Safety and Efficacy of AMG 827 in Subjects With RA

• Sponsor: Amgen (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01059448
• Collaborator: (none)
• Enrollment: 211
• Locations: 44
• Arms: 4
• Actual Duration (Months): 10.1
• Patients Per Site: 4.8
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: AMG 827	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 211 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Long-Term Assessment of the Safety and Efficacy of AMG 827 Subcutaneous Treatment in Subjects With Rheumatoid Arthritis
• Actual Study Start Date: Jun 3, 2010
• Actual Primary Completion Date: Apr 5, 2011
• Actual Study Completion Date: Apr 5, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Placebo Q2WK / 210 mg AMG 827 Q2WK 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; AMG 827 210 mg
Experimental: 70 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK 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; AMG 827 210 mg
Experimental: 140mg AMG 827 Q2WK / 210mg AMG 827 Q2WK 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; AMG 827 210 mg
Experimental: 210 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK 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; AMG 827 210 mg

Outcome Measures

Primary Outcome Measures

1. Number of Participants With a Treatment-emergent Adverse Event (TEAE) [Day 1 to Week 52 of study 20090402]

   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.

2. Number of Participants Who Achieved an American College of Rheumatology (ACR) 20 Response [Baseline of parent study 20090061 to Week 2, 4, 8, 12, 16, 20, 24, 36 and 48 of study 20090402.]

   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.

3. Number of Participants Who Achieved an ACR 50 Response [Baseline of parent study 20090061 to Week 2, 4, 8, 12, 16, 20, 24, 36 and 48 of study 20090402.]

   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.

4. Number of Participants Who Achieved an ACR 70 Response [Baseline of parent study 20090061 to Week 2, 4, 8, 12, 16, 20, 24, 36 and 48 of study 20090402.]

   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.

5. Change From Baseline in Disease Activity Score 28 Joint (DAS28) Score [Baseline of parent study 20090061 to Week 2, 4, 8, 12, 16, 20, 24, 36 and 48 of study 20090402.]

   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.

6. Number of Participants With a DAS28 Score < 2.6 [Baseline of parent study 20090061 to Week 2, 4, 8, 12, 16, 20, 24, 36 and 48 of study 20090402.]

   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.

7. DAS28 Score at All Measured Timepoints [Baseline of parent study 20090061 to Week 2, 4, 8, 12, 16, 20, 24, 36 and 48 of study 20090402.]

   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.

8. CRP Levels at All Measured Timepoints [Baseline of parent study 20090061 to Week 2, 4, 8, 12, 16, 20, 24, 36 and 48 of study 20090402.]

   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.

9. ESR at All Measured Timepoints [Baseline of parent study 20090061 to Week 2, 4, 8, 12, 16, 20, 24, 36 and 48 of study 20090402.]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Scottsdale	Arizona	United States	85258
2	Research Site	Tucson	Arizona	United States	85711
3	Research Site	La Jolla	California	United States	92037
4	Research Site	Victorville	California	United States	92395
5	Research Site	Sarasota	Florida	United States	34239
6	Research Site	Rock Island	Illinois	United States	61201
7	Research Site	Springfield	Illinois	United States	62704
8	Research Site	Lexington	Kentucky	United States	40504
9	Research Site	Grand Rapids	Michigan	United States	49546
10	Research Site	Lansing	Michigan	United States	48910
11	Research Site	Freehold	New Jersey	United States	07728
12	Research Site	Portland	Oregon	United States	97239
13	Research Site	Duncansville	Pennsylvania	United States	16635
14	Research Site	Tacoma	Washington	United States	98405
15	Research Site	Sofia		Bulgaria	1612
16	Research Site	Sofia		Bulgaria	1709
17	Research Site	Veliko Tarnovo		Bulgaria	5000
18	Research Site	Winnipeg	Manitoba	Canada	R3N 0K6
19	Research Site	St. John's	Newfoundland and Labrador	Canada	A1A 5E8
20	Research Site	Toronto	Ontario	Canada	M5T 2S8
21	Research Site	Montreal	Quebec	Canada	H2L 1S6
22	Research Site	Praha 11		Czechia	148 00
23	Research Site	Praha 4		Czechia	140 59
24	Research Site	Bauska		Latvia	3901
25	Research Site	Daugavpils		Latvia	5417
26	Research Site	Liepaja		Latvia	3400
27	Research Site	Riga		Latvia	1002
28	Research Site	Riga		Latvia	1006
29	Research Site	Tijuana	Baja Calif	Mexico	22010
30	Research Site	Mexico City	Distrito F	Mexico	06700
31	Research Site	Mexico City	Distrito F	Mexico	14050
32	Research Site	Guadalajara	Jalisco	Mexico	44690
33	Research Site	Morelia	Michoacán	Mexico	58070
34	Research Site	San Luis Potosi	San Luis P	Mexico	78240
35	Research Site	Bialystok		Poland	15-351
36	Research Site	Bialystok		Poland	15-461
37	Research Site	Lublin		Poland	20-607
38	Research Site	Poznan		Poland	60-356
39	Research Site	ToruÅ"		Poland	87-100
40	Research Site	Warszawa		Poland	02-118
41	Research Site	Wroclaw		Poland	50-044
42	Research Site	Wroclaw		Poland	50-088
43	Research Site	Zyrardow		Poland	96-300
44	Research Site	Merseyside		United Kingdom	L49 5PE

