Back to resultsBrodalumab (AMG 827) in Rheumatoid Arthritis (RA) Participants With Inadequate Response to Methotrexate
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Brodalumab
Placebo
Methotrexate
folic acid
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Autoimmune Diseases, Musculoskeletal Diseases, Joint Diseases, Arthritis, Connective Tissue Diseases, Arthritis, Rheumatoid, Rheumatic Diseases
Eligibility Criteria
Inclusion Criteria:
- Active RA for least 6 months
- Current RA defined as ≥ 6 swollen joints (out of 66 joints examined) and ≥ 8 tender/painful joints (out of 68 joints examined) at screening and baseline (swollen and tender/painful joint count must not include distal interphalangeal joints) and at least 1 of the following at screening: Erythrocyte sedimentation rate ≥ 28 mm or C-reactive protein > 15 mg/L
- At least 1 of the following at screening: Rheumatoid factor positive or Anti-cyclic citrullinated peptide antibody positive
- Currently taking methotrexate for ≥ 12 weeks and on a stable dose of methotrexate at 15 to 25 mg weekly for ≥ 4 weeks at day -1.
Exclusion Criteria:
- Prosthetic joint infection within 5 years of screening or native joint infection within 1 year of screening
- Class IV RA
- Felty's syndrome
- Presence of serious infection
- Significant concurrent medical conditions
- Pregnant or breast feeding
- Significant Laboratory abnormalities
- Any disease-modifying anti-rheumatic drug (DMARD) other than methotrexate within 28 days
- Leflunomide or live vaccines within 3 months
- Previous use of any experimental or commercially available biologic DMARD
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Placebo Comparator
Experimental
Experimental
Placebo Comparator
Arm Label
Placebo
Brodalumab 70 mg
Brodalumab 140 mg
Brodalumab 210 mg
Arm Description
Placebo on day 1 and weeks 1, 2, 4, 6, 8, and 10 for a total of 7 doses plus a stable weekly dose of methotrexate and folic acid supplementation (at least 5 mg per week).
70 mg brodalumab on day 1 and weeks 1, 2, 4, 6, 8, and 10 for a total of 7 doses plus a stable weekly dose of methotrexate and folic acid supplementation (at least 5 mg per week).
140 mg brodalumab on day 1 and weeks 1, 2, 4, 6, 8, and 10 for a total of 7 doses plus a stable weekly dose of methotrexateand folic acid supplementation (at least 5 mg per week).
210 mg brodalumab on day 1 and weeks 1, 2, 4, 6, 8, and 10 for a total of 7 doses plus a stable weekly dose of methotrexate and folic acid supplementation (at least 5 mg per week).
Outcomes
Primary Outcome Measures
Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12
A positive ACR50 response is defined if the following 3 criteria for improvement from baseline were met:
50% improvement in 68 tender joint count;
50% improvement in 66 swollen joint count; and
50% improvement in at least 3 of the 5 following parameters:
Patient's assessment of joint pain (measured on a 100 mm visual analog scale [VAS]),
Patient's global assessment of disease activity (measured on a 0-10 Likert scale),
Physician's global assessment of disease activity (measured on a 0-10 Likert scale),
Patient's self assessment of disability (Health Assessment Questionnaire - Disability Index [HAQ-DI]),
Acute phase reactant: erythrocyte sedimentation rate (ESR) or C-Reactive Protein (CRP), whichever has bigger improvement.
Secondary Outcome Measures
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12
A positive ACR20 response is defined if the following 3 criteria for improvement from baseline were met:
20% improvement in 68 tender joint count;
20% improvement in 66 swollen joint count; and
20% improvement in at least 3 of the 5 following parameters:
Patient's assessment of joint pain (measured on a 100 mm visual analog scale [VAS]),
Patient's global assessment of disease activity (measured on a 0-10 Likert scale),
Physician's global assessment of disease activity (measured on a 0-10 Likert scale),
Patient's self assessment of disability (Health Assessment Questionnaire - Disability Index [HAQ-DI]),
Acute phase reactant: erythrocyte sedimentation rate (ESR) or C-Reactive Protein (CRP), whichever has bigger improvement.
Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12
A positive ACR70 response is defined if the following 3 criteria for improvement from baseline were met:
70% improvement in 68 tender joint count;
70% improvement in 66 swollen joint count; and
70% improvement in at least 3 of the 5 following parameters:
Patient's assessment of joint pain (measured on a 100 mm visual analog scale [VAS]),
Patient's global assessment of disease activity (measured on a 0-10 Likert scale),
Physician's global assessment of disease activity (measured on a 0-10 Likert scale),
Patient's self assessment of disability (Health Assessment Questionnaire - Disability Index [HAQ-DI]),
Acute phase reactant: erythrocyte sedimentation rate (ESR) or C-Reactive Protein (CRP), whichever has bigger improvement.
