Rheumatoid Arthritis
Conditions
Keywords
Autoimmune Diseases, Musculoskeletal Diseases, Joint Diseases, Arthritis, Connective Tissue Diseases, Arthritis, Rheumatoid, Rheumatic Diseases
Brief summary
Study in participants with RA who have an inadequate response to methotrexate.
Interventions
DRUGBrodalumab
3 single subcutaneous (SC) injections at day 1 and weeks 1, 2, 4, 6, 8, and 10
DRUGPlacebo
3 single SC injections at day 1 and weeks 1, 2, 4, 6, 8, and 10
DRUGMethotrexate
Two methotrexate dose adjustments were allowed in the event of methotrexate toxicity, however, doses \< 7.5 mg/week necessitated discontinuation from study.
DIETARY_SUPPLEMENTfolic acid
at least 5 mg per week
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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 | — |
| 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 | — |
| 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. |
Participant flow
Recruitment details
This study was conducted in the following countries: Bulgaria, Canada, Czech Republic, Hungary, Latvia, Mexico, Poland, United Kingdom, United States.
Pre-assignment details
Participants were randomized in a 1:1:1:1 ratio to receive brodalumab (doses of 70, 140, or 210 mg) or placebo. Randomization was stratified by sex with enrollment of women limited to 200 participants.
Participants by arm
| Arm | Count |
|---|---|
| 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). | 63 |
| Brodalumab 70 mg 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). | 63 |
| Brodalumab 140 mg 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 methotrexate and folic acid supplementation (at least 5 mg per week). | 63 |
| Brodalumab 210 mg 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). | 63 |
| Total | 252 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Administrative Decision | 0 | 1 | 0 | 0 |
| Overall Study | Adverse Event | 2 | 1 | 1 | 0 |
| Overall Study | Death | 0 | 0 | 1 | 0 |
| Overall Study | Disease Progression | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | Brodalumab 70 mg | Brodalumab 140 mg | Brodalumab 210 mg | Total |
|---|---|---|---|---|---|
| Age, Customized < 65 years | 57 Participants | 60 Participants | 53 Participants | 58 Participants | 228 Participants |
| Age, Customized >= 65 years | 6 Participants | 3 Participants | 10 Participants | 5 Participants | 24 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 14 Participants | 8 Participants | 12 Participants | 6 Participants | 40 Participants |
| Race/Ethnicity, Customized White or Caucasian | 48 Participants | 53 Participants | 50 Participants | 56 Participants | 207 Participants |
| Sex: Female, Male Female | 51 Participants | 50 Participants | 49 Participants | 50 Participants | 200 Participants |
| Sex: Female, Male Male | 12 Participants | 13 Participants | 14 Participants | 13 Participants | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 18 / 63 | 19 / 63 | 25 / 63 | 12 / 63 |
| serious Total, serious adverse events | 2 / 63 | 1 / 63 | 1 / 63 | 3 / 63 |
Outcome results
Primary
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.
Time frame: Baseline, week 12
Population: Full Analysis Set: all randomized participants with an assessment. Non-responder imputation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12 | 12.7 percentage of participants |
| Brodalumab 70 mg | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12 | 15.9 percentage of participants |
| Brodalumab 140 mg | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12 | 15.9 percentage of participants |
| Brodalumab 210 mg | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12 | 9.5 percentage of participants |
p-value: 0.59895% CI: [-9, 15.4]Cochran-Mantel-Haenszel
p-value: 0.993Sequential testing + Hommel procedure
p-value: 0.63595% CI: [-9, 15.4]Cochran-Mantel-Haenszel
p-value: 0.74Sequential testing + Hommel procedure
p-value: 0.57295% CI: [-14.1, 7.8]Cochran-Mantel-Haenszel
p-value: 0.572Sequential testing + Hommel procedure
Secondary
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.
