Safety and Efficacy of AMG 827 in Subjects With RA

Study Overview
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Brief Summary
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This is an extension study for subjects who participated in Protocol 20090061 (NCT00950989). All subjects in this study will receive a 210mg injection of AMG827 for treatment for their Rheumatoid Arthritis for up to 5 years.

Official Title
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A Long-Term Assessment of the Safety and Efficacy of AMG 827 Subcutaneous Treatment in Subjects With Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: AMG 827


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has provided informed consent. Subject was randomized into study 20090061 and completed the week 16 evaluation. Negative test for hepatitis B virus (HBV) surface antigen, hepatitis C virus (HCV) antibody, and/or human immunodeficiency virus (HIV) in subjects if clinically indicated (eg, known recent exposure) in the opinion of the investigator. Subject must test negative for Tuberculosis. Exclusion Criteria: Subject had any SAE reported during 20090061 that was considered to be related to IP. Subject is currently experiencing an infection of CTCAE grade 2 (if requiring oral antibiotics) or higher. Subject is ineligible until the infection is resolved in the opinion of the investigator. For subjects with > 4 weeks between the week 16 visit of 20090061 and the planned first IP dose in 20090402, subject has laboratory abnormalities at screening, including: Elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT); >1.5x upper limit of normal) Serum total bilirubin ≥1.5 mg/dL Hemoglobin < 11 g/dL Platelet count < 125,000 /mm3 White blood cell count < 3,000 cells/mm3 Absolute neutrophil count < 2000/mm3 Estimated creatinine clearance < 50 mL/min (Cockroft-Gault formula, central lab will calculate value and provide to sites) Subject has a significant concurrent medical conditions, including: Type 1 diabetes Poorly controlled type 2 diabetes (Hemoglobin A1c > 8.5) Symptomatic heart failure (New York Heart Association class II, III, or IV) Myocardial infarction within the last year Current or history of unstable angina pectoris within the last year Uncontrolled hypertension as defined by resting blood pressure > 150/90 mmHg prior to first IP dose (confirmed by a repeat assessment) Severe chronic pulmonary disease (eg, requiring oxygen therapy) Major chronic inflammatory disease or connective tissue disease other than rheumatoid arthritis (eg, systemic lupus erythematosus), with the exception of secondary Sjögren's syndrome Multiple sclerosis or any other demyelinating disease Active malignancy, including evidence of cutaneous basal or squamous cell carcinoma or melanoma, or history of cancer (except successfully treated in situ cervical cancer or squamous or basal cell carcinoma of the skin) Any condition that, in the opinion of the investigator, might cause this study to be detrimental to the subject Subject is pregnant or breast feeding, or planning to become pregnant while enrolled in the study, up to the subject's last study visit including the follow-up period. Female subject is not willing to abstain from sexual intercourse or use 2 highly effective forms of birth control for the duration of the study and at least 40 days after the last dose (except women at least 3 years postmenopausal or surgically sterile). Highly effective methods of birth control for women include but are not limited to birth control pills, Depo Provera® injections, contraceptive implants, or occlusive cap (barrier method) in combination with barrier methods used by the man. Male subject is not willing to abstain from sexual intercourse or use 2 highly effective forms of birth control for the duration of the study, plus an additional 16 weeks after the last dose (except for men who are surgically sterile or whose female partners are at least 3 years postmenopausal or surgically sterile). Highly effective methods of birth control include but are not limited to a condom in combination with hormonal birth control or barrier methods used by the woman. Male subject (including vasectomised males) with a pregnant female partner is not willing