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• AmgenTrials clinical trials website

Publications

None provided.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT01059448
• Other Study ID Numbers: 20090402
• First Posted: Feb 1, 2010
• Last Update Posted: Feb 28, 2022
• Last Verified: Jan 1, 2022

• Keywords provided by Amgen: Amgen; RA; AMG 827; 20090061
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Brodalumab

Study Results

Participant Flow

Recruitment Details

This was an open-label extension of study 20090061 (NCT00950989). Participants were required to complete the Week 16 visit of study 2009061, sign the informed consent form, complete all screening assessments, if applicable, and meet the safety-based eligibility criteria for study 20090402. 211 participants were enrolled across 45 centers in the United States, Canada, Czech Republic, Bulgaria, Latvia, Mexico, Poland, and the United Kingdom from 03 June 2010 to 18 May 2011.

Pre-assignment Detail

211 participants were enrolled and all 211 participants received study drug.

Arm/Group Title	Placebo Q2WK / 210 mg AMG 827 Q2WK	70 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK	140mg AMG 827 Q2WK / 210mg AMG 827 Q2WK	210 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK
Arm/Group Description	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.	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.	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.	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.
Period Title: Overall Study
STARTED	49	55	53	54
COMPLETED	0	0	0	0
NOT COMPLETED	49	55	53	54

Baseline Characteristics

Arm/Group Title	Placebo Q2WK / 210 mg AMG 827 Q2WK	70 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK	140mg AMG 827 Q2WK / 210mg AMG 827 Q2WK	210 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK	Total
Arm/Group Description	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.	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.	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.	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.	Total of all reporting groups
Overall Participants	49	55	53	54	211
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	49.9 (11.2)	52.6 (10.7)	54.6 (10.7)	51.6 (8.9)	52.2 (10.5)
Sex: Female, Male (Count of Participants)
Female	40 81.6%	43 78.2%	40 75.5%	44 81.5%	167 79.1%
Male	9 18.4%	12 21.8%	13 24.5%	10 18.5%	44 20.9%
Race (Count of Participants)
White or Caucasian	34 69.4%	45 81.8%	40 75.5%	47 87%	166 78.7%
Black or African American	1 2%	1 1.8%	1 1.9%	0 0%	3 1.4%
Hispanic or Latino	14 28.6%	8 14.5%	12 22.6%	6 11.1%	40 19%
Asian	0 0%	1 1.8%	0 0%	1 1.9%	2 0.9%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With a Treatment-emergent Adverse Event (TEAE)
Description	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.
Time Frame	Day 1 to Week 52 of study 20090402

Outcome Measure Data

Analysis Population Description

FAS - All analyzable participants who were treated with at least one dose of AMG 827.

Arm/Group Title	Placebo Q2WK / 210 mg AMG 827 Q2WK	70 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK	140mg AMG 827 Q2WK / 210mg AMG 827 Q2WK	210 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK
Arm/Group Description	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.	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.	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.	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.
Measure Participants	49	55	53	54
Count of Participants [Participants]	28 57.1%	32 58.2%	31 58.5%	32 59.3%

2. Primary Outcome

Title	Number of Participants Who Achieved an American College of Rheumatology (ACR) 20 Response
Description	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.
Time Frame	Baseline of parent study 20090061 to Week 2, 4, 8, 12, 16, 20, 24, 36 and 48 of study 20090402.

Outcome Measure Data

Analysis Population Description

FAS - All analyzable participants who were treated with at least one dose of AMG 827.

