Phase 2
N=307
A Study of the Efficacy and Safety of MEDI-546 in Systemic Lupus Erythematosus
Systemic Lupus Erythematosus
Bottom Line
View on ClinicalTrials.gov: NCT01438489 ↗Enrolled (actual)
307
Serious AEs
17.4%
Results posted
Aug 2016
Primary outcome: Primary: Percentage of Participants Achieving an Systemic Lupus Erythematosus (SLE) Responder Index [SRI (4)] Response With Oral Corticosteroids (OCS) Tapering at Day 169 — 17.6; 34.3; 28.8 Percentage of Participants — p=0.014
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Anifrolumab 300 mg (Biological); Anifrolumab 1000 mg (Biological); Placebo (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- MedImmune LLC
- Primary completion
- Apr 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Achieving an Systemic Lupus Erythematosus (SLE) Responder Index [SRI (4)] Response With Oral Corticosteroids (OCS) Tapering at Day 169 |
17.6; 34.3; 28.8 | 0.014 sig |
| PRIMARY 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 |
13.2; 36; 28.2 | 0.004 sig |
| SECONDARY Percentage of Participants Achieving an Systemic Lupus Erythematosus (SLE) Responder Index [SRI (4)] Response With Oral Corticosteroids (OCS) Tapering at Day 365 |
25.5; 51.5; 38.5 | — |
| SECONDARY 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 |
26.6; 56.4; 31.7 | — |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESIs) and Treatment-Emergent Serious Adverse Events (TESAEs) |
78; 84; 90; 19; 16; 18 | — |
| SECONDARY Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events |
0; 1; 3; 0; 1; 2 | — |
| SECONDARY Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) |
7; 3; 2; 5; 0; 3 | — |
| SECONDARY Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) |
0; 0; 2 | — |
| SECONDARY Percentage of SLE Participants With Positive Anti-drug Antibody (ADA) |
1.0; 1.0; 1.9; 1.1; 0.0; 0.0 | — |
| SECONDARY Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature |
-0.753; 70.194; 82.056; -5.412; 72.639; 79.350 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) of Anifrolumab at Day 1, 169 and 337 |
82.8; 248; 110; 375; 127; 439 | — |
| SECONDARY Accumulation Ratio of Maximum Observed Plasma Concentration (Cmax,AR) of Anifrolumab |
1.36; 1.43; 1.56; 1.76 | — |
| SECONDARY Trough Concentration (Ctrough) of Anifrolumab at Day 29, 169 and 365 |
7.95; 46.8; 18.4; 110; 23.6; 154 | — |
| SECONDARY Accumulation Ratio of Trough Concentration (Ctrough,AR) of Anifrolumab at Day 169 and 365 |
2.49; 2.29; 3.06; 3.02 | — |
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.
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.
Data sourced from ClinicalTrials.gov (NCT01438489). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.