Arthritis, Rheumatoid
Conditions
Keywords
arthritis, rheumatoid
Brief summary
The purpose of this open-label study is to evaluate the long-term safety and efficacy of ABP 501 in adults with moderate to severe rheumatoid arthritis (RA).
Interventions
BIOLOGICALABP 501
Solution for subcutaneous injection in a syringe containing 40 mg/0.8 mL ABP 501
Sponsors
Amgen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 81 Years
Healthy volunteers
No
Inclusion criteria
* Subject was randomized into protocol 20120262 (NCT01970475) and completed the week 26 visit
Exclusion criteria
* Subject experienced a serious adverse event (SAE) or an adverse event (AE) in the 20120262 study that could cause extension treatment to be detrimental * Subject completed study 20120262 but cannot be dosed within 4 weeks of the week 26 visit of study 20120262 * Current infection requiring the use of oral or intravenous antibiotics Other Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | From the first dose of study drug in the extension study to 28 days following the last dose; 72 weeks | Adverse events (AEs) were graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 according to the following scale: 1 = mild; 2 = moderate; 3 = severe; 4 = life-threatening; 5 = fatal. A treatment-related AE is defined as an event where the answer to the question is there a reasonable possibility that the event may have been caused by the Investigational Medicinal Product was yes. A serious adverse event is defined as an AE that meets at least 1 of the following serious criteria: * fatal * life threatening (places the subject at immediate risk of death) * requires inpatient hospitalization or prolongation of existing hospitalization * results in persistent or significant disability/incapacity * congenital anomaly/birth defect * other medically important serious event. |
| Number of Participants With Grade ≥ 3 Hematology and Chemistry Laboratory Results | From the first dose of study drug in the extension study to 28 days following the last dose; 72 weeks | Laboratory results were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 according to the following scale: 1 = mild; 2 = moderate; 3 = severe; 4 = life-threatening; 5 = fatal. |
| Percentage of Participants Who Developed Antibodies to ABP 501 | Up to week 72 | Two validated assays were used to detect the presence of anti-drug antibodies. All samples were first tested in an electrochemiluminescence (ECL)-based bridging immunoassay to detect anti-drug antibodies against ABP 501 (Binding Antibody Assay). Samples confirmed to be positive for binding antibodies were subsequently tested in a non-cell based bioassay to determine neutralizing activity against ABP 501. If a sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the sample was defined as positive for neutralizing antibodies. Preexisting antibody positive indicates participants with a positive result at baseline of the extension study. Developing antibody positive indicates participants with a negative or no result at baseline of the extension study who were positive at any time point post-baseline during the extension study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With an American College of Rheumatology (ACR) 20 Response | Parent study baseline, extension study baseline and weeks 4, 24, 48, and 70 | A participant was a responder if the following 3 criteria for improvement from Baseline of the parent study were met: * ≥ 20% improvement in tender joint count; * ≥ 20% improvement in swollen joint count; and * ≥ 20% improvement in at least 3 of the 5 following parameters: * Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); * Patient's global assessment of disease activity (measured on a likert scale from 0 to 10); * Physician's global assessment of disease activity (measured on a likert scale from 0 to 10); * Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index \[HAQ-DI\]); * C-Reactive Protein level. |
| Change From Parent Study Baseline in Disease Activity Score 28-C-reactive Protein (DAS28-CRP) | Parent study baseline, extension study baseline and weeks 4, 24, 48 and 70 | The DAS28-CRP is a composite score to measure disease activity in patients with rheumatoid arthritis, derived from the following variables: * The number of swollen and tender joints assessed using the 28-joint count; * C-reactive protein (CRP) level * Patient's global assessment of disease activity assessed on a score from 0 to 100 transformed from the result measured on a horizontal scale from 0 (no RA activity at all) to 10 (worst RA activity imaginable). The DAS28-CRP score ranges from approximately zero to ten. Higher DAS28-CRP scores indicate higher disease activity. |
Countries
Bulgaria, Canada, Czechia, Germany, Hungary, Poland, Romania, Russia, Spain, United Kingdom, United States
Participant flow
Recruitment details
This study was conducted at 83 centers in 11 countries in Eastern Europe, North America and Western Europe.
Pre-assignment details
Study 20130258 was a single-arm, open-label extension of the parent Study 20120262 (NCT01970475). Results are reported according to treatment in the parent Study 20120262.