Arm/Group Title	Placebo Q2WK / 210 mg AMG 827 Q2WK	70 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK	140mg AMG 827 Q2WK / 210mg AMG 827 Q2WK	210 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK
Arm/Group Description	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.	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.	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.	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.
Measure Participants	47	54	53	52
20090402 Week 2	21 42.9%	24 43.6%	26 49.1%	24 44.4%
20090402 Week 4	27 55.1%	26 47.3%	24 45.3%	32 59.3%
20090402 Week 8	27 55.1%	31 56.4%	27 50.9%	29 53.7%
20090402 Week 12	25 51%	24 43.6%	23 43.4%	22 40.7%
20090402 Week 16	19 38.8%	28 50.9%	23 43.4%	22 40.7%
20090402 Week 20	19 38.8%	24 43.6%	15 28.3%	15 27.8%
20090402 Week 24	12 24.5%	17 30.9%	17 32.1%	12 22.2%
20090402 Week 36	7 14.3%	6 10.9%	5 9.4%	7 13%
20090402 Week 48	0 0%

3. Primary Outcome

Title	Number of Participants Who Achieved an ACR 50 Response
Description	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.
Time Frame	Baseline of parent study 20090061 to Week 2, 4, 8, 12, 16, 20, 24, 36 and 48 of study 20090402.

Outcome Measure Data

Analysis Population Description

FAS - All analyzable participants who were treated with at least one dose of AMG 827.

Arm/Group Title	Placebo Q2WK / 210 mg AMG 827 Q2WK	70 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK	140mg AMG 827 Q2WK / 210mg AMG 827 Q2WK	210 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK
Arm/Group Description	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.	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.	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.	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.
Measure Participants	47	54	53	52
20090402 Week 2	8 16.3%	8 14.5%	12 22.6%	7 13%
20090402 Week 4	8 16.3%	10 18.2%	10 18.9%	10 18.5%
20090402 Week 8	10 20.4%	9 16.4%	13 24.5%	11 20.4%
20090402 Week 12	13 26.5%	10 18.2%	10 18.9%	10 18.5%
20090402 Week 16	9 18.4%	7 12.7%	12 22.6%	11 20.4%
20090402 Week 20	9 18.4%	10 18.2%	5 9.4%	8 14.8%
20090402 Week 24	6 12.2%	6 10.9%	6 11.3%	9 16.7%
20090402 Week 36	4 8.2%	2 3.6%	2 3.8%	2 3.7%
20090402 Week 48	0 0%

4. Primary Outcome

Title	Number of Participants Who Achieved an ACR 70 Response
Description	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.
Time Frame	Baseline of parent study 20090061 to Week 2, 4, 8, 12, 16, 20, 24, 36 and 48 of study 20090402.

Outcome Measure Data

Analysis Population Description

FAS - All analyzable participants who were treated with at least one dose of AMG 827.

Arm/Group Title	Placebo Q2WK / 210 mg AMG 827 Q2WK	70 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK	140mg AMG 827 Q2WK / 210mg AMG 827 Q2WK	210 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK
Arm/Group Description	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.	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.	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.	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.
Measure Participants	49	54	53	52
20090402 Week 2	0 0%	4 7.3%	3 5.7%	2 3.7%
20090402 Week 4	2 4.1%	4 7.3%	3 5.7%	2 3.7%
20090402 Week 8	5 10.2%	4 7.3%	1 1.9%	4 7.4%
20090402 Week 12	5 10.2%	5 9.1%	2 3.8%	2 3.7%
20090402 Week 16	3 6.1%	3 5.5%	5 9.4%	5 9.3%
20090402 Week 20	4 8.2%	3 5.5%	1 1.9%	1 1.9%
20090402 Week 24	0 0%	2 3.6%	2 3.8%	6 11.1%
20090402 Week 36	0 0%	0 0%	1 1.9%	2 3.7%
20090402 Week 48	0 0%

5. Primary Outcome

Title	Change From Baseline in Disease Activity Score 28 Joint (DAS28) Score
Description	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.
Time Frame	Baseline of parent study 20090061 to Week 2, 4, 8, 12, 16, 20, 24, 36 and 48 of study 20090402.

Outcome Measure Data

Analysis Population Description

FAS - All analyzable participants who were treated with at least 1 dose of AMG 827.