Disease Activity Score 28 (DAS28) at Week 12
The DAS28 is a composite score to measure disease activity in patients with rheumatoid arthritis, derived from the following variables: • The number of tender joints assessed using the 28-jount count and number of swollen joints assessed using the 28-joint count; • Erythrocyte sedimentation rate (ESR); • Patient's global assessment of disease activity (measured on a 0-10 Likert scale). The DAS28 score ranges from 0 to 10, with higher scores indicating more severe disease activity.
Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation
AEs are defined as any untoward medical occurrence, that does not necessarily have a causal relationship with this treatment. SAEs are defined as an AE that: is fatal; is life threatening (places the subject at immediate risk of death); requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; other significant medical hazard. The severity of events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v 4.0: mild=grade 1, moderate=grade 2, severe=grade 3, life-threatening=grade 4, death=grade 5.
Pharmacokinetics (PK) of Brodalumab: Maximum Observed Concentration (Cmax)
PK of Brodalumab: Time to Maximum Observed Concentration (Tmax)
PK of Brodalumab: Area Under the Curve During the Dosing Interval (AUCtau)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00950989
Brief Title
Brodalumab (AMG 827) in Rheumatoid Arthritis (RA) Participants With Inadequate Response to Methotrexate
Official Title
A Randomized, Double-blind, Placebo-controlled, Multiple-dose Study to Evaluate the Safety, Tolerability, and Efficacy of AMG 827 in Subjects With Rheumatoid Arthritis and an Inadequate Response to Methotrexate
Study Type
Interventional
2. Study Status
Record Verification Date
November 2021
Overall Recruitment Status
Completed
Study Start Date
December 30, 2009 (Actual)
Primary Completion Date
February 11, 2011 (Actual)
Study Completion Date
February 11, 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
5. Study Description
Brief Summary
Study in participants with RA who have an inadequate response to methotrexate.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
Autoimmune Diseases, Musculoskeletal Diseases, Joint Diseases, Arthritis, Connective Tissue Diseases, Arthritis, Rheumatoid, Rheumatic Diseases
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
252 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo on day 1 and weeks 1, 2, 4, 6, 8, and 10 for a total of 7 doses plus a stable weekly dose of methotrexate and folic acid supplementation (at least 5 mg per week).
Arm Title
Brodalumab 70 mg
Arm Type
Experimental
Arm Description
70 mg brodalumab on day 1 and weeks 1, 2, 4, 6, 8, and 10 for a total of 7 doses plus a stable weekly dose of methotrexate and folic acid supplementation (at least 5 mg per week).
Arm Title
Brodalumab 140 mg
Arm Type
Experimental
Arm Description
140 mg brodalumab on day 1 and weeks 1, 2, 4, 6, 8, and 10 for a total of 7 doses plus a stable weekly dose of methotrexateand folic acid supplementation (at least 5 mg per week).
Arm Title
Brodalumab 210 mg
Arm Type
Placebo Comparator
Arm Description
210 mg brodalumab on day 1 and weeks 1, 2, 4, 6, 8, and 10 for a total of 7 doses plus a stable weekly dose of methotrexate and folic acid supplementation (at least 5 mg per week).
Intervention Type
Drug
Intervention Name(s)
Brodalumab
Other Intervention Name(s)
AMG 827
Intervention Description
3 single subcutaneous (SC) injections at day 1 and weeks 1, 2, 4, 6, 8, and 10
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
3 single SC injections at day 1 and weeks 1, 2, 4, 6, 8, and 10
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Intervention Description
Two methotrexate dose adjustments were allowed in the event of methotrexate toxicity, however, doses < 7.5 mg/week necessitated discontinuation from study.
Intervention Type
Dietary Supplement
Intervention Name(s)
folic acid
Intervention Description
at least 5 mg per week
Primary Outcome Measure Information:
Title
Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12
Description
A positive ACR50 response is defined if the following 3 criteria for improvement from baseline were met:
50% improvement in 68 tender joint count;
50% improvement in 66 swollen joint count; and
50% improvement in at least 3 of the 5 following parameters:
Patient's assessment of joint pain (measured on a 100 mm visual analog scale [VAS]),
Patient's global assessment of disease activity (measured on a 0-10 Likert scale),
Physician's global assessment of disease activity (measured on a 0-10 Likert scale),
Patient's self assessment of disability (Health Assessment Questionnaire - Disability Index [HAQ-DI]),
Acute phase reactant: erythrocyte sedimentation rate (ESR) or C-Reactive Protein (CRP), whichever has bigger improvement.
