Safety Study of AMG 557 in Subjects With Lupus Arthritis - Full Text View

Purpose

This study will be a multicenter, randomized, double-blind, placebo-controlled, multiple dose, parallel, multiple dose level design study will enroll approximately 40 systemic lupus erythematosus subjects with active lupus arthritis, divided into two cohorts. Cohort 1 will consist of 20 subjects randomized to receive 210 mg of AMG 557 or matching placebo. Cohort 2 will consist of 20 subjects randomized to receive 210mg AMG 557, or 140 mg of AMG 557 or matching placebo.

Condition	Intervention	Phase
Lupus Arthritis, Systemic Lupus Erythematosus	Drug: AMG 557 210 mg Drug: 210 mg Matching Placebo Drug: AMG 557 140 mg Drug: 140 mg Matching Placebo	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Randomized, Double-blind, Placebo-controlled, Multiple Dose, Parallel, Multiple Dose-Level Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Clinical Effect of AMG 557 in Systemic Lupus Erythematosus (SLE) Subjects With Active Lupus Arthritis

Resource links provided by NLM:

MedlinePlus related topics: Lupus

U.S. FDA Resources

Further study details as provided by Amgen:

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. [ Time Frame: 330 days, including a 21-day screening period ] [ Designated as safety issue: Yes ]
Lupus Arthritis Response Rate [ Time Frame: Day 169 ] [ Designated as safety issue: No ]
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) on ≤ 7.5 mg/d of prednisone or its equivalent from Day 85 to Day 169)

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. [ Time Frame: Day 169 ] [ Designated as safety issue: No ]
Percentage change in the tender and swollen joint counts at Day 169 relative to baseline. [ Time Frame: Day 169 ] [ Designated as safety issue: No ]
Proportion of subjects on ≤ 7.5 mg/day of prednisone (or equivalent) by Day 85, by treatment group. [ Time Frame: Day 85 ] [ Designated as safety issue: No ]
Cumulative dose of prednisone (or equivalent) from Day 85 to Day 169. [ Time Frame: Days 85-169 ] [ Designated as safety issue: No ]
Physician Global Assessment of Disease Activity (PGADA). [ Time Frame: 330 days, including a 21-day screening period ] [ Designated as safety issue: No ]
Subject Global Assessment of Disease Activity (SGADA). [ Time Frame: 330 days, including a 21-day screening period ] [ Designated as safety issue: No ]
Serum PK profile of AMG 557 after multiple dose administrations. [ Time Frame: 330 days, including a 21-day screening period ] [ Designated as safety issue: No ]

Estimated Enrollment:	40
Study Start Date:	January 2012
Estimated Study Completion Date:	August 2014
Estimated Primary Completion Date:	August 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: AMG 557 210 mg 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 557 210 mg AMG 557 (210 mg) will be administered as subcutaneous injections in the anterior abdomen of the subjects. 20 subjects will be randomized to receive AMG 557. Beginning on Day 1, subjects will receive AMG 557 once weekly for 3 weeks on Day 1, Day 8, and Day 15 and following with 10 additional doses of AMG 557 every other week on Day 29, Day 43, Day 57, Day 71, Day 85, Day 99, Day 113, Day 127, Day 141 and Day 155.
Placebo Comparator: AMG 557 210 mg 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: 210 mg Matching Placebo Placebo will be administered as subcutaneous injections in the anterior abdomen of the subjects. 20 subjects will be randomized to receive placebo. Beginning on Day 1, subjects will receive placebo once weekly for 3 weeks on Day 1, Day 8, and Day 15 and following with 10 additional doses of placebo every other week on Day 29, Day 43, Day 57, Day 71, Day 85, Day 99, Day 113, Day 127, Day 141 and Day 155.
Active Comparator: AMG 557 140 mg 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 557 140 mg AMG 557 (140 mg) will be administered as subcutaneous injections in the anterior abdomen of the subjects. 20 subjects will be randomized to receive AMG 557. Beginning on Day 1, subjects will receive AMG 557 once weekly for 3 weeks on Day 1, Day 8, and Day 15 and following with 10 additional doses of AMG 557 every other week on Day 29, Day 43, Day 57, Day 71, Day 85, Day 99, Day 113, Day 127, Day 141 and Day 155.
Placebo Comparator: AMG 557 140 mg 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: 140 mg Matching Placebo Placebo will be administered as subcutaneous injections in the anterior abdomen of the subjects. 20 subjects will be randomized to receive placebo. Beginning on Day 1, subjects will receive placebo once weekly for 3 weeks on Day 1, Day 8, and Day 15 and following with 10 additional doses of placebo every other week on Day 29, Day 43, Day 57, Day 71, Day 85, Day 99, Day 113, Day 127, Day 141 and Day 155.