to use effective methods to ensure that an unborn child is not exposed to AMG 827 via semen. Effective methods to ensure that an unborn child is not exposed to AMG 827 via semen include condoms or abstinence. Subject has used any of the following within 14 days prior to IP initiation Non-biologic disease-modifying anti-rheumatic drugs (DMARD) other than as allowed in 20090061 Intra-articular, intramuscular, or intravenous corticosteroids, including adrenocorticotropic hormone Subject has used any of the following within 3 months prior to IP initiation Leflunomide Live vaccines Commercially available or experimental biologic DMARD except for AMG 827 Subject has received gold therapy within 6 months prior to IP initiation. Subject received another investigational agent (other than AMG 827) or participated in an investigational device study subsequent to 20090061. Other investigational procedures are excluded.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Placebo Q2WK / 210 mg AMG 827 Q2WK<br>Participants who were administered matching placebo in parent study 20090061 and were administered 210 mg subcutaneous (SC) AMG 827 at Day 1, Week 1, Week 2, and every other week thereafter (Q2WK). Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate. | Drug: AMG 827<br>* AMG 827 210 mg<br>|
| Experimental: 70 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK<br>Participants who were administered 70 mg AMG 827 in parent study 20090061 and were administered 210 mg SC AMG 827 at Day 1, Week 1, Week 2 and Q2WK thereafter. Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate. | Drug: AMG 827<br>* AMG 827 210 mg<br>|
| Experimental: 140mg AMG 827 Q2WK / 210mg AMG 827 Q2WK<br>Participants who were administered 140 mg AMG 827 in parent study 20090061 and were administered 210 mg SC AMG 827 at Day 1, Week 1, Week 2, and Q2WK thereafter. Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate. | Drug: AMG 827<br>* AMG 827 210 mg<br>|
| Experimental: 210 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK<br>Participants who were administered 210 mg AMG 827 in parent study 20090061 and were administered 210 mg SC AMG 827 at Day 1, Week 1, Week 2, and Q2WK thereafter. Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate. | Drug: AMG 827<br>* AMG 827 210 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Treatment-emergent Adverse Event (TEAE) | A TEAE was defined as an event that occurred after the first dose date and before the end of study date in study 20090402; or an event that was already present prior to the initiation of the investigational product (i.e. present at study 20090402) baseline but worsened in either frequency or severity after the first dose date and before the end of study date in study 20090402. TEAEs also included serious treatment-emergent adverse events and clinically significant changes from baseline in hematology, chemistry and urinalysis profiles and clinically significant changes in vital sign measurements. | Day 1 to Week 52 of study 20090402 | 
| Number of Participants Who Achieved an American College of Rheumatology (ACR) 20 Response | An ACR 20 response was defined as at least a 20% improvement from baseline in both tender/painful and swollen joint counts, and a 20% improvement or more in at least 3 of the following 5 criteria: physician global assessment of disease activity (PGA), subject global assessment of disease activity (SGA), participant global assessment of joint pain, participant self-assessment of disability (Health Assessment Questionnaire, HAQ-DI), and acute phase reactant: erythrocyte sedimentation rate (ESR) or C-Reactive Protein (CRP), whichever had a bigger improvement. Participants were excluded from analysis if an ACR 20 response could not be determined due to missing component data. Baseline refers to the baseline in parent study 20090061. | Baseline of parent study 20090061 to Week 2, 4, 8, 12, 16, 20, 24, 36 and 48 of study 20090402. | 
