Safety Study of AMG 557 in Subjects With Lupus Arthritis
Primary Purpose
Lupus Arthritis, Systemic Lupus Erythematosus
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
AMG 557
Matching Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Lupus Arthritis, Systemic Lupus Erythematosus focused on measuring Lupus Arthritis, Systemic Lupus Erythematosus, AMG 557, Lupus
Eligibility Criteria
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
Sites / Locations
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
AMG 557
AMG 557 Matching Placebo
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Treatment-emergent adverse events, vital signs, physical examinations, clinical laboratory tests, ECGs, and the incidence of binding and neutralizing antibodies to AMG 557.
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
Secondary Outcome Measures
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.
Percentage change in the tender and swollen joint counts at Day 169 relative to baseline.
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.
Proportion of subjects achieving reduction in and maintenance of prednisone (or its
Physician Global Assessment of Disease Activity (PGADA).
Subject Global Assessment of Disease Activity (SGADA).
Serum PK profile of AMG 557 after multiple dose administrations.
Proportion of subjects who discontinued immunosuppressants by Day 29 in subjects
Cumulative dose of prednisone (or its equivalent) from Day 85 to Day 169.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01683695
Brief Title
Safety Study of AMG 557 in Subjects With Lupus Arthritis
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2017
Overall Recruitment Status
Completed
Study Start Date
June 2012 (undefined)
Primary Completion Date
March 2016 (Actual)
Study Completion Date
March 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lupus Arthritis, Systemic Lupus Erythematosus
Keywords
Lupus Arthritis, Systemic Lupus Erythematosus, AMG 557, Lupus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AMG 557
Arm Type
Active Comparator
Arm Description
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.
Arm Title
AMG 557 Matching Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
AMG 557
Intervention Description
AMG 557 will be administered as subcutaneous injections in the anterior abdomen of the subjects.
Intervention Type
Drug
Intervention Name(s)
Matching Placebo
Intervention Description
Placebo will be administered as subcutaneous injections in the anterior abdomen of the subjects.
Primary Outcome Measure Information:
Title
Treatment-emergent adverse events, vital signs, physical examinations, clinical laboratory tests, ECGs, and the incidence of binding and neutralizing antibodies to AMG 557.
Time Frame
330 days, including a 21-day screening period
Title
Lupus Arthritis Response Rate
Description
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
Time Frame
Day 169
Secondary Outcome Measure Information:
Title
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.
Time Frame
Day 169
Title
Percentage change in the tender and swollen joint counts at Day 169 relative to baseline.
Time Frame
Day 169
Title
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.
Time Frame
Days 85-169
Title
Proportion of subjects achieving reduction in and maintenance of prednisone (or its
Time Frame
Days 85-169
Title
Physician Global Assessment of Disease Activity (PGADA).
Time Frame
330 days, including a 21-day screening period
Title
Subject Global Assessment of Disease Activity (SGADA).
Time Frame
330 days, including a 21-day screening period
Title
Serum PK profile of AMG 557 after multiple dose administrations.
Time Frame
330 days, including a 21-day screening period
Title
Proportion of subjects who discontinued immunosuppressants by Day 29 in subjects
Time Frame
Day 29
Title
Cumulative dose of prednisone (or its equivalent) from Day 85 to Day 169.
Time Frame
Day 85 to Day 169
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Research Site
City
San Leandro
State/Province
California
ZIP/Postal Code
94578
Country
United States
Facility Name
Research Site
City
Danbury
State/Province
Connecticut
ZIP/Postal Code
06810
Country
United States
Facility Name
Research Site
City
Manhasset
State/Province
New York
ZIP/Postal Code
11030
Country
United States
Facility Name
Research Site
City
St Leonards
State/Province
New South Wales
ZIP/Postal Code
2065
Country
Australia
Facility Name
Research Site
City
Odense
ZIP/Postal Code
5000
Country
Denmark
Facility Name
Research Site
City
Lille cedex 01
ZIP/Postal Code
59037
Country
France
Facility Name
Research Site
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Research Site
City
Kuching
State/Province
Sarawak
ZIP/Postal Code
93586
Country
Malaysia
Facility Name
Research Site
City
Kuala Lumpur
State/Province
Wilayah Persekutuan
ZIP/Postal Code
59100
Country
Malaysia
Facility Name
Research Site
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan
Facility Name
Research Site
City
Birmingham
ZIP/Postal Code
B18 7QH
Country
United Kingdom
Facility Name
Research Site
City
London
ZIP/Postal Code
WC1E 6JF
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
29513931
Citation
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.
Results Reference
derived
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website
Learn more about this trial
Safety Study of AMG 557 in Subjects With Lupus Arthritis
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