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Study in participants with RA who have an inadequate response to methotrexate.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | 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 | Experimental | 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 | Experimental | 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 | Placebo Comparator | 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). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Brodalumab | Drug | 3 single subcutaneous (SC) injections at day 1 and weeks 1, 2, 4, 6, 8, and 10 |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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:
| Baseline, week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| 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:
|
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| MD | Amgen | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25877498 | Background | 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. |
| Label | URL |
|---|---|
| AmgenTrials clinical trials website | View source |
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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.
This study was conducted in the following countries: Bulgaria, Canada, Czech Republic, Hungary, Latvia, Mexico, Poland, United Kingdom, United States.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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). |
| FG001 | 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). |
| FG002 | 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). |
| FG003 | 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). |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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). |
| BG001 | Brodalumab 70 mg |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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:
| Full Analysis Set: all randomized participants with an assessment. Non-responder imputation. | Posted | Number | percentage of participants | Baseline, week 12 |
|
From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiopulmonary failure | Cardiac disorders | MedDRA 13.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Injection site pain | General disorders | MedDRA 13.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Amgen Inc. | 866-572-6436 | medinfo@amgen.com |
| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| D001327 | Autoimmune Diseases |
| D009140 | Musculoskeletal Diseases |
| D007592 | Joint Diseases |
| D001168 | Arthritis |
| D003240 | Connective Tissue Diseases |
| D012216 | Rheumatic Diseases |
| ID | Term |
|---|---|
| D017437 | Skin and Connective Tissue Diseases |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C571216 | brodalumab |
| D008727 | Methotrexate |
| D005492 | Folic Acid |
| ID | Term |
|---|---|
| D000630 | Aminopterin |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
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|
| Placebo | Drug | 3 single SC injections at day 1 and weeks 1, 2, 4, 6, 8, and 10 |
|
| Methotrexate | Drug | Two methotrexate dose adjustments were allowed in the event of methotrexate toxicity, however, doses < 7.5 mg/week necessitated discontinuation from study. |
|
| folic acid | Dietary Supplement | at least 5 mg per week |
|
| Baseline, Week 12 |
| 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:
| Baseline, week 12 |
| 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. | Week 12 |
| 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. | From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132). |
| 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: 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 |
| 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 |
| Administrative Decision |
|
| Disease Progression |
|
| Withdrawal by Subject |
|
| Adverse Event |
|
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).
| BG002 | 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). |
| BG003 | 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). |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| 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). |
| OG001 | 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). |
| OG002 | 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). |
| OG003 | 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). |
|
|
|
| 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:
| Full Analysis Set: all randomized participants with an assessment. Non-responder imputation. | Posted | Number | percentage of partcipants | Baseline, Week 12 |
|
|
|
|
| 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:
| Full Analysis Set: all randomized participants with an assessment. Non-responder imputation. | Posted | Number | percentage of participants | Baseline, week 12 |
|
|
|
|
| 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. | Full Analysis Set: all randomized participants with an assessment. Last observation carried forward (LOCF). | Posted | Least Squares Mean | Standard Error | score on a scale | Week 12 |
|
|
|
|
| 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. | Safety Analysis Set: all randomized participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132). |
|
|
|
| Secondary | Pharmacokinetics (PK) of Brodalumab: Maximum Observed Concentration (Cmax) | Participants who received brodalumab with an evaluable PK measurement. | Posted | Mean | Standard Deviation | µg/mL | Week 8: Day 59-Day 61 (44-100 hours post-dose), Day 64 (160-176 hours post-dose), Week 10: pre-dose |
|
|
|
| Secondary | PK of Brodalumab: Time to Maximum Observed Concentration (Tmax) | Participants who received brodalumab with an evaluable PK measurement. | Posted | Median | Full Range | days | Week 8: Day 59-Day 61 (44-100 hours post-dose), Day 64 (160-176 hours post-dose), Week 10: pre-dose |
|
|
|
| Secondary | PK of Brodalumab: Area Under the Curve During the Dosing Interval (AUCtau) | Participants who received AMG 827 with an evaluable PK measurement. | Posted | Mean | Standard Deviation | µg*day/mL | Week 8: Day 59-Day 61 (44-100 hours post-dose), Day 64 (160-176 hours post-dose), Week 10: pre-dose |
|
|
|
| 2 |
| 63 |
| 18 |
| 63 |
| EG001 | 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). | 1 | 63 | 19 | 63 |
| EG002 | 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 methotrexateand folic acid supplementation (at least 5 mg per week). | 1 | 63 | 25 | 63 |
| EG003 | 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). | 3 | 63 | 12 | 63 |
| Blepharitis | Eye disorders | MedDRA 13.1 | Systematic Assessment |
|
| Lumbar vertebral fracture | Injury, poisoning and procedural complications | MedDRA 13.1 | Systematic Assessment |
|
| Tibia fracture | Injury, poisoning and procedural complications | MedDRA 13.1 | Systematic Assessment |
|
| Osteoporotic fracture | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| Rheumatoid arthritis | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| Suicide attempt | Psychiatric disorders | MedDRA 13.1 | Systematic Assessment |
|
| Thrombosis | Vascular disorders | MedDRA 13.1 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
|
| Rheumatoid arthritis | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 13.1 | Systematic Assessment |
|
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.
