Brodalumab (AMG 827) in Rheumatoid Arthritis (RA) Participants With Inadequate Response to Methotrexate
- Conditions
- Rheumatoid Arthritis
- Interventions
- Registration Number
- NCT00950989
- Lead Sponsor
- Amgen
- Brief Summary
Study in participants with RA who have an inadequate response to methotrexate.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 252
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo folic acid 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). Brodalumab 70 mg folic acid 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). Placebo Placebo 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). Brodalumab 140 mg folic acid 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). Brodalumab 210 mg Brodalumab 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). Brodalumab 210 mg Methotrexate 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). Brodalumab 210 mg folic acid 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). Placebo Methotrexate 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). Brodalumab 70 mg Brodalumab 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). Brodalumab 70 mg Methotrexate 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). Brodalumab 140 mg Methotrexate 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). Brodalumab 140 mg Brodalumab 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).
- Primary Outcome Measures
Name Time Method Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12 Baseline, 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
Name Time Method Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12 Baseline, 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.Disease Activity Score 28 (DAS28) at Week 12 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 From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132). 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.
PK of Brodalumab: Time to Maximum Observed Concentration (Tmax) Week 8: Day 59-Day 61 (44-100 hours post-dose), Day 64 (160-176 hours post-dose), Week 10: pre-dose Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12 Baseline, 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.Pharmacokinetics (PK) of Brodalumab: Maximum Observed Concentration (Cmax) Week 8: Day 59-Day 61 (44-100 hours post-dose), Day 64 (160-176 hours post-dose), Week 10: pre-dose PK of Brodalumab: Area Under the Curve During the Dosing Interval (AUCtau) Week 8: Day 59-Day 61 (44-100 hours post-dose), Day 64 (160-176 hours post-dose), Week 10: pre-dose