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Safety and Efficacy of AMG 827 in Subjects With RA

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01059448
Recruitment Status : Terminated (Lack of efficacy for Brodalumab in Rheumatoid Arthritis (RA))
First Posted : February 1, 2010
Results First Posted : February 28, 2022
Last Update Posted : February 28, 2022
Sponsor:
Information provided by (Responsible Party):
Amgen

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

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Study Type : Interventional  (Clinical Trial)
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 : June 3, 2010
Actual Primary Completion Date : April 5, 2011
Actual Study Completion Date : April 5, 2011

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Number of Participants With a Treatment-emergent Adverse Event (TEAE) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01059448


Locations
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United States, Arizona
Research Site
Scottsdale, Arizona, United States, 85258
Research Site
Tucson, Arizona, United States, 85711
United States, California
Research Site
La Jolla, California, United States, 92037
Research Site
Victorville, California, United States, 92395
United States, Florida
Research Site
Sarasota, Florida, United States, 34239
United States, Illinois
Research Site
Rock Island, Illinois, United States, 61201
Research Site
Springfield, Illinois, United States, 62704
United States, Kentucky
Research Site
Lexington, Kentucky, United States, 40504
United States, Michigan
Research Site
Grand Rapids, Michigan, United States, 49546
Research Site
Lansing, Michigan, United States, 48910
United States, New Jersey
Research Site
Freehold, New Jersey, United States, 07728
United States, Oregon
Research Site
Portland, Oregon, United States, 97239
United States, Pennsylvania
Research Site
Duncansville, Pennsylvania, United States, 16635
United States, Washington
Research Site
Tacoma, Washington, United States, 98405
Bulgaria
Research Site
Sofia, Bulgaria, 1612
Research Site
Sofia, Bulgaria, 1709
Research Site
Veliko Tarnovo, Bulgaria, 5000
Canada, Manitoba
Research Site
Winnipeg, Manitoba, Canada, R3N 0K6
Canada, Newfoundland and Labrador
Research Site
St. John's, Newfoundland and Labrador, Canada, A1A 5E8
Canada, Ontario
Research Site
Toronto, Ontario, Canada, M5T 2S8
Canada, Quebec
Research Site
Montreal, Quebec, Canada, H2L 1S6
Czechia
Research Site
Praha 11, Czechia, 148 00
Research Site
Praha 4, Czechia, 140 59
Latvia
Research Site
Bauska, Latvia, 3901
Research Site
Daugavpils, Latvia, 5417
Research Site
Liepaja, Latvia, 3400
Research Site
Riga, Latvia, 1002
Research Site
Riga, Latvia, 1006
Mexico
Research Site
Tijuana, Baja Calif, Mexico, 22010
Research Site
Mexico City, Distrito F, Mexico, 06700
Research Site
Mexico City, Distrito F, Mexico, 14050
Research Site
Guadalajara, Jalisco, Mexico, 44690
Research Site
Morelia, Michoacán, Mexico, 58070
Research Site
San Luis Potosi, San Luis P, Mexico, 78240
Poland
Research Site
Bialystok, Poland, 15-351
Research Site
Bialystok, Poland, 15-461
Research Site
Lublin, Poland, 20-607
Research Site
Poznan, Poland, 60-356
Research Site
ToruÅ", Poland, 87-100
Research Site
Warszawa, Poland, 02-118
Research Site
Wroclaw, Poland, 50-044
Research Site
Wroclaw, Poland, 50-088
Research Site
Zyrardow, Poland, 96-300
United Kingdom
Research Site
Merseyside, United Kingdom, L49 5PE
Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen
Additional Information:
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01059448    
Other Study ID Numbers: 20090402
First Posted: February 1, 2010    Key Record Dates
Results First Posted: February 28, 2022
Last Update Posted: February 28, 2022
Last Verified: January 2022
Keywords provided by Amgen:
Amgen
RA
AMG 827
20090061
Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Brodalumab
Dermatologic Agents