Trial Outcomes & Findings for Brodalumab (AMG 827) in Rheumatoid Arthritis (RA) Participants With Inadequate Response to Methotrexate (NCT NCT00950989)
NCT ID: NCT00950989
Last Updated: 2021-12-21
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
252 participants
Primary outcome timeframe
Baseline, week 12
Results posted on
2021-12-21
Participant Flow
This study was conducted in the following countries: Bulgaria, Canada, Czech Republic, Hungary, Latvia, Mexico, Poland, United Kingdom, United States.
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.
Participant milestones
| Measure |
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 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).
|
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).
|
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).
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
63
|
63
|
63
|
63
|
|
Overall Study
COMPLETED
|
59
|
60
|
60
|
63
|
|
Overall Study
NOT COMPLETED
|
4
|
3
|
3
|
0
|
Reasons for withdrawal
| Measure |
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 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).
|
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).
|
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).
|
|---|---|---|---|---|
|
Overall Study
Death
|
0
|
0
|
1
|
0
|
|
Overall Study
Administrative Decision
|
0
|
1
|
0
|
0
|
|
Overall Study
Disease Progression
|
0
|
0
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
2
|
1
|
0
|
0
|
|
Overall Study
Adverse Event
|
2
|
1
|
1
|
0
|
Baseline Characteristics
Brodalumab (AMG 827) in Rheumatoid Arthritis (RA) Participants With Inadequate Response to Methotrexate
Baseline characteristics by cohort
| Measure |
Placebo
n=63 Participants
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
n=63 Participants
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
n=63 Participants
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).
|
Brodalumab 210 mg
n=63 Participants
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).
|
Total
n=252 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Customized
< 65 years
|
57 Participants
n=5 Participants
|
60 Participants
n=7 Participants
|
53 Participants
n=5 Participants
|
58 Participants
n=4 Participants
|
228 Participants
n=21 Participants
|
|
Age, Customized
>= 65 years
|
6 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
24 Participants
n=21 Participants
|
|
Sex: Female, Male
Female
|
51 Participants
n=5 Participants
|
50 Participants
n=7 Participants
|
49 Participants
n=5 Participants
|
50 Participants
n=4 Participants
|
200 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
13 Participants
n=4 Participants
|
52 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
White or Caucasian
|
48 Participants
n=5 Participants
|
53 Participants
n=7 Participants
|
50 Participants
n=5 Participants
|
56 Participants
n=4 Participants
|
207 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
14 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
40 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Baseline, week 12Population: Full Analysis Set: all randomized participants with an assessment. Non-responder imputation.
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.
Outcome measures
| Measure |
Placebo
n=63 Participants
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
n=63 Participants
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
n=63 Participants
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).
|
Brodalumab 210 mg
n=63 Participants
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).
|
|---|---|---|---|---|
|
Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12
|
12.7 percentage of participants
|
15.9 percentage of participants
|
15.9 percentage of participants
|
9.5 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: Full Analysis Set: all randomized participants with an assessment. Non-responder imputation.
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.
Outcome measures
| Measure |
Placebo
n=63 Participants
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
n=63 Participants
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
n=63 Participants
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).
|
Brodalumab 210 mg
n=63 Participants
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).
|
|---|---|---|---|---|
|
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12
|
42.9 percentage of partcipants
|
39.7 percentage of partcipants
|
36.5 percentage of partcipants
|
46.0 percentage of partcipants
|
SECONDARY outcome
Timeframe: Baseline, week 12Population: Full Analysis Set: all randomized participants with an assessment. Non-responder imputation.
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.
Outcome measures
| Measure |
Placebo
n=63 Participants
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
n=63 Participants
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
n=63 Participants
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).
|
Brodalumab 210 mg
n=63 Participants
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).
|
|---|---|---|---|---|
|
Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12
|
3.2 percentage of participants
|
3.2 percentage of participants
|
3.2 percentage of participants
|
0.0 percentage of participants
|
SECONDARY outcome
Timeframe: Week 12Population: Full Analysis Set: all randomized participants with an assessment. Last observation carried forward (LOCF).
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.
Outcome measures
| Measure |
Placebo
n=63 Participants
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
n=61 Participants
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
n=63 Participants
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).
|
Brodalumab 210 mg
n=63 Participants
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).
|
|---|---|---|---|---|
|
Disease Activity Score 28 (DAS28) at Week 12
|
5.0 score on a scale
Standard Error 0.2
|
4.9 score on a scale
Standard Error 0.2
|
5.1 score on a scale
Standard Error 0.2
|
5.1 score on a scale
Standard Error 0.2
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Placebo
n=63 Participants
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
n=63 Participants
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
n=63 Participants
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).
|
Brodalumab 210 mg
n=63 Participants
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).
|
|---|---|---|---|---|
|
Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation
AEs
|
32 Participants
|
32 Participants
|
40 Participants
|
32 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation
SAEs
|
2 Participants
|
1 Participants
|
1 Participants
|
3 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation
Fatal AEs
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
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
|
1 Participants
|
2 Participants
|
0 Participants
|
|
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
|
1 Participants
|
1 Participants
|
2 Participants
|
|
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
|
3 Participants
|
2 Participants
|
4 Participants
|
|
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
|
8 Participants
|
14 Participants
|
11 Participants
|
|
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
|
0 Participants
|
0 Participants
|
0 Participants
|
|
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
|
0 Participants
|
0 Participants
|
0 Participants
|
|
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
|
1 Participants
|
0 Participants
|
0 Participants
|
|
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
|
1 Participants
|
0 Participants
|
2 Participants
|
|
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
|
1 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Week 8: Day 59-Day 61 (44-100 hours post-dose), Day 64 (160-176 hours post-dose), Week 10: pre-dosePopulation: Participants who received brodalumab with an evaluable PK measurement.