Arm/Group Title	Placebo Q2WK / 210 mg AMG 827 Q2WK	70 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK	140mg AMG 827 Q2WK / 210mg AMG 827 Q2WK	210 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK
Arm/Group Description	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.	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.	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.	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.
Measure Participants	46	54	53	52
20090402 Week 2	-1.60 (1.02)	-1.39 (1.26)	-1.49 (1.22)	-1.31 (1.07)
20090402 Week 4	-1.60 (1.30)	-1.54 (1.32)	-1.40 (1.18)	-1.46 (1.08)
20090402 Week 8	-1.69 (1.32)	-1.65 (1.40)	-1.50 (1.12)	-1.64 (1.25)
20090402 Week 12	-1.99 (1.08)	-1.81 (1.29)	-1.38 (1.39)	-1.46 (1.15)
20090402 Week 16	-2.05 (1.27)	-1.71 (1.20)	-1.63 (1.37)	-1.53 (1.27)
20090402 Week 20	-1.94 (1.35)	-1.70 (1.26)	-1.61 (1.04)	-1.52 (1.21)
20090402 Week 24	-1.85 (1.00)	-1.66 (1.12)	-1.49 (1.21)	-1.99 (1.38)
20090402 Week 36	-1.87 (1.30)	-1.60 (1.01)	-1.61 (1.35)	-1.77 (1.46)
20090402 Week 48	0.18 (NA)

6. Primary Outcome

Title	Number of Participants With a DAS28 Score < 2.6
Description	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.
Time Frame	Baseline of parent study 20090061 to Week 2, 4, 8, 12, 16, 20, 24, 36 and 48 of study 20090402.

Outcome Measure Data

Analysis Population Description

FAS - All analyzable participants who were treated with at least one dose of AMG 827.

Arm/Group Title	Placebo Q2WK / 210 mg AMG 827 Q2WK	70 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK	140mg AMG 827 Q2WK / 210mg AMG 827 Q2WK	210 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK
Arm/Group Description	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.	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.	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.	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.
Measure Participants	49	55	53	54
Parent Study 20090061 Baseline	0 0%	0 0%	0 0%	0 0%
20090402 Baseline	2 4.1%	2 3.6%	0 0%	2 3.7%
20090402 Week 2	0 0%	3 5.5%	1 1.9%	1 1.9%
20090402 Week 4	1 2%	4 7.3%	1 1.9%	1 1.9%
20090402 Week 8	1 2%	3 5.5%	0 0%	5 9.3%
20090402 Week 12	2 4.1%	6 10.9%	0 0%	1 1.9%
20090402 Week 16	1 2%	4 7.3%	1 1.9%	5 9.3%
20090402 Week 20	1 2%	2 3.6%	1 1.9%	1 1.9%
20090402 Week 24	0 0%	1 1.8%	1 1.9%	2 3.7%
20090402 Week 36	0 0%	1 1.8%	1 1.9%	1 1.9%
20090402 Week 48	0 0%

7. Primary Outcome

Title	DAS28 Score at All Measured Timepoints
Description	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.
Time Frame	Baseline of parent study 20090061 to Week 2, 4, 8, 12, 16, 20, 24, 36 and 48 of study 20090402.

Outcome Measure Data

Analysis Population Description

FAS - All analyzable participants who were treated with at least one dose of AMG 827.

Arm/Group Title	Placebo Q2WK / 210 mg AMG 827 Q2WK	70 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK	140mg AMG 827 Q2WK / 210mg AMG 827 Q2WK	210 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK
Arm/Group Description	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.	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.	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.	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.
Measure Participants	49	55	53	54
Parent Study 20090061 Baseline	6.52 (0.85)	6.40 (0.78)	6.45 (0.81)	6.41 (0.72)
20090402 Baseline	5.16 (1.43)	5.22 (1.30)	5.33 (1.17)	5.49 (1.38)
20090402 Week 2	4.97 (1.22)	5.00 (1.32)	4.96 (1.30)	5.09 (1.27)
20090402 Week 4	5.00 (1.41)	4.87 (1.29)	5.06 (1.23)	4.96 (1.30)
20090402 Week 8	4.81 (1.34)	4.75 (1.33)	4.97 (1.23)	4.79 (1.48)
20090402 Week 12	4.64 (1.17)	4.59 (1.34)	5.13 (1.32)	5.02 (1.25)
20090402 Week 16	4.61 (1.23)	4.62 (1.17)	4.93 (1.38)	4.94 (1.49)
20090402 Week 20	4.58 (1.29)	4.52 (1.27)	4.73 (1.12)	4.98 (1.33)
20090402 Week 24	4.71 (1.08)	4.61 (1.13)	4.94 (1.19)	4.57 (1.61)
20090402 Week 36	4.66 (1.13)	4.54 (1.15)	5.06 (1.26)	4.90 (1.56)
20090402 Week 48	7.93 (NA)

8. Primary Outcome

Title	CRP Levels at All Measured Timepoints
Description	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.
Time Frame	Baseline of parent study 20090061 to Week 2, 4, 8, 12, 16, 20, 24, 36 and 48 of study 20090402.

