An Open-label Study to Evaluate the Long-term Safety of MEDI-546, for the Treatment of SLE, in Adults

A Phase 2, Open-label Extension Study to Evaluate Long-term Safety of MEDI-546 in Adults With Systemic Lupus Erythematosus

The purpose of this study is to evaluate the long-term safety of anifrolumab (MEDI-546) in adults with moderate to severe active systemic lupus erythematosus (SLE).

Study Overview

• Status: Completed
• Conditions: Lupus Erythematosus, Systemic
• Intervention / Treatment: Biological: Anifrolumab

Detailed Description

This is an open-label extension study to evaluate long-term safety and tolerability of intravenous (IV) anifrolumab in adult participants with moderately-to-severely active SLE. Participants must have completed the qualifying Phase 2 study and meet this study criteria in order to be eligible.

• Study Type: Interventional
• Enrollment (Actual): 218
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Rio de Janeiro, Brazil, 22040-042
    • Research Site
  • Sao Paulo, Brazil, 04032-060
    • Research Site
• Bulgaria
  • Plovdiv, Bulgaria, 4002
    • Research Site
  • Sofia, Bulgaria, 1431
    • Research Site
• Colombia
  • Barranquilla, Colombia
    • Research Site
  • Bogota, Colombia
    • Research Site
  • Bucaramanga, Colombia
    • Research Site
  • Chia, Colombia
    • Research Site
  • Medellin, Colombia
    • Research Site
• Czechia
  • Brno, Czechia
    • Research Site
  • Praha 2, Czechia
    • Research Site
• Hungary
  • Debrecen, Hungary
    • Research Site
• Korea, Republic of
  • Gwangju, Korea, Republic of
    • Research Site
  • Seodaemun-gu, Korea, Republic of
    • Research Site
  • Suwon-si, Korea, Republic of, 16499
    • Research Site
• Mexico
  • Guadalajara, Mexico
    • Research Site
  • Leon, Mexico
    • Research Site
  • Mexico, Mexico
    • Research Site
  • Toluca, Mexico
    • Research Site
• Peru
  • Arequipa, Peru
    • Research Site
  • Lima, Peru
    • Research Site
  • Lima, Peru, 15033
    • Research Site
• Poland
  • Bialystok, Poland, 15-297
    • Research Site
  • Krakow, Poland, 31-011
    • Research Site
  • Nadarzyn, Poland, 05-830
    • Research Site
  • Poznan, Poland, 61-397
    • Research Site
• Romania
  • Iasi, Romania, 700661
    • Research Site
• Taiwan
  • Chiayi, Taiwan, 622
    • Research Site
  • Zhongzheng District, Taiwan
    • Research Site
• Ukraine
  • Donetsk, Ukraine
    • Research Site
  • Kyiv, Ukraine
    • Research Site
  • Ternopil, Ukraine
    • Research Site
  • Vinnitsya, Ukraine, 21029
    • Research Site
  • Vinnytsia, Ukraine, 21018
    • Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Research Site
  • California
    • La Palma, California, United States, 90623
      • Research Site
    • Long Beach, California, United States, 90806
      • Research Site
    • Los Angeles, California, United States, 90095-1670
      • Research Site
    • Palm Desert, California, United States, 92260
      • Research Site
    • Upland, California, United States, 91786
      • Research Site
  • Florida
    • Ocala, Florida, United States, 34474
      • Research Site
    • Orlando, Florida, United States, 32806
      • Research Site
    • Tampa, Florida, United States, 33614
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30281
      • Research Site
    • Stockbridge, Georgia, United States, 30281
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Research Site
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Research Site
  • New Mexico
    • Las Cruces, New Mexico, United States, 88011
      • Research Site
  • New York
    • New York, New York, United States, 10016
      • Research Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Research Site
    • Raleigh, North Carolina, United States, 27617
      • Research Site
  • Ohio
    • Columbus, Ohio, United States, 43203
      • Research Site
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74104
      • Research Site
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Research Site
  • Texas
    • Houston, Texas, United States, 77034
      • Research Site
    • Houston, Texas, United States, 77004
      • Research Site
  • Washington
    • Spokane, Washington, United States, 99204
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Must be willing to use 2 methods of effective contraception
• Must have venous access
• Must be willing to forego participation in other clinical trials for SLE.

