Brief Summary
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.
Brief Title
A Study of the Efficacy and Safety of MEDI-546 in Systemic Lupus Erythematosus
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Systemic Lupus Erythematosus
Eligibility 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.
* 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.
Inclusion 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.
* 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.
Gender
All
Gender Based
false
Keywords
MEDI-546
Anifrolumab
Systemic Lupus Erythematosus
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Estimated
Last Update Submit Date
Maximum Age
65 Years
Minimum Age
18 Years
NCT Id
NCT01438489
Org Class
Industry
Org Full Name
MedImmune LLC
Org Study Id
CD-IA-MEDI-546-1013
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 2, Randomized Study to Evaluate the Efficacy and Safety of MEDI-546 in Subjects With Systemic Lupus Erythematosus
Primary Outcomes
Outcome Description
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.
Outcome Measure
Percentage of Participants Achieving an Systemic Lupus Erythematosus (SLE) Responder Index [SRI (4)] Response With Oral Corticosteroids (OCS) Tapering at Day 169
Outcome Time Frame
Day 169
Outcome Description
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.
Outcome Measure
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
Outcome Time Frame
Day 169
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
Day 365
Outcome Measure
Percentage of Participants Achieving an Systemic Lupus Erythematosus (SLE) Responder Index [SRI (4)] Response With Oral Corticosteroids (OCS) Tapering at Day 365
Outcome Description
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.
Outcome Time Frame
Day 365
Outcome Measure
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
Outcome Description
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.
Outcome Time Frame
Day 1 (Baseline) to Day 422 (End of Study)
Outcome Measure
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESIs) and Treatment-Emergent Serious Adverse Events (TESAEs)
Outcome Description
Any medically significant change in laboratory evaluations were recorded as Treatment emergent adverse events.
Outcome Time Frame
Day 1 (Baseline) to Day 422 (End of Study)
Outcome Measure
Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events
Outcome Description
Vital sign parameters are temperature, blood pressure, respiratory rate, heart rate and weight. Vital signs abnormalities were reported as TEAEs.
Outcome Time Frame
Day 1 (Baseline) to Day 422 (End of Study)
Outcome Measure
Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs)
Outcome Description
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.
Outcome Time Frame
Day 1 (Baseline) to Day 422 (End of Study)
Outcome Measure
Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs)
Outcome Description
Anti-drug antibody responses to anifrolumab in serum were evaluated.
Outcome Time Frame
Days 1, 85, 141, 169, 253, 337 (Treatment Phase), 365, 396, and 422 (Follow-up Period)
Outcome Measure
Percentage of SLE Participants With Positive Anti-drug Antibody (ADA)
Outcome Description
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.
Outcome Time Frame
Days 29, 85, 141, 169, 253, 337 (treatment phase), on Days 365, 396, and 422 (follow up period)
Outcome Measure
Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature
Outcome Description
Maximum plasma concentration (Cmax) was defined as the peak plasma level of anifrolumab, derived from plasma concentration -time data.
Outcome Time Frame
Pre-infusion and 15 minutes post-infusion on Day 1, 169 and 337
Outcome Measure
Maximum Observed Plasma Concentration (Cmax) of Anifrolumab at Day 1, 169 and 337
Outcome Description
Accumulation ratio for maximum plasma concentration (Cmax,AR) of anifrolumab after multiple administration at Day 169 and 337 was calculated.
Outcome Time Frame
Pre-infusion and 15 minutes post-infusion on Day 169 and 337
Outcome Measure
Accumulation Ratio of Maximum Observed Plasma Concentration (Cmax,AR) of Anifrolumab
Outcome Description
Trough concentration (Ctrough) of anifrolumab at Day 29, 169 and 365 were calculated.
Outcome Time Frame
Pre-infusion and 15 minutes post-infusion on Day 29, 169 and 365
Outcome Measure
Trough Concentration (Ctrough) of Anifrolumab at Day 29, 169 and 365
Outcome Description
Accumulation ratio for trough concentration (Ctrough,AR) of anifrolumab after multiple administration at Day 169 and 365 was calculated.
Outcome Time Frame
Pre-infusion and 15 minutes post-infusion on Day 169 and 365
Outcome Measure
Accumulation Ratio of Trough Concentration (Ctrough,AR) of Anifrolumab at Day 169 and 365
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
65
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Chaim Putterman
Investigator Email
chaim.putterman@einsteinmed.org
Investigator Phone
718-430-4266