Detailed Description:

This multi-center, randomized, double-blind, placebo-controlled, multiple dose, parallel, multiple dose level design study will enroll approximately 40 subjects with lupus arthritis, divided into two cohorts. Cohort 1 will consist of twenty subjects (n=20) randomized (1:1) to receive AMG 557 (210 mg dose) or matching placebo. Cohort 2, will consist of twenty subjects (n=20) randomized (1:1) to receive AMG 557 (210 mg or 140 mg dose) or matching placebo. The proportion of subjects assigned to 210 mg or 140 mg in Cohort 2 will be determined by an unblinded interim analysis by an independent team will be conducted following after all subjects in Cohort 1 have been enrolled. Based on this unblinded interim analysis, the number of subjects to be allocated to 210 mg and/or 140 mg for Cohort 2 may be adjusted maintaining total number of subjects enrolled in the study at 40 according to the pre-specified decision criteria. Enrollment of Cohort 1 (210 mg or placebo) will be completed before enrollment of Cohort 2 (210 mg or 140 mg or placebo) is initiated. An additional 12 subjects (in an allocation ratio of 1 AMG 557: 1 placebo) may be enrolled into the study based on emerging PK and PD data, but will not exceed 210 mg.

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Diagnosis of SLE for at least 6 months as defined by the most recent American College of Rheumatology criteria, including a positive antinuclear antibodies (ANA) at screening or documented positive ANA (the titer should be at least 1:80) in the past;
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;
Currently taking methotrexate, azathioprine or mycophenolate mofetil for at least 12 weeks and at a stable dose for ≥ 4 weeks prior to randomization (other immunosuppressants including leflunomide are not allowed);
Other inclusion criteria may apply.

Exclusion Criteria:

Presence or history of vasculitis (compromising internal organs or extremities or leading to peripheral neuropathy), presence or history of active Central Nervous System (CNS) lupus (defined as seizure disorder, cerebral vascular accident, psychosis ascribed to SLE , encephalitis, meningitis, and myelitis), 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, or concomitant medications that would interfere with the study evaluation, completion, follow up, and/or procedures in the medical judgment of the investigator. This includes any age related co-morbidities such as congestive heart failure, angina, chronic obstructive pulmonary disease, asthma, and malignancies;
Use of any other over-the-counter or prescription medications within the 14 days or 5 half-lives (whichever is longer), prior to receiving the first dose of study medication. Acetaminophen (up to 2 g per day) for analgesia and hormone replacement therapy (eg, estrogen, thyroid) will be allowed. In addition, prescription drugs for hypertension or hypercholesterolemia, oral hypoglycemic drugs, or NSAIDs will be allowed. Other medications may be approved following review by the Principal Investigator and the Amgen Medical Monitor. Written documentation of this review and Amgen acknowledgment is required for subject participation;
Men and women of reproductive potential, unwilling to practice a highly effective method of birth control for the duration of the study and continuing for 9 months (men) and 6 months (women) after receiving the last dose of study drug. Highly effective methods of birth control include sexual abstinence (men, women); vasectomy or a condom with spermicide (men) in combination with either barrier methods, hormonal birth control or IUD (women);
Other exclusion criteria may apply.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01683695

Contacts

Contact: Amgen Call Center

866-572-6436

Locations

United States, California
Research Site	Recruiting
Los Angeles, California, United States, 90048
Research Site	Recruiting
San Leandro, California, United States, 94578
United States, Connecticut
Research Site	Recruiting
Danbury, Connecticut, United States, 06810
United States, New York
Research Site	Recruiting
Manhasset, New York, United States, 11030
Denmark
Research Site	Recruiting
Odense, Denmark, 5000
France
Research Site	Recruiting
Paris Cedex 13, France, 75651
Malaysia
Research Site	Recruiting
Ipoh, Perak, Malaysia, 30990
Research Site	Recruiting
Kuching, Sarawak, Malaysia, 93586
Research Site	Recruiting
Kuala Lumpur, Wilayah Persekutuan, Malaysia, 59100
Singapore
Research Site	Recruiting
Singapore, Singapore, 529889

Sponsors and Collaborators

Amgen

Investigators

Study Director:

MD

Amgen

More Information

Additional Information:

AmgenTrials clinical trials website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Amgen
ClinicalTrials.gov Identifier:	NCT01683695 History of Changes
Other Study ID Numbers:	20101103
Study First Received:	March 14, 2012
Last Updated:	April 23, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Amgen:

Lupus Arthritis, Systemic Lupus Erythematosus, AMG 557, Lupus

Additional relevant MeSH terms:

Arthritis
Lupus Erythematosus, Systemic
Joint Diseases
Musculoskeletal Diseases

Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on May 23, 2013