Exclusion Criteria:

• Any concurrent condition that in the opinion of the investigator would interfere with the evaluation of the investigational product
• Major surgery within 8 weeks before signing informed consent form (ICF)
• Elective major surgery planned during the study period
• Concomitant Medications within the last 12 weeks: Azathioprine > 200 mg/day, Mycophenolate mofetil/mycophenolic acid > 2.0 g/day, oral, subcutaneous, or intramuscular methotrexate > 25 mg/week
• A live or attenuated vaccine within 4 weeks of signing the ICF
• Bacillus of Calmette and Guérin (BCG) vaccine within 1 year of ICF

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anifrolumab; Participants will receive IV infusion of anifrolumab 1000 milligrams (mg) every 4 weeks (Q4W) from Day 1 (Week 0) until 12-Feb-2015 (approval of protocol amendment 4); and thereafter will receive 300 mg Q4W for up to 3 years or until the sponsor discontinued development of anifrolumab, whichever came first.	Biological: Anifrolumab; Intravenous infusion of anifrolumab will be administered as 1000 mg Q4W from Day 1 (Week 0) until 12-Feb-2015 (approval of protocol amendment 4); and thereafter 300 mg Q4W up to 3 years or until the sponsor discontinued development of anifrolumab, whichever came first.; Other Names: MEDI-546

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Particpants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event is any AE that resulted in death, life threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, is a congenital anomaly/birth defect in offspring of a study participant, is an important medical event that may jeopardize the participant or may require medical intervention. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.	From first dose of study drug (Day 1) through 168 weeks
Number of Participants With Adverse Events Resulting in Discontinuation (DAEs) of Anifrolumab	Number of participants with DAEs are reported.	From first dose of study drug (Day 1) through 168 weeks
Number of Participants With Adverse Events of Special Interest (AESIs)	An AESI is scientific and medical concern specific to understanding of the study drug. An AESI may be serious or non-serious. Number of participants with AESIs are reported.	From first dose of study drug (Day 1) through 168 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Anifrolumab	The number of participants with positive serum antibodies to anifrolumab at anytime (including baseline) are reported.	Baseline (Pre-dose on Day 1) up to Week 168
Anti-Drug Antibodies (ADA) Titer to Anifrolumab	Median ADA titer in participants with ADA-positive assessments and reportable ADA titer results are reported.	Baseline (Pre-dose on Day 1) up to Week 168
Number of ADA-positive Participants With Decreased Serum Concentration of Anifrolumab	Number of participants with decreased serum concentration of anifrolumab due to ADA-positive results are reported.	Baseline (Pre-dose on Day 1) up to Week 168
Number of ADA-positive Participants With Decreased Pharmacodynamics Response of Anifrolumab	Number of participants with decreased pharmacodynamic response of anifrolumab due to ADA-positive results are reported.	Baseline (Pre-dose on Day 1) up to Week 168
Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Global Score for ADA Positive Participants	The SLEDAI-2K is an activity index that measures disease activity and records feature of active lupus as present or not present. SLEDAI-2K uses a weighted checklist to assign a numerical score based on the presence or absence of 24 symptoms. Each symptom present is assigned between 1 and 8 points based on its usual clinical importance, yielding a total score that ranges from 0 points (no symptoms) to 105 points (presence of all defined symptoms).	Baseline (Pre-dose on Day 1); and Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 160, and 168
Number of ADA-positive Participants With TEAEs and TESAEs	The number of ADA-positive participants with TEAEs and TESAEs are reported.	Baseline (Pre-dose on Day 1) up to Week 168

Collaborators and Investigators

• Sponsor: MedImmune LLC

Publications and helpful links

General Publications

• Chatham WW, Furie R, Saxena A, Brohawn P, Schwetje E, Abreu G, Tummala R. Long-Term Safety and Efficacy of Anifrolumab in Adults With Systemic Lupus Erythematosus: Results of a Phase II Open-Label Extension Study. Arthritis Rheumatol. 2021 May;73(5):816-825. doi: 10.1002/art.41598. Epub 2021 Mar 24. Erratum In: Arthritis Rheumatol. 2021 Aug;73(8):1570.

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2013
• Primary Completion (Actual): July 18, 2018
• Study Completion (Actual): July 18, 2018

Study Registration Dates

• First Submitted: December 17, 2012
• First Submitted That Met QC Criteria: December 17, 2012
• First Posted (Estimate): December 20, 2012

Study Record Updates

• Last Update Posted (Actual): July 31, 2019
• Last Update Submitted That Met QC Criteria: July 11, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Systemic Lupus Erythematosus
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: CD-IA-MEDI-546-1145; 2012-004619-30 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: AstraZeneca's policy is to share data with researchers if the request is in scope of our policy. Additional information can be found on astrazenecaclinicaltrials.com.