Clinical trial NCT01283139: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Systemic Lupus Erythematosus
Keywords: SLE
Systemic Lupus Erythematosus
Sifalimumab
MEDI-545
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2011-01-25
Enrollment: 834
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Percentage of Participants Achieving a Response in Systemic Lupus Erythematosus Responder Index 4 (SRI [4])
timeFrame: Day 365
measure: Percentage of Participants Achieving a Positive Response in SRI (4) in 4-Gene Interferon Test High Participants
timeFrame: Day 365
Secondary outcomes:
measure: 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
timeFrame: Day 365
measure: 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
timeFrame: Day 365
measure: Percentage of Participants Who Achieved a Greater Than 3-Point Improvement in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale
timeFrame: Day 365
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs)
timeFrame: Day 1 up to Week 74
measure: Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Day 1 up to Week 61
measure: Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Day 1 up to Week 61
measure: Number of Participants With Abnormal Electrocardiogram (ECG) Findings Reported as TEAEs
timeFrame: Day 1 up to Week 56
Other outcomes:
Locations:
city: La Jolla
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: Fort Lauderdale
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Stockbridge
country: United States
facility: Research Site
state: Georgia
city: Idaho Falls
country: United States
facility: Research Site
state: Idaho
city: Shreveport
country: United States
facility: Research Site
state: Louisiana
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Lansing
country: United States
facility: Research Site
state: Michigan
city: Brooklyn
country: United States
facility: Research Site
state: New York
city: Manhasset
country: United States
facility: Research Site
state: New York
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: Dallas
country: United States
facility: Research Site
state: Texas
city: Seattle
country: United States
facility: Research Site
state: Washington
city: Buenos Aires
country: Argentina
facility: Research Site
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Research Site
city: Ciudad de Buenos Aires
country: Argentina
facility: Research Site
city: La Plata
country: Argentina
facility: Research Site
city: Quilmes
country: Argentina
facility: Research Site
city: San Miguel de Tucuman
country: Argentina
facility: Research Site
city: Tucuman
country: Argentina
facility: Research Site
city: Curitiba
country: Brazil
facility: Research Site
city: Goiania
country: Brazil
facility: Research Site
city: Juiz de Fora
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Salvador
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: Quebec City
country: Canada
facility: Research Site
state: Quebec
city: Sherbrooke
country: Canada
facility: Research Site
state: Quebec
city: Osorno
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Viña del Mar
country: Chile
facility: Research Site
city: Bordeaux Cedex
country: France
facility: Research Site
city: LE KREMLIN-BICETRE Cedex
country: France
facility: Research Site
city: Paris Cedex 13
country: France
facility: Research Site
city: Strasbourg Cedex
country: France
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Dresden
country: Germany
facility: Research Site
city: Frankfurt
country: Germany
facility: Research Site
city: Kiel
country: Germany
facility: Research Site
city: Köln
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: Mainz
country: Germany
facility: Research Site
city: Münster
country: Germany
facility: Research Site
city: Regensburg
country: Germany
facility: Research Site
city: Würzburg
country: Germany
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Debrecen
country: Hungary
facility: Research Site
city: Miskolc
country: Hungary
facility: Research Site
city: Zalaegerszeg
country: Hungary
facility: Research Site
city: Bangalore
country: India
facility: Research Site
city: Secunderabad
country: India
facility: Research Site
city: Brescia
country: Italy
facility: Research Site
city: Firenze
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Padova
country: Italy
facility: Research Site
city: Pisa
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Kingston
country: Jamaica
facility: Research Site
city: Chihuahua
country: Mexico
facility: Research Site
city: Guadalajara
country: Mexico
facility: Research Site
city: Mexico
country: Mexico
facility: Research Site
city: México
country: Mexico
facility: Research Site
city: San Luis Potosi
country: Mexico
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: San Borja
country: Peru
facility: Research Site
city: Cebu City
country: Philippines
facility: Research Site
city: Iloilo City
country: Philippines
facility: Research Site
city: Manila
country: Philippines
facility: Research Site
city: Białystok
country: Poland
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Katowice
country: Poland
facility: Research Site
city: Kraków
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Olsztyn
country: Poland
facility: Research Site
city: Poznań
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Brasov
country: Romania
facility: Research Site
city: Bucharest
country: Romania
facility: Research Site
city: Bucuresti
country: Romania
facility: Research Site
city: Cluj Napoca
country: Romania
facility: Research Site
city: Tg Mures
country: Romania
facility: Research Site
city: Cape Town
country: South Africa
facility: Research Site
city: Durban
country: South Africa
facility: Research Site
city: Johannesburg
country: South Africa
facility: Research Site
city: Pinelands
country: South Africa
facility: Research Site
city: Soweto
country: South Africa
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Guadalajara
country: Spain
facility: Research Site
city: La Laguna (Tenerife)
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Majadahonda
country: Spain
facility: Research Site
city: Malaga
country: Spain
facility: Research Site
city: Mérida
country: Spain
facility: Research Site
city: Santiago de Compostela
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Brighton
country: United Kingdom
facility: Research Site
city: Cambridge
country: United Kingdom
facility: Research Site
city: Cannock
country: United Kingdom
facility: Research Site
city: Guildford
country: United Kingdom
facility: Research Site
city: Leeds
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
Study officials:
affiliation: MedImmune LLC
name: Gabor Illei, MD
role: STUDY_DIRECTOR
References:
citation: 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.
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: 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.