| Number of Participants Who Achieved an ACR 50 Response | An ACR 50 response was defined as at least a 50% improvement from baseline in both tender/painful and swollen joint counts, and a 50% improvement or more in at least 3 of the following 5 criteria: PGA, SGA, participant global assessment of joint pain, participant self-assessment of disability (HAQ-DI), and acute phase reactant: ESR or CRP, whichever had a bigger improvement. Participants were excluded from analysis if an ACR 50 response could not be determined due to missing component data. Baseline refers to the baseline in parent study 20090061. | Baseline of parent study 20090061 to Week 2, 4, 8, 12, 16, 20, 24, 36 and 48 of study 20090402. | 
| Number of Participants Who Achieved an ACR 70 Response | An ACR 70 response was defined as at least a 70% improvement from baseline in both tender/painful and swollen joint counts, and a 70% improvement or more in at least 3 of the following 5 criteria: PGA, SGA, participant global assessment of joint pain, participant self-assessment of disability (HAQ-DI), and acute phase reactant: ESR or CRP, whichever had a bigger improvement. Participants were excluded from analysis if an ACR 70 response could not be determined due to missing component data. Baseline refers to the baseline in parent study 20090061. | Baseline of parent study 20090061 to Week 2, 4, 8, 12, 16, 20, 24, 36 and 48 of study 20090402. | 
| Change From Baseline in Disease Activity Score 28 Joint (DAS28) Score | The DAS28 is a composite score that is based on a 28-joint count (using 28 tender and 28 swollen joints), ESR, and SGA. The following formula was used where T/P28 and SW28 represent the tender and swollen 28 joint counts, respectively. The 28 joint counts include 10 proximal interphalangeal, 10 metacarpophalangeal, 2 wrist, 2 elbow, 2 shoulder, and 2 knee joints. DAS28 = 0.56 √T/P28 + 0.28 √SW28 + 0.7 x ln (ESR) +0.014 x SGA. DAS28 score ranged from 0 to 10, where a higher score represented higher disease activity. A negative change from baseline indicated a reduction in disease activity. Baseline refers to the baseline in parent study 20090061. | Baseline of parent study 20090061 to Week 2, 4, 8, 12, 16, 20, 24, 36 and 48 of study 20090402. | 
| Number of Participants With a DAS28 Score < 2.6 | The DAS28 is a composite score that is based on a 28-joint count (using 28 tender and 28 swollen joints), ESR, and SGA. The following formula was used where T/P28 and SW28 represent the tender and swollen 28 joint counts, respectively. The 28 joint counts include 10 proximal interphalangeal, 10 metacarpophalangeal, 2 wrist, 2 elbow, 2 shoulder, and 2 knee joints. DAS28 = 0.56 √T/P28 + 0.28 √SW28 + 0.7 x ln (ESR) +0.014 x SGA. DAS28 score ranged from 0 to 10, where a higher score represented higher disease activity. A score of <2.6 indicated disease activity remission. 1 participant in the Arm Placebo Q2WK / 210 mg AMG 827 Q2WK was missing baseline data for DAS28. | Baseline of parent study 20090061 to Week 2, 4, 8, 12, 16, 20, 24, 36 and 48 of study 20090402. | 
| DAS28 Score at All Measured Timepoints | The DAS28 is a composite score that is based on a 28-joint count (using 28 tender and 28 swollen joints), ESR, and SGA. The following formula was used where T/P28 and SW28 represent the tender and swollen 28 joint counts, respectively. The 28 joint counts include 10 proximal interphalangeal, 10 metacarpophalangeal, 2 wrist, 2 elbow, 2 shoulder, and 2 knee joints. DAS28 = 0.56 √T/P28 + 0.28 √SW28 + 0.7 x ln (ESR) +0.014 x SGA. DAS28 score ranged from 0 to 10, where a higher score represented higher disease activity. 1 participant in the Arm Placebo Q2WK / 210 mg AMG 827 Q2WK was missing baseline data for DAS28. | Baseline of parent study 20090061 to Week 2, 4, 8, 12, 16, 20, 24, 36 and 48 of study 20090402. | 
| CRP Levels at All Measured Timepoints | All blood samples were taken before the dose of IP was administered. Blood samples were processed and sent to the central laboratory. The central laboratory were responsible for completing assessments. | Baseline of parent study 20090061 to Week 2, 4, 8, 12, 16, 20, 24, 36 and 48 of study 20090402. | 
| ESR at All Measured Timepoints | All blood samples were taken before the dose of IP was administered. ESR was performed locally at each site and the ESR data was submitted to the central laboratory. | Baseline of parent study 20090061 to Week 2, 4, 8, 12, 16, 20, 24, 36 and 48 of study 20090402. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amgen, RA, AMG 827, 20090061