A Study to Evaluate the Efficacy and Safety of Sifalimumab in Adults With Systemic Lupus Erythematosus

NCT ID: NCT01283139

Last Updated: 2018-04-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 834 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-31
• Study Completion Date: 2014-04-17

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.

Conditions

Systemic Lupus Erythematosus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Sifalimumab 200 milligram (mg)

Sifalimumab 200 milligram (mg) will be administered intravenously every 2 weeks for 4 weeks and then monthly for 44 weeks for a total of 14 doses.

Group Type: EXPERIMENTAL

Sifalimumab 200 mg

Intervention Type: BIOLOGICAL

Sifalimumab 200 mg intravenously every 2 weeks for 4 weeks and then monthly for 44 weeks for a total of 14 doses.

Sifalimumab 600 mg

Sifalimumab 600 mg will be administered intravenously every 2 weeks for 4 weeks and then monthly for 44 weeks for a total of 14 doses.

Group Type: EXPERIMENTAL

Sifalimumab 600 mg

Intervention Type: BIOLOGICAL

Sifalimumab 600 mg intravenously every 2 weeks for 4 weeks and then monthly for 44 weeks for a total of 14 doses.

Sifalimumab 1,200 mg

Sifalimumab 1,200 mg will be administered intravenously every 2 weeks for 4 weeks and then monthly for 44 weeks for a total of 14 doses.

Group Type: EXPERIMENTAL

Sifalimumab 1,200 mg

Intervention Type: BIOLOGICAL

Sifalimumab 1,200 mg intravenously every 2 weeks for 4 weeks and then monthly for 44 weeks for a total of 14 doses.

Placebo

Placebo matching to sifalimumab will be administered intravenously at a fixed dose every 2 weeks for 4 weeks and then monthly for 44 weeks for a total of 14 doses.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

IV Placebo every 2 weeks for 4 weeks and then monthly for 44 weeks

Interventions

Sifalimumab 200 mg

Sifalimumab 200 mg intravenously every 2 weeks for 4 weeks and then monthly for 44 weeks for a total of 14 doses.

Intervention Type: BIOLOGICAL

Sifalimumab 600 mg

Sifalimumab 600 mg intravenously every 2 weeks for 4 weeks and then monthly for 44 weeks for a total of 14 doses.

Intervention Type: BIOLOGICAL

Sifalimumab 1,200 mg

Sifalimumab 1,200 mg intravenously every 2 weeks for 4 weeks and then monthly for 44 weeks for a total of 14 doses.

Intervention Type: BIOLOGICAL

Placebo

IV Placebo every 2 weeks for 4 weeks and then monthly for 44 weeks

Intervention Type: OTHER

Other Intervention Names

MEDI-545; MEDI-545; MEDI-545

Eligibility Criteria

Inclusion 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

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

MedImmune LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gabor Illei, MD

Role: STUDY_DIRECTOR

MedImmune LLC

Locations

Research Site

La Jolla, California, United States

Research Site

Palm Desert, California, United States

Research Site

San Leandro, California, United States

Research Site

Fort Lauderdale, Florida, United States

Research Site

Orlando, Florida, United States

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Stockbridge, Georgia, United States

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Idaho Falls, Idaho, United States

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Shreveport, Louisiana, United States

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Baltimore, Maryland, United States

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Lansing, Michigan, United States

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Brooklyn, New York, United States

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Manhasset, New York, United States

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New York, New York, United States

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Charlotte, North Carolina, United States

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Raleigh, North Carolina, United States

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Dallas, Texas, United States

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Seattle, Washington, United States

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Buenos Aires, , Argentina

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Ciudad Autonoma de Buenos Aire, , Argentina

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Ciudad de Buenos Aires, , Argentina

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La Plata, , Argentina

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Quilmes, , Argentina

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San Miguel de Tucumán, , Argentina

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Curitiba, , Brazil

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Goiânia, , Brazil

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Juiz de Fora, , Brazil

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Porto Alegre, , Brazil

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Salvador, , Brazil

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São Paulo, , Brazil

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Plovdiv, , Bulgaria

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Sofia, , Bulgaria

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Québec, Quebec, Canada

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Sherbrooke, Quebec, Canada

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Osorno, , Chile

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Santiago, , Chile

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Viña del Mar, , Chile

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Bordeaux, , France

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Le Kremlin-Bicêtre, , France

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Paris, , France

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Strasbourg, , France

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Berlin, , Germany

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Cologne, , Germany

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Dresden, , Germany

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Frankfurt, , Germany

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Kiel, , Germany

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Leipzig, , Germany

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Mainz, , Germany

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Münster, , Germany

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Regensburg, , Germany

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Würzburg, , Germany

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Budapest, , Hungary

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Debrecen, , Hungary

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Miskolc, , Hungary

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Zalaegerszeg, , Hungary

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Bangalore, , India

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Secunderabad, , India

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Brescia, , Italy

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Florence, , Italy

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Milan, , Italy

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Padua, , Italy

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Pisa, , Italy

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Roma, , Italy

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Kingston, , Jamaica

Research Site

Chihuahua City, , Mexico

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Guadalajara, , Mexico

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México, , Mexico

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San Luis Potosí City, , Mexico

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Amsterdam, , Netherlands

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Lima, , Peru

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San Borja, , Peru

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Cebu City, , Philippines

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Iloilo City, , Philippines

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Manila, , Philippines

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Bialystok, , Poland

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Bydgoszcz, , Poland

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Katowice, , Poland

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Krakow, , Poland

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Lublin, , Poland

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Olsztyn, , Poland

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Poznan, , Poland

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Warsaw, , Poland

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Brasov, , Romania

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Bucharest, , Romania

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Cluj-Napoca, , Romania

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Tg Mures, , Romania

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Cape Town, , South Africa

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Durban, , South Africa

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Johannesburg, , South Africa

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Pinelands, , South Africa

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Soweto, , South Africa

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Barcelona, , Spain

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Guadalajara, , Spain

Research Site

La Laguna (Tenerife), , Spain

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Madrid, , Spain

Research Site

Majadahonda, , Spain

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Málaga, , Spain

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Mérida, , Spain

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Santiago de Compostela, , Spain

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Seville, , Spain

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Bangkok, , Thailand

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Brighton, , United Kingdom

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Cambridge, , United Kingdom

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Cannock, , United Kingdom

Research Site

Guildford, , United Kingdom

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Leeds, , United Kingdom

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London, , United Kingdom

Research Site

Manchester, , United Kingdom

Countries

United States; Argentina; Brazil; Bulgaria; Canada; Chile; France; Germany; Hungary; India; Italy; Jamaica; Mexico; Netherlands; Peru; Philippines; Poland; Romania; South Africa; Spain; Thailand; United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 27009916 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33687069 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31660791 (View on PubMed)

Other Identifiers

2010-024069-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CD-IA-MEDI-545-1067

Identifier Type: -

Identifier Source: org_study_id