A Study of the Efficacy and Safety of MEDI-546 in Systemic Lupus Erythematosus

NCT01438489 | Completed Phase 2 Results DMC

• 1 other identifier: CD-IA-MEDI-546-1013
• Study Type: interventional
• Target: 626
• Locations: 14 countries
• Sites: 79

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.

Conditions

Systemic Lupus Erythematosus

Keywords

MEDI-546; Anifrolumab; Systemic Lupus Erythematosus

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants Achieving an Systemic Lupus Erythematosus (SLE) Responder Index [SRI (4)] Response With Oral Corticosteroids (OCS) Tapering at Day 169

  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.

  Day 169

• 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

  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.

  Day 169

Secondary Outcomes (12)

• Percentage of Participants Achieving an Systemic Lupus Erythematosus (SLE) Responder Index [SRI (4)] Response With Oral Corticosteroids (OCS) Tapering at Day 365

  Day 365

• 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

  Day 365

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESIs) and Treatment-Emergent Serious Adverse Events (TESAEs)

  Day 1 (Baseline) to Day 422 (End of Study)

• Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events

  Day 1 (Baseline) to Day 422 (End of Study)

• Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs)

  Day 1 (Baseline) to Day 422 (End of Study)

Study Arms (3)

Anifrolumab (MEDI-546) 300 mg

EXPERIMENTAL

Participants will receive 300 milligram (mg) anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.

Biological: Anifrolumab 300 mg

Anifrolumab (MEDI-546) 1000 mg

EXPERIMENTAL

Participants will receive 1000 mg anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.

Biological: Anifrolumab 1000 mg

Matching Placebo

PLACEBO COMPARATOR

Participants will receive placebo matched to anifrolumab intravenous (IV) infusion every 4 weeks for 48 weeks.

Other: Placebo

Interventions

Anifrolumab 300 mg BIOLOGICAL

Participants will receive 300 milligram (mg) anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.

Also known as: MEDI-546

Anifrolumab (MEDI-546) 300 mg

Anifrolumab 1000 mg BIOLOGICAL

Participants will receive 1000 mg anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.

Also known as: MEDI-546

Anifrolumab (MEDI-546) 1000 mg

Placebo OTHER

Participants will receive placebo matched to anifrolumab intravenous (IV) infusion every 4 weeks for 48 weeks.

Matching Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• MedImmune LLC: lead

Study Sites (79)

Research Site

Birmingham, Alabama, United States

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La Jolla, California, United States

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La Palma, California, United States

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Long Beach, California, United States

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Los Angeles, California, United States

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Palm Desert, California, United States

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San Leandro, California, United States

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Upland, California, United States

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Miami, Florida, United States

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Ocala, Florida, United States

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Orlando, Florida, United States

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Palm Harbor, Florida, United States

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Tampa, Florida, United States

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Atlanta, Georgia, United States

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Decatur, Georgia, United States

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Stockbridge, Georgia, United States

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Idaho Falls, Idaho, United States

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Chicago, Illinois, United States

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Indianapolis, Indiana, United States

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Las Cruces, New Mexico, 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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Columbus, Ohio, United States

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Edmond, Oklahoma, United States

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Tulsa, Oklahoma, United States

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Memphis, Tennessee, United States

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Houston, Texas, United States

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Seattle, Washington, United States

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Spokane, Washington, United States

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Rio de Janeiro, Brazil

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São Paulo, Brazil

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Plovdiv, Bulgaria

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Sofia, Bulgaria

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Barranquilla, Colombia

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Bogotá, Colombia

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Bucaramanga, Colombia

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Chía, Colombia

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Medellín, Colombia

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Brno, Czechia

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Prague, Czechia

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Uherské Hradiště, Czechia

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Budapest, Hungary

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Debrecen, Hungary

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Dantoli-Nagpur, India

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Hyderabad, India

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Mumbai, India

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New Delhi, India

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Pune, India

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Secunderabad, India

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Guadalajara, Mexico

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León, Mexico

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México, Mexico

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Toluca, Mexico

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Arequipa, Peru

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Lima, Peru

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Bialystok, Poland

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Bydgoszcz, Poland

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Krakow, Poland

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Nadarzyn, Poland

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Poznan, Poland

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Brasov, Romania

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Iași, Romania

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Târgu Mureş, Romania

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Gwangjin-gu, South Korea

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Gwangju, South Korea

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Seodaemun-gu, South Korea

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Suwon, South Korea

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Chiayi City, Taiwan

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Kaohsiung City, Taiwan

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Taichung, Taiwan

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Taipei, Taiwan

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Donetsk, Ukraine

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Kyiv, Ukraine

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Luhansk, Ukraine

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Lviv, Ukraine

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Ternopil, Ukraine

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Vinnitsya, Ukraine

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Vinnytsia, Ukraine

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Related Publications (6)

• 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.

  PMID: 33687069 DERIVED

• 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.

  PMID: 32909675 DERIVED

• 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.

  PMID: 31660791 DERIVED

• 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.

  PMID: 30538817 DERIVED

• Morand EF, Trasieva T, Berglind A, Illei GG, Tummala R. Lupus Low Disease Activity State (LLDAS) attainment discriminates responders in a systemic lupus erythematosus trial: post-hoc analysis of the Phase IIb MUSE trial of anifrolumab. Ann Rheum Dis. 2018 May;77(5):706-713. doi: 10.1136/annrheumdis-2017-212504. Epub 2018 Feb 2.

  PMID: 29420200 DERIVED

• 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.

  PMID: 28130918 DERIVED

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

anifrolumab

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Gabor Illei, MD, Senior Director
• Organization: MedImmune, LLC

illeig@Medimmune.com

301-398-0000

Study Officials

• Warren Greth, MD

  MedImmune LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2011
• First Posted: September 22, 2011
• Study Start: January 1, 2012
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: October 7, 2016
• Results First Posted: August 15, 2016

Record last verified: 2016-08

Locations

PE (2); TW (4); HU (2); BU (2); CZ (3); CO (5); IN (6); UA (7); BR (2); PL (5); KR (4); US (30); ME (4); RO (3)