| D000072471 |
| Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| 0.993 |
Adjusted p-value is based on a combination of sequential testing and the Hommel procedure to control the overall significance level for all the comparisons. |
| Superiority |
| Cochran-Mantel-Haenszel | 0.412 | P-value is nominal p-value without multiplicity adjustment based on Cochran-Mantel-Haenszel test adjusting for sex. | Difference in response rates | -6.3 | 2-Sided | 95 | -23.4 | 10.7 | Superiority |
| Sequential testing + Hommel procedures | 0.740 | Adjusted p-value is based on a combination of sequential testing and the Hommel procedure to control the overall significance level for all the comparisons. | Superiority |
| Cochran-Mantel-Haenszel | 0.740 | P-value is nominal p-value without multiplicity adjustment based on Cochran-Mantel-Haenszel test adjusting for sex. | Difference in response rates | 3.2 | 2-Sided | 95 | -14.2 | 20.5 | Superiority |
| Sequential testing + Hommel procedure | 0.993 | Adjusted p-value is based on a combination of sequential testing and the Hommel procedure to control the overall significance level for all the comparisons. | Superiority |
| 0.993 |
Adjusted p-value is based on a combination of sequential testing and the Hommel procedure to control the overall significance level for all the comparisons. |
| Superiority |
| Cochran-Mantel-Haenszel | 0.993 | P-value is nominal p-value without multiplicity adjustment based on Cochran-Mantel-Haenszel test adjusting for sex. | Difference in response rates | 0.0 | 2-Sided | 95 | -6.1 | 6.1 | Superiority |
| Sequential testing + Hommel procedure | 0.993 | Adjusted p-value is based on a combination of sequential testing and the Hommel procedure to control the overall significance level for all the comparisons. | Superiority |
| Cochran-Mantel-Haenszel | 0.159 | P-value is nominal p-value without multiplicity adjustment based on Cochran-Mantel-Haenszel test adjusting for sex. | Difference in response rates | -3.2 | 2-Sided | 95 | -7.5 | 1.2 | Superiority |
| Sequential testing + Hommel procedure | 0.797 | Adjusted p-value is based on a combination of sequential testing and the Hommel procedure to control the overall significance level for all the comparisons. | Superiority |
| ANCOVA |
| 0.906 |
P-value is nominal without multiplicity adjustment based on ANCOVA model adjusting for sex and baseline DAS28 score. |
| LS mean of difference |
| 0.0 |
| Standard Error of the Mean |
| 0.2 |
| 2-Sided |
| 95 |
| -0.5 |
| 0.5 |
| Superiority |
| ANCOVA | 0.849 | P-value is nominal without multiplicity adjustment based on ANCOVA model adjusting for sex and baseline DAS28 score. | LS mean of difference | 0.0 | Standard Error of the Mean | 0.2 | 2-Sided | 95 | -0.5 | 0.5 | Superiority |
| SAEs |
|
| Fatal AEs |
|
| AEs leading to Study Discontinuation |
|
| AEs leading to Study Drug Discontinuation |
|
| CTCAE Grades 3, 4, 5 AEs |
|
| AEs Related to Study Drug |
|
| SAEs Related to Study Drug |
|
| Fatal AEs Related to Study Drug |
|
| AEs Related to Study Drug Leading to Study Discontinuation |
|
| AEs Related to Study Drug Leading to Study Drug Discontinuation |
|
| CTCAE Grades 3, 4, 5 AEs Related to Study Drug |
|