Safety and Efficacy of AMG 827 in Subjects With RA

NCT01059448 | Terminated Phase 2 Results

• 1 other identifier: 20090402
• Study Type: interventional
• Target: 211
• Locations: 8 countries
• Sites: 44

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.

Conditions

Rheumatoid Arthritis

Keywords

Amgen; RA; AMG 827; 20090061

Outcome Measures

Primary Outcomes (9)

• 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.

Study Arms (4)

Placebo Q2WK / 210 mg AMG 827 Q2WK

EXPERIMENTAL

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

70 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK

EXPERIMENTAL

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

140mg AMG 827 Q2WK / 210mg AMG 827 Q2WK

EXPERIMENTAL

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

210 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK

EXPERIMENTAL

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

Interventions

AMG 827 DRUG

AMG 827 210 mg

140mg AMG 827 Q2WK / 210mg AMG 827 Q2WK; 210 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK; 70 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK; Placebo Q2WK / 210 mg AMG 827 Q2WK

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (44)

Research Site

Scottsdale, Arizona, 85258, United States

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Tucson, Arizona, 85711, United States

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La Jolla, California, 92037, United States

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Victorville, California, 92395, United States

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Sarasota, Florida, 34239, United States

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Rock Island, Illinois, 61201, United States

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Springfield, Illinois, 62704, United States

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Lexington, Kentucky, 40504, United States

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Grand Rapids, Michigan, 49546, United States

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Lansing, Michigan, 48910, United States

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Freehold, New Jersey, 07728, United States

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Portland, Oregon, 97239, United States

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Duncansville, Pennsylvania, 16635, United States

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Tacoma, Washington, 98405, United States

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Sofia, 1612, Bulgaria

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Sofia, 1709, Bulgaria

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Veliko Tarnovo, 5000, Bulgaria

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Winnipeg, Manitoba, R3N 0K6, Canada

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St. John's, Newfoundland and Labrador, A1A 5E8, Canada

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Toronto, Ontario, M5T 2S8, Canada

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Montreal, Quebec, H2L 1S6, Canada

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Prague, 140 59, Czechia

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Prague, 148 00, Czechia

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Bauska, 3901, Latvia

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Daugavpils, 5417, Latvia

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Liepāja, 3400, Latvia

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Riga, 1002, Latvia

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Riga, 1006, Latvia

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Tijuana, Baja Calif, 22010, Mexico

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Mexico City, Distrito F, 06700, Mexico

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Mexico City, Distrito F, 14050, Mexico

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Guadalajara, Jalisco, 44690, Mexico

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Morelia, Michoacán, 58070, Mexico

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San Luis Potosí City, San Luis P, 78240, Mexico

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Bialystok, 15-351, Poland

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Bialystok, 15-461, Poland

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Lublin, 20-607, Poland

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Poznan, 60-356, Poland

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ToruÅ", 87-100, Poland

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Warsaw, 02-118, Poland

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Wroclaw, 50-044, Poland

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Wroclaw, 50-088, Poland

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Żyrardów, 96-300, Poland

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Merseyside, L49 5PE, United Kingdom

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Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

brodalumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Limitations and 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.

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2010
• First Posted: February 1, 2010
• Study Start: June 3, 2010
• Primary Completion: April 5, 2011
• Study Completion: April 5, 2011
• Last Updated: February 28, 2022
• Results First Posted: February 28, 2022

Record last verified: 2022-01

Locations

US (14); CA (4); ME (6); GB (1); PL (9); LA (5); BU (3); CZ (2)