Participants by arm
| Arm | Count |
|---|---|
| ABP 501/ABP 501 Participants who received ABP 501 in the parent study continued to receive ABP 501 40 mg subcutaneously (SC) every other week for an additional 18 months (total of 24-months treatment). | 230 |
| Adalimumab/ABP 501 Participants who received adalimumab in the parent study transitioned to receive ABP 501 40 mg subcutaneously every other week for 18 months. | 237 |
| Total | 467 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 6 |
| Overall Study | Lost to Follow-up | 3 | 3 |
| Overall Study | Other | 2 | 1 |
| Overall Study | Physician Decision | 1 | 2 |
| Overall Study | Withdrawal by Subject | 15 | 18 |
Baseline characteristics
| Characteristic | ABP 501/ABP 501 | Adalimumab/ABP 501 | Total |
|---|---|---|---|
| Age, Continuous | 54.7 years STANDARD_DEVIATION 11.71 | 56.1 years STANDARD_DEVIATION 11.4 | 55.4 years STANDARD_DEVIATION 11.56 |
| Age, Customized ≥ 65 years | 47 participants | 56 participants | 103 participants |
| Age, Customized Between 18 and 65 years | 183 participants | 181 participants | 364 participants |
| Geographic Region Eastern Europe | 153 participants | 156 participants | 309 participants |
| Geographic Region Latin America | 0 participants | 0 participants | 0 participants |
| Geographic Region North America | 65 participants | 62 participants | 127 participants |
| Geographic Region Western Europe | 12 participants | 19 participants | 31 participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Asian | 3 participants | 0 participants | 3 participants |
| Race/Ethnicity, Customized Black or African American | 8 participants | 12 participants | 20 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 27 participants | 19 participants | 46 participants |
| Race/Ethnicity, Customized Mixed Race | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Not Allowed to Collect | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 202 participants | 217 participants | 419 participants |
| Race/Ethnicity, Customized Other | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized White | 218 participants | 224 participants | 442 participants |
| Sex: Female, Male Female | 188 Participants | 191 Participants | 379 Participants |
| Sex: Female, Male Male | 42 Participants | 46 Participants | 88 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 72 / 229 | 71 / 237 |
| serious Total, serious adverse events | 25 / 229 | 21 / 237 |
Outcome results
Primary
Number of Participants With Adverse Events
Adverse events (AEs) were graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 according to the following scale: 1 = mild; 2 = moderate; 3 = severe; 4 = life-threatening; 5 = fatal. A treatment-related AE is defined as an event where the answer to the question is there a reasonable possibility that the event may have been caused by the Investigational Medicinal Product was yes. A serious adverse event is defined as an AE that meets at least 1 of the following serious criteria: * fatal * life threatening (places the subject at immediate risk of death) * requires inpatient hospitalization or prolongation of existing hospitalization * results in persistent or significant disability/incapacity * congenital anomaly/birth defect * other medically important serious event.
Time frame: From the first dose of study drug in the extension study to 28 days following the last dose; 72 weeks
Population: The safety analysis set included all participants enrolled and treated with at least 1 dose of ABP 501 in the extension study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ABP 501/ABP 501 | Number of Participants With Adverse Events | Any grade ≥ 3 adverse event | 26 participants |
| ABP 501/ABP 501 | Number of Participants With Adverse Events | Any serious adverse event (SAE) | 25 participants |
| ABP 501/ABP 501 | Number of Participants With Adverse Events | Any grade ≥ 3 treatment-related adverse event | 3 participants |
| ABP 501/ABP 501 | Number of Participants With Adverse Events | Any treatment-related serious adverse event | 2 participants |
| ABP 501/ABP 501 | Number of Participants With Adverse Events | Any adverse event (AE) | 143 participants |
| ABP 501/ABP 501 | Number of Participants With Adverse Events | Any AE leading to discontinuation of ABP 501 | 7 participants |
| ABP 501/ABP 501 | Number of Participants With Adverse Events | Any adverse event with outcome of death | 0 participants |
| ABP 501/ABP 501 | Number of Participants With Adverse Events | Any TRAE leading to discontinuation of ABP 501 | 4 participants |
| ABP 501/ABP 501 | Number of Participants With Adverse Events | Any treatment-related adverse event (TRAE) | 37 participants |
| ABP 501/ABP 501 | Number of Participants With Adverse Events | Any AE leading to discontinuation from study | 3 participants |
| ABP 501/ABP 501 | Number of Participants With Adverse Events | Any TRAE leading to discontinuation from study | 1 participants |
| ABP 501/ABP 501 | Number of Participants With Adverse Events | Any TRAE with an outcome of death | 0 participants |
| Adalimumab/ABP 501 | Number of Participants With Adverse Events | Any TRAE leading to discontinuation from study | 3 participants |
| Adalimumab/ABP 501 | Number of Participants With Adverse Events | Any adverse event (AE) | 154 participants |
| Adalimumab/ABP 501 | Number of Participants With Adverse Events | Any grade ≥ 3 adverse event | 16 participants |
| Adalimumab/ABP 501 | Number of Participants With Adverse Events | Any treatment-related adverse event (TRAE) | 43 participants |
| Adalimumab/ABP 501 | Number of Participants With Adverse Events | Any grade ≥ 3 treatment-related adverse event | 4 participants |
| Adalimumab/ABP 501 | Number of Participants With Adverse Events | Any adverse event with outcome of death | 0 participants |
| Adalimumab/ABP 501 | Number of Participants With Adverse Events | Any TRAE with an outcome of death | 0 participants |
| Adalimumab/ABP 501 | Number of Participants With Adverse Events | Any serious adverse event (SAE) | 21 participants |
| Adalimumab/ABP 501 | Number of Participants With Adverse Events | Any treatment-related serious adverse event | 1 participants |
| Adalimumab/ABP 501 | Number of Participants With Adverse Events | Any AE leading to discontinuation of ABP 501 | 10 participants |
| Adalimumab/ABP 501 | Number of Participants With Adverse Events | Any TRAE leading to discontinuation of ABP 501 | 5 participants |
| Adalimumab/ABP 501 | Number of Participants With Adverse Events | Any AE leading to discontinuation from study | 5 participants |
Primary
Number of Participants With Grade ≥ 3 Hematology and Chemistry Laboratory Results
Laboratory results were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 according to the following scale: 1 = mild; 2 = moderate; 3 = severe; 4 = life-threatening; 5 = fatal.