Time frame: Week 12
Population: Full Analysis Set: all randomized participants with an assessment. Last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Disease Activity Score 28 (DAS28) at Week 12 | 5.0 score on a scale | Standard Error 0.2 |
| Brodalumab 70 mg | Disease Activity Score 28 (DAS28) at Week 12 | 4.9 score on a scale | Standard Error 0.2 |
| Brodalumab 140 mg | Disease Activity Score 28 (DAS28) at Week 12 | 5.1 score on a scale | Standard Error 0.2 |
| Brodalumab 210 mg | Disease Activity Score 28 (DAS28) at Week 12 | 5.1 score on a scale | Standard Error 0.2 |
p-value: 0.45995% CI: [-0.7, 0.3]ANCOVA
p-value: 0.90695% CI: [-0.5, 0.5]ANCOVA
p-value: 0.84995% CI: [-0.5, 0.5]ANCOVA
Secondary
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.
Time frame: From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
Population: Safety Analysis Set: all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs Related to Study Drug | 12 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs leading to Study Discontinuation | 2 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | CTCAE Grades 3, 4, 5 AEs Related to Study Drug | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | Fatal AEs Related to Study Drug | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs Related to Study Drug Leading to Study Drug Discontinuation | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs leading to Study Drug Discontinuation | 1 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | Fatal AEs | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | SAEs | 2 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | SAEs Related to Study Drug | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | CTCAE Grades 3, 4, 5 AEs | 4 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs | 32 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs Related to Study Drug Leading to Study Discontinuation | 1 Participants |
| Brodalumab 70 mg | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | SAEs | 1 Participants |
| Brodalumab 70 mg | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs Related to Study Drug | 8 Participants |
| Brodalumab 70 mg | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs | 32 Participants |
| Brodalumab 70 mg | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | Fatal AEs Related to Study Drug | 0 Participants |
| Brodalumab 70 mg | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | SAEs Related to Study Drug | 0 Participants |
| Brodalumab 70 mg | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | Fatal AEs | 0 Participants |
| Brodalumab 70 mg | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs Related to Study Drug Leading to Study Drug Discontinuation | 1 Participants |
| Brodalumab 70 mg | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs leading to Study Discontinuation | 1 Participants |
| Brodalumab 70 mg | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | CTCAE Grades 3, 4, 5 AEs Related to Study Drug | 1 Participants |
| Brodalumab 70 mg | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs leading to Study Drug Discontinuation | 1 Participants |
| Brodalumab 70 mg | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs Related to Study Drug Leading to Study Discontinuation | 1 Participants |
| Brodalumab 70 mg | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | CTCAE Grades 3, 4, 5 AEs | 3 Participants |
| Brodalumab 140 mg | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | Fatal AEs Related to Study Drug | 0 Participants |
| Brodalumab 140 mg | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs | 40 Participants |
| Brodalumab 140 mg | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | SAEs | 1 Participants |
| Brodalumab 140 mg | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | Fatal AEs | 1 Participants |
| Brodalumab 140 mg | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs leading to Study Discontinuation | 2 Participants |
| Brodalumab 140 mg | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs leading to Study Drug Discontinuation | 1 Participants |
| Brodalumab 140 mg | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | CTCAE Grades 3, 4, 5 AEs | 2 Participants |
| Brodalumab 140 mg | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs Related to Study Drug | 14 Participants |
| Brodalumab 140 mg | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | SAEs Related to Study Drug | 0 Participants |
| Brodalumab 140 mg | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | CTCAE Grades 3, 4, 5 AEs Related to Study Drug | 0 Participants |
| Brodalumab 140 mg | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs Related to Study Drug Leading to Study Discontinuation | 0 Participants |
| Brodalumab 140 mg | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs Related to Study Drug Leading to Study Drug Discontinuation | 0 Participants |
| Brodalumab 210 mg | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | Fatal AEs Related to Study Drug | 0 Participants |
| Brodalumab 210 mg | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | CTCAE Grades 3, 4, 5 AEs | 4 Participants |
| Brodalumab 210 mg | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs leading to Study Drug Discontinuation | 2 Participants |
| Brodalumab 210 mg | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs | 32 Participants |
| Brodalumab 210 mg | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs Related to Study Drug Leading to Study Discontinuation | 0 Participants |
| Brodalumab 210 mg | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs leading to Study Discontinuation | 0 Participants |
| Brodalumab 210 mg | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | Fatal AEs | 0 Participants |
| Brodalumab 210 mg | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | CTCAE Grades 3, 4, 5 AEs Related to Study Drug | 0 Participants |
| Brodalumab 210 mg | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs Related to Study Drug Leading to Study Drug Discontinuation | 2 Participants |
| Brodalumab 210 mg | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | SAEs Related to Study Drug | 0 Participants |
| Brodalumab 210 mg | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs Related to Study Drug | 11 Participants |
| Brodalumab 210 mg | Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | SAEs | 3 Participants |
Secondary
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.
