Safety Study of AMG 557 in Subjects With Lupus Arthritis

A Randomized, Double-blind, Parallel, Placebo-controlled, Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Clinical Effect of AMG 557 in Systemic Lupus Erythematosus (SLE) Subjects With Active Lupus Arthritis

This is a multicenter, randomized, double-blind, parallel, placebo-controlled, multiple dose study that will enroll approximately 40 systemic lupus erythematosus subjects with active lupus arthritis.

Study Overview

• Status: Completed
• Conditions: Lupus Arthritis, Systemic Lupus Erythematosus
• Intervention / Treatment: Drug: AMG 557; Drug: Matching Placebo

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • St Leonards, New South Wales, Australia, 2065
      • Research Site
• Denmark
  • Odense, Denmark, 5000
    • Research Site
• France
  • Lille cedex 01, France, 59037
    • Research Site
• Germany
  • Berlin, Germany, 10117
    • Research Site
• Malaysia
  • Sarawak
    • Kuching, Sarawak, Malaysia, 93586
      • Research Site
  • Wilayah Persekutuan
    • Kuala Lumpur, Wilayah Persekutuan, Malaysia, 59100
      • Research Site
• Taiwan
  • Taipei, Taiwan, 10002
    • Research Site
• United Kingdom
  • Birmingham, United Kingdom, B18 7QH
    • Research Site
  • London, United Kingdom, WC1E 6JF
    • Research Site
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Research Site
    • San Leandro, California, United States, 94578
      • Research Site
  • Connecticut
    • Danbury, Connecticut, United States, 06810
      • Research Site
  • New York
    • Manhasset, New York, United States, 11030
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of SLE for at least 6 months as defined by the most recent American College of Rheumatology criteria
• Presence of lupus related inflammatory arthritis with at least four tender and four swollen joints; and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) ≥ 6 at screening;
• Other inclusion criteria may apply.

Exclusion Criteria:

• Presence or history of vasculitis, and presence or history of active lupus nephritis requiring therapy within the last 3 years
• Any disorder (including psychiatric), condition, clinically significant disease, disease activity related to SLE
• Positive for HIV antibodies, hepatitis B surface antigen or anti-HBc, or hepatitis C antibodies
• Known residential exposure to an individual with tuberculosis or positive Quantiferon test or PPD test at screening
• Men and women of reproductive potential, unwilling to practice a highly effective method of birth control for the duration of the study
• Other exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: AMG 557; All will receive AMG 557 on Day 1, Day 8, Day 15, Day 29, Day 43, Day 57, Day 71, Day 85, Day 99, Day 113, Day 127, Day 141 and Day 155.	Drug: AMG 557; AMG 557 will be administered as subcutaneous injections in the anterior abdomen of the subjects.
PLACEBO_COMPARATOR: AMG 557 Matching Placebo; All will receive AMG 557 on Day 1, Day 8, Day 15, Day 29, Day 43, Day 57, Day 71, Day 85, Day 99, Day 113, Day 127, Day 141 and Day 155.	Drug: Matching Placebo; Placebo will be administered as subcutaneous injections in the anterior abdomen of the subjects.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-emergent adverse events, vital signs, physical examinations, clinical laboratory tests, ECGs, and the incidence of binding and neutralizing antibodies to AMG 557.		330 days, including a 21-day screening period
Lupus Arthritis Response Rate	Defined by: 1) achieving at least a 50% decrease in the combined tender and swollen joint count compared to baseline at Day 169; 2) achieving one letter improvement in the Musculoskeletal System BILAG at Day 169 compared to baseline; 3) reduction in and maintenance of prednisone (or its equivalent) dose to ≤ 50% of baseline corticosteroid dose (Day 1 predose) or ≤ 7.5 mg/day, whichever is lower, from Day 85 to Day 169 in subjects not treated with immunosuppressants at baseline, or reduction in and maintenance of prednisone (or its equivalent) dose to ≤ 7.5 mg/day from Day 85 to Day 169 and discontinuation of immunosuppressants by Day 29 in subjects treated with immunosuppressants at baseline	Day 169

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of subjects achieving a) one letter improvement; and b) 'C' or better score in the Musculoskeletal system from BILAG index at Day 169 compared to baseline, by treatment group.	Day 169
Percentage change in the tender and swollen joint counts at Day 169 relative to baseline.	Day 169
Proportion of subjects achieving reduction in and maintenance ≤ 7.5 mg/day of prednisone (or equivalent) from Day 85- Day 169 and discontinuation of immunosuppressants by Day 29 in subjects treated with immunosuppressants at baseline.	Days 85-169
Proportion of subjects achieving reduction in and maintenance of prednisone (or its	Days 85-169
Physician Global Assessment of Disease Activity (PGADA).	330 days, including a 21-day screening period
Subject Global Assessment of Disease Activity (SGADA).	330 days, including a 21-day screening period
Serum PK profile of AMG 557 after multiple dose administrations.	330 days, including a 21-day screening period
Proportion of subjects who discontinued immunosuppressants by Day 29 in subjects	Day 29
Cumulative dose of prednisone (or its equivalent) from Day 85 to Day 169.	Day 85 to Day 169

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• Cheng LE, Amoura Z, Cheah B, Hiepe F, Sullivan BA, Zhou L, Arnold GE, Tsuji WH, Merrill JT, Chung JB. Brief Report: A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Multiple-Dose Study to Evaluate AMG 557 in Patients With Systemic Lupus Erythematosus and Active Lupus Arthritis. Arthritis Rheumatol. 2018 Jul;70(7):1071-1076. doi: 10.1002/art.40479. Epub 2018 May 25.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (ACTUAL): March 1, 2016
• Study Completion (ACTUAL): March 1, 2016

Study Registration Dates

• First Submitted: March 14, 2012
• First Submitted That Met QC Criteria: September 10, 2012
• First Posted (ESTIMATE): September 12, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): January 24, 2017
• Last Update Submitted That Met QC Criteria: January 20, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Lupus Arthritis, Systemic Lupus Erythematosus, AMG 557, Lupus
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Connective Tissue Diseases; Arthritis; Lupus Erythematosus, Systemic
• Other Study ID Numbers: 20101103