Time Frame
Baseline, week 12
Secondary Outcome Measure Information:
Title
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12
Description
A positive ACR20 response is defined if the following 3 criteria for improvement from baseline were met:
20% improvement in 68 tender joint count;
20% improvement in 66 swollen joint count; and
20% improvement in at least 3 of the 5 following parameters:
Patient's assessment of joint pain (measured on a 100 mm visual analog scale [VAS]),
Patient's global assessment of disease activity (measured on a 0-10 Likert scale),
Physician's global assessment of disease activity (measured on a 0-10 Likert scale),
Patient's self assessment of disability (Health Assessment Questionnaire - Disability Index [HAQ-DI]),
Acute phase reactant: erythrocyte sedimentation rate (ESR) or C-Reactive Protein (CRP), whichever has bigger improvement.
Time Frame
Baseline, Week 12
Title
Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12
Description
A positive ACR70 response is defined if the following 3 criteria for improvement from baseline were met:
70% improvement in 68 tender joint count;
70% improvement in 66 swollen joint count; and
70% improvement in at least 3 of the 5 following parameters:
Patient's assessment of joint pain (measured on a 100 mm visual analog scale [VAS]),
Patient's global assessment of disease activity (measured on a 0-10 Likert scale),
Physician's global assessment of disease activity (measured on a 0-10 Likert scale),
Patient's self assessment of disability (Health Assessment Questionnaire - Disability Index [HAQ-DI]),
Acute phase reactant: erythrocyte sedimentation rate (ESR) or C-Reactive Protein (CRP), whichever has bigger improvement.
Time Frame
Baseline, week 12
Title
Disease Activity Score 28 (DAS28) at Week 12
Description
The DAS28 is a composite score to measure disease activity in patients with rheumatoid arthritis, derived from the following variables: • The number of tender joints assessed using the 28-jount count and number of swollen joints assessed using the 28-joint count; • Erythrocyte sedimentation rate (ESR); • Patient's global assessment of disease activity (measured on a 0-10 Likert scale). The DAS28 score ranges from 0 to 10, with higher scores indicating more severe disease activity.
Time Frame
Week 12
Title
Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation
Description
AEs are defined as any untoward medical occurrence, that does not necessarily have a causal relationship with this treatment. SAEs are defined as an AE that: is fatal; is life threatening (places the subject at immediate risk of death); requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; other significant medical hazard. The severity of events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v 4.0: mild=grade 1, moderate=grade 2, severe=grade 3, life-threatening=grade 4, death=grade 5.
Time Frame
From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
Title
Pharmacokinetics (PK) of Brodalumab: Maximum Observed Concentration (Cmax)
Time Frame
Week 8: Day 59-Day 61 (44-100 hours post-dose), Day 64 (160-176 hours post-dose), Week 10: pre-dose
Title
PK of Brodalumab: Time to Maximum Observed Concentration (Tmax)
Time Frame
Week 8: Day 59-Day 61 (44-100 hours post-dose), Day 64 (160-176 hours post-dose), Week 10: pre-dose
Title
PK of Brodalumab: Area Under the Curve During the Dosing Interval (AUCtau)
Time Frame
Week 8: Day 59-Day 61 (44-100 hours post-dose), Day 64 (160-176 hours post-dose), Week 10: pre-dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Active RA for least 6 months
Current RA defined as ≥ 6 swollen joints (out of 66 joints examined) and ≥ 8 tender/painful joints (out of 68 joints examined) at screening and baseline (swollen and tender/painful joint count must not include distal interphalangeal joints) and at least 1 of the following at screening: Erythrocyte sedimentation rate ≥ 28 mm or C-reactive protein > 15 mg/L
At least 1 of the following at screening: Rheumatoid factor positive or Anti-cyclic citrullinated peptide antibody positive
Currently taking methotrexate for ≥ 12 weeks and on a stable dose of methotrexate at 15 to 25 mg weekly for ≥ 4 weeks at day -1.
Exclusion Criteria:
Prosthetic joint infection within 5 years of screening or native joint infection within 1 year of screening
Class IV RA
Felty's syndrome
Presence of serious infection
Significant concurrent medical conditions
Pregnant or breast feeding
Significant Laboratory abnormalities
Any disease-modifying anti-rheumatic drug (DMARD) other than methotrexate within 28 days
Leflunomide or live vaccines within 3 months
Previous use of any experimental or commercially available biologic DMARD
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
25877498
Citation
Pavelka K, Chon Y, Newmark R, Lin SL, Baumgartner S, Erondu N. A study to evaluate the safety, tolerability, and efficacy of brodalumab in subjects with rheumatoid arthritis and an inadequate response to methotrexate. J Rheumatol. 2015 Jun;42(6):912-9. doi: 10.3899/jrheum.141271. Epub 2015 Apr 15.
Results Reference
background
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website
Learn more about this trial
Brodalumab (AMG 827) in Rheumatoid Arthritis (RA) Participants With Inadequate Response to Methotrexate
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