Time frame: Baseline, Week 12
Population: Full Analysis Set: all randomized participants with an assessment. Non-responder imputation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12 | 42.9 percentage of partcipants |
| Brodalumab 70 mg | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12 | 39.7 percentage of partcipants |
| Brodalumab 140 mg | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12 | 36.5 percentage of partcipants |
| Brodalumab 210 mg | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12 | 46.0 percentage of partcipants |
p-value: 0.72895% CI: [-20.4, 14]Cochran-Mantel-Haenszel
p-value: 0.993Sequential testing + Hommel procedure
p-value: 0.41295% CI: [-23.4, 10.7]Cochran-Mantel-Haenszel
p-value: 0.74Sequential testing + Hommel procedures
p-value: 0.7495% CI: [-14.2, 20.5]Cochran-Mantel-Haenszel
p-value: 0.993Sequential testing + Hommel procedure
Secondary
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.
Time frame: Baseline, week 12
Population: Full Analysis Set: all randomized participants with an assessment. Non-responder imputation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12 | 3.2 percentage of participants |
| Brodalumab 70 mg | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12 | 3.2 percentage of participants |
| Brodalumab 140 mg | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12 | 3.2 percentage of participants |
| Brodalumab 210 mg | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12 | 0.0 percentage of participants |
p-value: 0.98495% CI: [-6.1, 6.1]Cochran-Mantel-Haenszel
p-value: 0.993Sequential testing + Hommel procedure
p-value: 0.99395% CI: [-6.1, 6.1]Cochran-Mantel-Haenszel
p-value: 0.993Sequential testing + Hommel procedure
p-value: 0.15995% CI: [-7.5, 1.2]Cochran-Mantel-Haenszel
p-value: 0.797Sequential testing + Hommel procedure
Secondary
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
Population: Participants who received brodalumab with an evaluable PK measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacokinetics (PK) of Brodalumab: Maximum Observed Concentration (Cmax) | 3.02 µg/mL | Standard Deviation 1.61 |
| Brodalumab 70 mg | Pharmacokinetics (PK) of Brodalumab: Maximum Observed Concentration (Cmax) | 7.85 µg/mL | Standard Deviation 4.37 |
| Brodalumab 140 mg | Pharmacokinetics (PK) of Brodalumab: Maximum Observed Concentration (Cmax) | 17.9 µg/mL | Standard Deviation 12.8 |
Secondary
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
Population: Participants who received AMG 827 with an evaluable PK measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | PK of Brodalumab: Area Under the Curve During the Dosing Interval (AUCtau) | 18.1 µg*day/mL | Standard Deviation 15.2 |
| Brodalumab 70 mg | PK of Brodalumab: Area Under the Curve During the Dosing Interval (AUCtau) | 73.3 µg*day/mL | Standard Deviation 52.7 |
| Brodalumab 140 mg | PK of Brodalumab: Area Under the Curve During the Dosing Interval (AUCtau) | 199 µg*day/mL | Standard Deviation 161 |
Secondary
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
Population: Participants who received brodalumab with an evaluable PK measurement.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | PK of Brodalumab: Time to Maximum Observed Concentration (Tmax) | 1.94 days |
| Brodalumab 70 mg | PK of Brodalumab: Time to Maximum Observed Concentration (Tmax) | 2.00 days |
| Brodalumab 140 mg | PK of Brodalumab: Time to Maximum Observed Concentration (Tmax) | 1.96 days |