Time frame: From the first dose of study drug in the extension study to 28 days following the last dose; 72 weeks
Population: Safety analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ABP 501/ABP 501 | Number of Participants With Grade ≥ 3 Hematology and Chemistry Laboratory Results | Hemoglobin (anemia) | 1 participants |
| ABP 501/ABP 501 | Number of Participants With Grade ≥ 3 Hematology and Chemistry Laboratory Results | Bilirubin | 1 participants |
| ABP 501/ABP 501 | Number of Participants With Grade ≥ 3 Hematology and Chemistry Laboratory Results | Gamma glutamyl transferase | 7 participants |
| ABP 501/ABP 501 | Number of Participants With Grade ≥ 3 Hematology and Chemistry Laboratory Results | Alanine aminotransferase (ALT) | 1 participants |
| ABP 501/ABP 501 | Number of Participants With Grade ≥ 3 Hematology and Chemistry Laboratory Results | Potassium (hyperkalemia) | 1 participants |
| ABP 501/ABP 501 | Number of Participants With Grade ≥ 3 Hematology and Chemistry Laboratory Results | Aspartate aminotransferase (AST) | 1 participants |
| Adalimumab/ABP 501 | Number of Participants With Grade ≥ 3 Hematology and Chemistry Laboratory Results | Potassium (hyperkalemia) | 1 participants |
| Adalimumab/ABP 501 | Number of Participants With Grade ≥ 3 Hematology and Chemistry Laboratory Results | Aspartate aminotransferase (AST) | 0 participants |
| Adalimumab/ABP 501 | Number of Participants With Grade ≥ 3 Hematology and Chemistry Laboratory Results | Hemoglobin (anemia) | 0 participants |
| Adalimumab/ABP 501 | Number of Participants With Grade ≥ 3 Hematology and Chemistry Laboratory Results | Alanine aminotransferase (ALT) | 0 participants |
| Adalimumab/ABP 501 | Number of Participants With Grade ≥ 3 Hematology and Chemistry Laboratory Results | Bilirubin | 0 participants |
| Adalimumab/ABP 501 | Number of Participants With Grade ≥ 3 Hematology and Chemistry Laboratory Results | Gamma glutamyl transferase | 3 participants |
Primary
Percentage of Participants Who Developed Antibodies to ABP 501
Two validated assays were used to detect the presence of anti-drug antibodies. All samples were first tested in an electrochemiluminescence (ECL)-based bridging immunoassay to detect anti-drug antibodies against ABP 501 (Binding Antibody Assay). Samples confirmed to be positive for binding antibodies were subsequently tested in a non-cell based bioassay to determine neutralizing activity against ABP 501. If a sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the sample was defined as positive for neutralizing antibodies. Preexisting antibody positive indicates participants with a positive result at baseline of the extension study. Developing antibody positive indicates participants with a negative or no result at baseline of the extension study who were positive at any time point post-baseline during the extension study.