Outcome measures
| Measure |
Placebo
n=15 Participants
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
n=13 Participants
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
n=12 Participants
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).
|
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).
|
|---|---|---|---|---|
|
Pharmacokinetics (PK) of Brodalumab: Maximum Observed Concentration (Cmax)
|
3.02 µg/mL
Standard Deviation 1.61
|
7.85 µg/mL
Standard Deviation 4.37
|
17.9 µg/mL
Standard Deviation 12.8
|
—
|
SECONDARY outcome
Timeframe: Week 8: Day 59-Day 61 (44-100 hours post-dose), Day 64 (160-176 hours post-dose), Week 10: pre-dosePopulation: Participants who received brodalumab with an evaluable PK measurement.
Outcome measures
| Measure |
Placebo
n=15 Participants
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
n=13 Participants
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
n=12 Participants
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).
|
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).
|
|---|---|---|---|---|
|
PK of Brodalumab: Time to Maximum Observed Concentration (Tmax)
|
1.94 days
Interval 1.84 to 3.73
|
2.00 days
Interval 1.84 to 6.92
|
1.96 days
Interval 1.91 to 6.99
|
—
|
SECONDARY outcome
Timeframe: Week 8: Day 59-Day 61 (44-100 hours post-dose), Day 64 (160-176 hours post-dose), Week 10: pre-dosePopulation: Participants who received AMG 827 with an evaluable PK measurement.
Outcome measures
| Measure |
Placebo
n=15 Participants
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
n=13 Participants
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
n=12 Participants
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).
|
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).
|
|---|---|---|---|---|
|
PK of Brodalumab: Area Under the Curve During the Dosing Interval (AUCtau)
|
18.1 µg*day/mL
Standard Deviation 15.2
|
73.3 µg*day/mL
Standard Deviation 52.7
|
199 µg*day/mL
Standard Deviation 161
|
—
|
Adverse Events
Placebo
Serious events: 2 serious events
Other events: 18 other events
Deaths: 0 deaths
Brodalumab 70 mg
Serious events: 1 serious events
Other events: 19 other events
Deaths: 0 deaths
Brodalumab 140 mg
Serious events: 1 serious events
Other events: 25 other events
Deaths: 0 deaths
Brodalumab 210 mg
Serious events: 3 serious events
Other events: 12 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=63 participants at risk
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
n=63 participants at risk
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
n=63 participants at risk
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
n=63 participants at risk
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).
|
|---|---|---|---|---|
|
Cardiac disorders
Cardiopulmonary failure
|
0.00%
0/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
0.00%
0/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
1.6%
1/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
0.00%
0/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
|
Eye disorders
Blepharitis
|
0.00%
0/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
1.6%
1/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
0.00%
0/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
0.00%
0/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
|
Injury, poisoning and procedural complications
Lumbar vertebral fracture
|
0.00%
0/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
0.00%
0/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
0.00%
0/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
1.6%
1/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
|
Injury, poisoning and procedural complications
Tibia fracture
|
1.6%
1/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
0.00%
0/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
0.00%
0/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
0.00%
0/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
|
Musculoskeletal and connective tissue disorders
Osteoporotic fracture
|
0.00%
0/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
0.00%
0/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
0.00%
0/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
1.6%
1/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
|
1.6%
1/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
0.00%
0/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
0.00%
0/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
0.00%
0/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
|
Psychiatric disorders
Suicide attempt
|
0.00%
0/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
0.00%
0/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
0.00%
0/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
1.6%
1/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
|
Vascular disorders
Thrombosis
|
0.00%
0/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
0.00%
0/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
0.00%
0/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
1.6%
1/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
Other adverse events
| Measure |
Placebo
n=63 participants at risk
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
n=63 participants at risk
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
n=63 participants at risk
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
n=63 participants at risk
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).
|
|---|---|---|---|---|
|
General disorders
Injection site pain
|
6.3%
4/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
3.2%
2/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
3.2%
2/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
3.2%
2/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
|
Infections and infestations
Nasopharyngitis
|
3.2%
2/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
4.8%
3/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
6.3%
4/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
6.3%
4/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
|
Infections and infestations
Upper respiratory tract infection
|
1.6%
1/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
6.3%
4/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
7.9%
5/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
4.8%
3/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
|
Infections and infestations
Urinary tract infection
|
1.6%
1/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
3.2%
2/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
7.9%
5/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
6.3%
4/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
|
7.9%
5/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
6.3%
4/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
11.1%
7/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
0.00%
0/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
|
Nervous system disorders
Headache
|
6.3%
4/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
4.8%
3/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
4.8%
3/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
1.6%
1/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.3%
4/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
3.2%
2/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
3.2%
2/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
1.6%
1/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
|
Vascular disorders
Hypertension
|
6.3%
4/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
3.2%
2/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
4.8%
3/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
3.2%
2/63 • From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
- Publication restrictions are in place
Restriction type: OTHER