Outcome Measure Data

Analysis Population Description

FAS - All analyzable participants who were treated with at least one dose of AMG 827.

Arm/Group Title	Placebo Q2WK / 210 mg AMG 827 Q2WK	70 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK	140mg AMG 827 Q2WK / 210mg AMG 827 Q2WK	210 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK
Arm/Group Description	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.	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.	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.	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.
Measure Participants	49	55	53	54
Parent Study 20090061 Baseline	12.95 (11.99)	14.74 (17.50)	18.91 (24.35)	12.22 (10.69)
20090402 Baseline	11.42 (12.13)	12.23 (12.75)	14.48 (18.84)	12.25 (12.49)
20090402 Week 2	9.67 (8.91)	10.44 (10.31)	18.58 (28.49)	10.56 (11.04)
20090402 Week 4	10.70 (10.05)	12.79 (15.91)	14.46 (15.39)	11.47 (11.67)
20090402 Week 8	9.18 (10.51)	12.19 (14.18)	13.84 (15.62)	13.20 (15.11)
20090402 Week 12	9.07 (9.38)	12.61 (14.61)	15.68 (14.82)	14.54 (13.25)
20090402 Week 16	12.09 (12.69)	12.91 (20.22)	16.01 (17.40)	12.92 (11.70)
20090402 Week 20	10.21 (12.13)	10.59 (12.05)	14.14 (16.69)	14.79 (18.38)
20090402 Week 24	7.99 (5.82)	8.76 (9.16)	16.50 (21.01)	9.41 (10.04)
20090402 Week 36	8.49 (9.96)	9.92 (12.22)	12.02 (17.38)	8.89 (8.71)
20090402 Week 48	22.10 (NA)

9. Primary Outcome

Title	ESR at All Measured Timepoints
Description	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.
Time Frame	Baseline of parent study 20090061 to Week 2, 4, 8, 12, 16, 20, 24, 36 and 48 of study 20090402.

Outcome Measure Data

Analysis Population Description

FAS - All analyzable participants who were treated with at least one dose of AMG 827.

Arm/Group Title	Placebo Q2WK / 210 mg AMG 827 Q2WK	70 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK	140mg AMG 827 Q2WK / 210mg AMG 827 Q2WK	210 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK
Arm/Group Description	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.	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.	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.	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.
Measure Participants	49	55	53	54
Parent Study 20090061 Baseline	50.12 (20.53)	44.27 (18.72)	45.81 (21.97)	45.06 (20.03)
20090402 Baseline	38.35 (27.78)	38.15 (23.79)	41.89 (22.27)	39.15 (24.70)
20090402 Week 2	36.78 (21.43)	36.83 (27.11)	37.65 (19.24)	37.00 (25.23)
20090402 Week 4	39.27 (23.73)	36.07 (21.44)	40.53 (23.50)	38.31 (24.70)
20090402 Week 8	37.40 (23.26)	34.65 (23.14)	38.43 (19.50)	35.55 (23.52)
20090402 Week 12	36.31 (18.30)	36.09 (24.30)	42.28 (22.74)	39.30 (22.54)
20090402 Week 16	38.21 (23.08)	40.27 (26.07)	43.78 (23.23)	39.43 (22.81)
20090402 Week 20	43.41 (28.27)	35.16 (24.73)	38.00 (26.25)	40.48 (26.71)
20090402 Week 24	42.83 (25.05)	41.07 (23.14)	40.58 (21.12)	42.62 (27.23)
20090402 Week 36	36.62 (16.19)	38.69 (23.22)	36.85 (18.07)	38.07 (26.39)
20090402 Week 48	65.00 (NA)

