Clinical trial NCT01438489: A Study of the Efficacy and Safety of MEDI-546 in Systemic Lupus Erythematosus
Official title: A Phase 2, Randomized Study to Evaluate the Efficacy and Safety of MEDI-546 in Subjects With Systemic Lupus Erythematosus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Systemic Lupus Erythematosus
Keywords: MEDI-546
Anifrolumab
Systemic Lupus Erythematosus
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2011-09-22
Enrollment: 626
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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.

Primary outcomes:
measure: Percentage of Participants Achieving an Systemic Lupus Erythematosus (SLE) Responder Index [SRI (4)] Response With Oral Corticosteroids (OCS) Tapering at Day 169
timeFrame: Day 169
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
timeFrame: Day 169
Secondary outcomes:
measure: Percentage of Participants Achieving an Systemic Lupus Erythematosus (SLE) Responder Index [SRI (4)] Response With Oral Corticosteroids (OCS) Tapering at Day 365
timeFrame: Day 365
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
timeFrame: Day 365
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESIs) and Treatment-Emergent Serious Adverse Events (TESAEs)
timeFrame: Day 1 (Baseline) to Day 422 (End of Study)
measure: Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events
timeFrame: Day 1 (Baseline) to Day 422 (End of Study)
measure: Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Day 1 (Baseline) to Day 422 (End of Study)
measure: Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Day 1 (Baseline) to Day 422 (End of Study)
measure: Percentage of SLE Participants With Positive Anti-drug Antibody (ADA)
timeFrame: Days 1, 85, 141, 169, 253, 337 (Treatment Phase), 365, 396, and 422 (Follow-up Period)
measure: Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature
timeFrame: Days 29, 85, 141, 169, 253, 337 (treatment phase), on Days 365, 396, and 422 (follow up period)
measure: Maximum Observed Plasma Concentration (Cmax) of Anifrolumab at Day 1, 169 and 337
timeFrame: Pre-infusion and 15 minutes post-infusion on Day 1, 169 and 337
measure: Accumulation Ratio of Maximum Observed Plasma Concentration (Cmax,AR) of Anifrolumab
timeFrame: Pre-infusion and 15 minutes post-infusion on Day 169 and 337
measure: Trough Concentration (Ctrough) of Anifrolumab at Day 29, 169 and 365
timeFrame: Pre-infusion and 15 minutes post-infusion on Day 29, 169 and 365
measure: Accumulation Ratio of Trough Concentration (Ctrough,AR) of Anifrolumab at Day 169 and 365
timeFrame: Pre-infusion and 15 minutes post-infusion on Day 169 and 365
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: La Jolla
country: United States
facility: Research Site
state: California
city: La Palma
country: United States
facility: Research Site
state: California
city: Long Beach
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Palm Desert
country: United States
facility: Research Site
state: California
city: San Leandro
country: United States
facility: Research Site
state: California
city: Upland
country: United States
facility: Research Site
state: California
city: Miami
country: United States
facility: Research Site
state: Florida
city: Ocala
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Palm Harbor
country: United States
facility: Research Site
state: Florida
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Decatur
country: United States
facility: Research Site
state: Georgia
city: Stockbridge
country: United States
facility: Research Site
state: Georgia
city: Idaho Falls
country: United States
facility: Research Site
state: Idaho
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Indianapolis
country: United States
facility: Research Site
state: Indiana
city: Las Cruces
country: United States
facility: Research Site
state: New Mexico
city: New York
country: United States
facility: Research Site
state: New York
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Raleigh
country: United States
facility: Research Site
state: North Carolina
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Edmond
country: United States
facility: Research Site
state: Oklahoma
city: Tulsa
country: United States
facility: Research Site
state: Oklahoma
city: Memphis
country: United States
facility: Research Site
state: Tennessee
city: Houston
country: United States
facility: Research Site
state: Texas
city: Seattle
country: United States
facility: Research Site
state: Washington
city: Spokane
country: United States
facility: Research Site
state: Washington
city: Rio de Janeiro
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: Plovdiv
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Barranquilla
country: Colombia
facility: Research Site
city: Bogota
country: Colombia
facility: Research Site
city: Bucaramanga
country: Colombia
facility: Research Site
city: Chia
country: Colombia
facility: Research Site
city: Medellin
country: Colombia
facility: Research Site
city: Brno
country: Czech Republic
facility: Research Site
city: Praha 2
country: Czech Republic
facility: Research Site
city: Uherske Hradiste
country: Czech Republic
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Debrecen
country: Hungary
facility: Research Site
city: Dantoli-Nagpur
country: India
facility: Research Site
city: Hyderabad
country: India
facility: Research Site
city: Mumbai
country: India
facility: Research Site
city: New Delhi
country: India
facility: Research Site
city: Pune
country: India
facility: Research Site
city: Secunderabad
country: India
facility: Research Site
city: Gwangjin-gu
country: Korea, Republic of
facility: Research Site
city: Gwangju
country: Korea, Republic of
facility: Research Site
city: Seodaemun-gu
country: Korea, Republic of
facility: Research Site
city: Suwon-si
country: Korea, Republic of
facility: Research Site
city: Guadalajara
country: Mexico
facility: Research Site
city: Leon
country: Mexico
facility: Research Site
city: Mexico
country: Mexico
facility: Research Site
city: Toluca
country: Mexico
facility: Research Site
city: Arequipa
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Bialystok
country: Poland
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Krakow
country: Poland
facility: Research Site
city: Nadarzyn
country: Poland
facility: Research Site
city: Poznan
country: Poland
facility: Research Site
city: Brasov
country: Romania
facility: Research Site
city: Iasi
country: Romania
facility: Research Site
city: Targu Mures
country: Romania
facility: Research Site
city: Chiayi
country: Taiwan
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Donetsk
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Lugansk
country: Ukraine
facility: Research Site
city: Lviv
country: Ukraine
facility: Research Site
city: Ternopil
country: Ukraine
facility: Research Site
city: Vinnitsya
country: Ukraine
facility: Research Site
city: Vinnytsia
country: Ukraine
facility: Research Site
Study officials:
affiliation: MedImmune LLC
name: Warren Greth, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Casey KA, Smith MA, Sinibaldi D, Seto NL, Playford MP, Wang X, Carlucci PM, Wang L, Illei G, Yu B, Wang S, Remaley AT, Mehta NN, Kaplan MJ, White WI. Modulation of Cardiometabolic Disease Markers by Type I Interferon Inhibition in Systemic Lupus Erythematosus. Arthritis Rheumatol. 2021 Mar;73(3):459-471. doi: 10.1002/art.41518. Epub 2021 Feb 15.
citation: 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.
citation: Casey KA, Guo X, Smith MA, Wang S, Sinibaldi D, Sanjuan MA, Wang L, Illei GG, White WI. Type I interferon receptor blockade with anifrolumab corrects innate and adaptive immune perturbations of SLE. Lupus Sci Med. 2018 Nov 22;5(1):e000286. doi: 10.1136/lupus-2018-000286. eCollection 2018.
citation: Furie R, Khamashta M, Merrill JT, Werth VP, Kalunian K, Brohawn P, Illei GG, Drappa J, Wang L, Yoo S; CD1013 Study Investigators. Anifrolumab, an Anti-Interferon-alpha Receptor Monoclonal Antibody, in Moderate-to-Severe Systemic Lupus Erythematosus. Arthritis Rheumatol. 2017 Feb;69(2):376-386. doi: 10.1002/art.39962.