifrolumab 1000 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, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2, Randomized Study to Evaluate the Efficacy and Safety of MEDI-546 in Subjects With Systemic Lupus Erythematosus

Resource links provided by NLM:


Further study details as provided by MedImmune LLC:

Primary Outcome Measures:
  • Percentage of Participants Achieving an Systemic Lupus Erythematosus (SLE) Responder Index [SRI (4)] Response With Oral Corticosteroids (OCS) Tapering at Day 169 [ Time Frame: Day 169 ] [ Designated as safety issue: No ]
    An SRI (4) responder defined as a participant who had 1) a reduction in baseline Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of greater than or equal to (>=) 4 points; 2) no worsening of disease from baseline as measured by the Physician Global Assessment (MDGA) (worsening was defined as an increase of >= 0.3 from baseline on a 0 to 3.0 visual analog scale); and 3) no new British Isles Lupus Assessment Group 2004 (BILAG-2004) Index 'A' organ system score and no more than one new or worsening BILAG-2004 Index 'B' organ system score. OCS tapering requires a sustained reduction of OCS from Day 85 through Day 169 [less than 10 milligram per day (mg/day) and less or equal to the dose received on Day 1]. SRI was analyzed by a logistic regression model.

  • Percentage of Type I Interferon (IFN) Test High Participants Achieving an Systemic Lupus Erythematosus Responder Index (SRI) (4) Response With Oral Corticosteroids (OCS) Tapering at Day 169 [ Time Frame: Day 169 ] [ Designated as safety issue: No ]
    Type I IFN signature in whole blood assessed by using a 4-gene diagnostic test. The blood samples collected were to be used to prospectively identify participants as IFN test-high or test-low. The results of this test were used to stratify participants. An SRI (4) Responder was defined as a participant who had 1) a reduction in baseline SLEDAI-2K disease activity score of >= 4 points; 2) no worsening of disease from baseline as measured by the Physician Global Assessment (MDGA) (worsening was defined as an increase of >= 0.3 from baseline on a 0 to 3.0 visual analog scale); and 3) no new British Isles Lupus Assessment Group 2004 (BILAG-2004) Index A organ system score and no more than one new or worsening BILAG-2004 Index B organ system score. OCS tapering requires a sustained reduction of OCS from Day 85 through Day 169 [less than 10 mg/day and less or equal to the dose received on Day 1]. SRI was analyzed by a logistic regression model.


Secondary Outcome Measures:
  • Percentage of Participants Achieving an Systemic Lupus Erythematosus (SLE) Responder Index [SRI (4)] Response With Oral Corticosteroids (OCS) Tapering at Day 365 [ Time Frame: Day 365 ] [ Designated as safety issue: No ]
    An SRI (4) Responder was defined as a participant who had 1) a reduction in baseline SLEDAI-2K disease activity score of >= 4 points; 2) no worsening of disease from baseline as measured by the MDGA (worsening was defined as an increase of >= 0.3 from baseline on a 0 to 3.0 visual analog scale); and 3) no new British Isles Lupus Assessment Group 2004 (BILAG-2004) Index A organ system score and no more than one new or worsening BILAG-2004 Index B organ system score. OCS tapering requires a sustained reduction of OCS from Day 281 through Day 365 (less than 10 mg/day and less or equal to the dose received on Day 1). SRI was analyzed by a logistic regression model.

  • Percentage of Participants on Oral Corticosteroids (OCS) >=10 mg/Day of Prednisone or Equivalent at Baseline Who Were Able to Taper to Less Than or Equal to (<=) 7.5 mg/Day at Day 365 [ Time Frame: Day 365 ] [ Designated as safety issue: No ]
    Participants on OCS >=10 mg/day of prednisone or equivalent at baseline who were able to taper to <= 7.5 mg/day at Day 365 were evaluated.

  • Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESIs) and Treatment-Emergent Serious Adverse Events (TESAEs) [ Time Frame: Day 1 (Baseline) to Day 422 (End of Study) ] [ Designated as safety issue: Yes ]
    An adverse event (AE) was any untoward medical occurrence in a study participant administered a pharmaceutical product and which does not necessarily have a causal relationship with treatment. A serious AE (SAE) was an AE resulting in any of following outcomes or deemed significant for any other reason: death; initial/prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly (in offspring of participant). AEs may be treatment emergent (TE) [that is, occurring after initial receipt of investigational product] or non-TE. An AESI is one of scientific and medical concern specific to understanding biologics and requires close monitoring and rapid communication by investigator to sponsor.

  • Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events [ Time Frame: Day 1 (Baseline) to Day 422 (End of Study) ] [ Designated as safety issue: Yes ]
    Any medically significant change in laboratory evaluations were recorded as Treatment emergent adverse events.

  • Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Day 1 (Baseline) to Day 422 (End of Study) ] [ Designated as safety issue: Yes ]
    Vital sign parameters are temperature, blood pressure, respiratory rate, heart rate and weight. Vital signs abnormalities were reported as TEAEs.

  • Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Day 1 (Baseline) to Day 422 (End of Study) ] [ Designated as safety issue: Yes ]
    Any medically significant changes from the screening ECG was recorded as TEAEs. An abnormal ECG findings such as QT prolonged were reported as treatment emergent adverse events.

  • Percentage of SLE Participants With Positive Anti-drug Antibody (ADA) [ Time Frame: Days 1, 85, 141, 169, 253, 337 (Treatment Phase), 365, 396, and 422 (Follow-up Period) ] [ Designated as safety issue: No ]
    Anti-drug antibody responses to anifrolumab in serum were evaluated.

  • Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature [ Time Frame: Days 29, 85, 141, 169, 253, 337 (treatment phase), on Days 365, 396, and 422 (follow up period) ] [ Designated as safety issue: No ]
    The PD positive and negative gene signature was determined by comparing the expression of type I IFN-inducible genes in a 21-gene panel in study participants relative to pooled normal blood collected from healthy participants.

  • Maximum Observed Plasma Concentration (Cmax) of Anifrolumab at Day 1, 169 and 337 [ Time Frame: Day 1, 169 and 337 ] [ Designated as safety issue: No ]
    Maximum plasma concentration (Cmax) was defined as the peak plasma level of anifrolumab, derived from plasma concentration -time data.

  • Accumulation Ratio of Maximum Observed Plasma Concentration (Cmax,AR) of Anifrolumab [ Time Frame: Day 169 and 337 ] [ Designated as safety issue: No ]
    Accumulation ratio for maximum plasma concentration (Cmax,AR) of anifrolumab after multiple administration at Day 169 and 337 was calculated.

  • Trough Concentration (Ctrough) of Anifrolumab at Day 29, 169 and 365 [ Time Frame: Day 29, 169 and 365 ] [ Designated as safety issue: No ]
    Trough concentration (Ctrough) of anifrolumab at Day 29, 169 and 365 were calculated.

  • Accumulation Ratio of Trough Concentration (Ctrough,AR) of Anifrolumab at Day 169 and 365 [ Time Frame: Day 169 and 365 ] [ Designated as safety issue: No ]
    Accumulation ratio for trough concentration (Ctrough,AR) of anifrolumab after multiple administration at Day 169 and 365 was calculated.


Enrollment: 626
Study Start Date: January 2012
Study Completion Date: April 2015
Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Anifrolumab (MEDI-546) 300 mg
Participants will receive 300 milligram (mg) anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
Biological: Anifrolumab 300 mg
Participants will receive 300 milligram (mg) anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
Other Name: MEDI-546
Experimental: Anifrolumab (MEDI-546) 1000 mg
Participants will receive 1000 mg anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
Biological: Anifrolumab 1000 mg
Participants will receive 1000 mg anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
Other Name: MEDI-546
Placebo Comparator: Matching Placebo
Participants will receive placebo matched to anifrolumab intravenous (IV) infusion every 4 weeks for 48 weeks.
Other: Placebo
Participants will receive placebo matched to anifrolumab intravenous (IV) infusion every 4 weeks for 48 weeks.

Detailed Description:
This is a Phase 2, multinational, multicenter, randomized, double-blind, placebo controlled, parallel-group study to evaluate the efficacy and safety of 2 intravenous (IV) treatment regimens in adult participants with chronic, moderately-to-severely active SLE with an inadequate response to SOC SLE. The investigational product (anifrolumab or placebo) will be administered as a fixed dose every 4 weeks (28 days) for a total of 13 doses.
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Fulfills at least 4 of the 11 American College of Rheumatology (ACR) criteria for systemic lupus erythematosus (SLE) including a positive antinuclear antibody (ANA) greater than or equal to 1:80 or elevated anti-double-stranded DNA or anti-Smith antibody at screening
  • Pediatric or adult SLE with chronic disease activity for greater than or equal to 24 weeks
  • Weight greater than or equal to 40 kg
  • Currently receiving stable dose of oral prednisone (or equivalent) less than or equal to 40 mg/day 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 smear within 2 years of randomization
  • Female participants must be willing to avoid pregnancy
  • Negative tuberculosis (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
  • Live or attenuated vaccine within 4 weeks prior to screening
  • Participants 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: NCT01438489

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Sponsors and Collaborators
MedImmune LLC
Investigators
Study Director: Warren Greth, MD MedImmune LLC
  More Information

Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT01438489     History of Changes
Other Study ID Numbers: CD-IA-MEDI-546-1013 
Study First Received: September 9, 2011
Results First Received: July 5, 2016
Last Updated: July 5, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by MedImmune LLC:
MEDI-546
Anifrolumab
Systemic Lupus Erythematosus

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 28, 2016