Adverse Events

Time Frame	From first dose of study drug in 20090402 until the end of study (maximum duration was 366 days)
Arm/Group Title	Placebo / AMG 827 210 mg Q2WK		70 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK		140mg AMG 827 Q2WK / 210mg AMG 827 Q2WK		210 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK
Arm/Group Description	Participants who were administered matching placebo in parent study 2009061 and were administered 210 mg subcutaneous (SC) AMG 827 at Day 1, Week 1, Week 2, and every other week thereafter (Q2WK). Participants also received weekly intramuscular, oral or SC doses of methotrexate.		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.		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.		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.
All Cause Mortality
	Placebo / AMG 827 210 mg Q2WK		70 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK		140mg AMG 827 Q2WK / 210mg AMG 827 Q2WK		210 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo / AMG 827 210 mg Q2WK		70 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK		140mg AMG 827 Q2WK / 210mg AMG 827 Q2WK		210 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/49 (4.1%)		5/55 (9.1%)		1/53 (1.9%)		0/54 (0%)
Gastrointestinal disorders
Dysphagia	0/49 (0%)		1/55 (1.8%)		0/53 (0%)		0/54 (0%)
Gastritis	0/49 (0%)		1/55 (1.8%)		0/53 (0%)		0/54 (0%)
Oesophageal achalasia	0/49 (0%)		1/55 (1.8%)		0/53 (0%)		0/54 (0%)
General disorders
Chest pain	1/49 (2%)		0/55 (0%)		0/53 (0%)		0/54 (0%)
Hepatobiliary disorders
Cholelithiasis	0/49 (0%)		1/55 (1.8%)		0/53 (0%)		0/54 (0%)
Immune system disorders
Hypersensitivity	1/49 (2%)		0/55 (0%)		0/53 (0%)		0/54 (0%)
Infections and infestations
Pneumonia	1/49 (2%)		0/55 (0%)		0/53 (0%)		0/54 (0%)
Injury, poisoning and procedural complications
Traumatic brain injury	0/49 (0%)		1/55 (1.8%)		0/53 (0%)		0/54 (0%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	0/49 (0%)		0/55 (0%)		1/53 (1.9%)		0/54 (0%)
Psychiatric disorders
Completed suicide	0/49 (0%)		1/55 (1.8%)		0/53 (0%)		0/54 (0%)
Renal and urinary disorders
Nephrotic syndrome	0/49 (0%)		1/55 (1.8%)		0/53 (0%)		0/54 (0%)
Other (Not Including Serious) Adverse Events
	Placebo / AMG 827 210 mg Q2WK		70 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK		140mg AMG 827 Q2WK / 210mg AMG 827 Q2WK		210 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/49 (30.6%)		18/55 (32.7%)		19/53 (35.8%)		22/54 (40.7%)
Ear and labyrinth disorders
Vertigo	0/49 (0%)		1/55 (1.8%)		1/53 (1.9%)		3/54 (5.6%)
Eye disorders
Conjunctivitis	0/49 (0%)		3/55 (5.5%)		0/53 (0%)		1/54 (1.9%)
Gastrointestinal disorders
Gastritis	0/49 (0%)		4/55 (7.3%)		1/53 (1.9%)		0/54 (0%)
Nausea	1/49 (2%)		1/55 (1.8%)		0/53 (0%)		3/54 (5.6%)
General disorders
Injection site pain	5/49 (10.2%)		1/55 (1.8%)		2/53 (3.8%)		3/54 (5.6%)
Infections and infestations
Nasopharyngitis	1/49 (2%)		4/55 (7.3%)		4/53 (7.5%)		2/54 (3.7%)
Upper respiratory tract infection	5/49 (10.2%)		3/55 (5.5%)		7/53 (13.2%)		4/54 (7.4%)
Urinary tract infection	1/49 (2%)		1/55 (1.8%)		1/53 (1.9%)		3/54 (5.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	4/49 (8.2%)		3/55 (5.5%)		2/53 (3.8%)		3/54 (5.6%)
Back pain	0/49 (0%)		1/55 (1.8%)		3/53 (5.7%)		0/54 (0%)
Rheumatoid arthritis	2/49 (4.1%)		3/55 (5.5%)		4/53 (7.5%)		3/54 (5.6%)
Nervous system disorders
Headache	1/49 (2%)		4/55 (7.3%)		3/53 (5.7%)		2/54 (3.7%)

Limitations/Caveats

The study was terminated on 18 May 2011 because AMG 827 was not shown to be efficacious in the parent study (Study 20090061) when compared to placebo at any dose as measured by ACR 20, 50, or 70 responses. In addition, there was no observed difference compared to placebo in responses as measured by the individual components of the ACR response criteria.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.