Time frame: Up to week 72
Population: The anti-drug antibody analysis set includes participants who received at least 1 dose of ABP 501 in the extension study and who had at least 1 evaluable antibody test assay against ABP 501 in the extension study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ABP 501/ABP 501 | Percentage of Participants Who Developed Antibodies to ABP 501 | Developing Binding Antibody Positive | 21.8 percentage of participants |
| ABP 501/ABP 501 | Percentage of Participants Who Developed Antibodies to ABP 501 | Preexisting Binding Antibody Positive | 32.3 percentage of participants |
| ABP 501/ABP 501 | Percentage of Participants Who Developed Antibodies to ABP 501 | Developing Neutralizing Antibody Positive | 8.7 percentage of participants |
| ABP 501/ABP 501 | Percentage of Participants Who Developed Antibodies to ABP 501 | Preexisting Neutralizing Antibody Positive | 5.7 percentage of participants |
| Adalimumab/ABP 501 | Percentage of Participants Who Developed Antibodies to ABP 501 | Developing Neutralizing Antibody Positive | 5.1 percentage of participants |
| Adalimumab/ABP 501 | Percentage of Participants Who Developed Antibodies to ABP 501 | Preexisting Binding Antibody Positive | 34.2 percentage of participants |
| Adalimumab/ABP 501 | Percentage of Participants Who Developed Antibodies to ABP 501 | Developing Binding Antibody Positive | 14.8 percentage of participants |
| Adalimumab/ABP 501 | Percentage of Participants Who Developed Antibodies to ABP 501 | Preexisting Neutralizing Antibody Positive | 8.9 percentage of participants |
Secondary
Change From Parent Study Baseline in Disease Activity Score 28-C-reactive Protein (DAS28-CRP)
The DAS28-CRP is a composite score to measure disease activity in patients with rheumatoid arthritis, derived from the following variables: * The number of swollen and tender joints assessed using the 28-joint count; * C-reactive protein (CRP) level * Patient's global assessment of disease activity assessed on a score from 0 to 100 transformed from the result measured on a horizontal scale from 0 (no RA activity at all) to 10 (worst RA activity imaginable). The DAS28-CRP score ranges from approximately zero to ten. Higher DAS28-CRP scores indicate higher disease activity.
Time frame: Parent study baseline, extension study baseline and weeks 4, 24, 48 and 70
Population: Full analysis set with available data at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ABP 501/ABP 501 | Change From Parent Study Baseline in Disease Activity Score 28-C-reactive Protein (DAS28-CRP) | Week 4 (n = 228, 235) | -2.40 units on a scale | Standard Deviation 1.322 |
| ABP 501/ABP 501 | Change From Parent Study Baseline in Disease Activity Score 28-C-reactive Protein (DAS28-CRP) | Week 48 (n = 216, 217) | -2.59 units on a scale | Standard Deviation 1.433 |
| ABP 501/ABP 501 | Change From Parent Study Baseline in Disease Activity Score 28-C-reactive Protein (DAS28-CRP) | Week 24 (n = 223, 227) | -2.49 units on a scale | Standard Deviation 1.272 |
| ABP 501/ABP 501 | Change From Parent Study Baseline in Disease Activity Score 28-C-reactive Protein (DAS28-CRP) | Week 70 (n = 205, 207) | -2.70 units on a scale | Standard Deviation 1.389 |
| ABP 501/ABP 501 | Change From Parent Study Baseline in Disease Activity Score 28-C-reactive Protein (DAS28-CRP) | Extension Study Baseline (n = 219, 221) | -2.26 units on a scale | Standard Deviation 1.255 |
| Adalimumab/ABP 501 | Change From Parent Study Baseline in Disease Activity Score 28-C-reactive Protein (DAS28-CRP) | Week 70 (n = 205, 207) | -2.51 units on a scale | Standard Deviation 1.445 |
| Adalimumab/ABP 501 | Change From Parent Study Baseline in Disease Activity Score 28-C-reactive Protein (DAS28-CRP) | Extension Study Baseline (n = 219, 221) | -2.25 units on a scale | Standard Deviation 1.289 |
| Adalimumab/ABP 501 | Change From Parent Study Baseline in Disease Activity Score 28-C-reactive Protein (DAS28-CRP) | Week 4 (n = 228, 235) | -2.32 units on a scale | Standard Deviation 1.257 |
| Adalimumab/ABP 501 | Change From Parent Study Baseline in Disease Activity Score 28-C-reactive Protein (DAS28-CRP) | Week 24 (n = 223, 227) | -2.33 units on a scale | Standard Deviation 1.316 |
| Adalimumab/ABP 501 | Change From Parent Study Baseline in Disease Activity Score 28-C-reactive Protein (DAS28-CRP) | Week 48 (n = 216, 217) | -2.51 units on a scale | Standard Deviation 1.414 |
Secondary
Percentage of Participants With an American College of Rheumatology (ACR) 20 Response
A participant was a responder if the following 3 criteria for improvement from Baseline of the parent study were met: * ≥ 20% improvement in tender joint count; * ≥ 20% improvement in swollen joint count; and * ≥ 20% improvement in at least 3 of the 5 following parameters: * Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); * Patient's global assessment of disease activity (measured on a likert scale from 0 to 10); * Physician's global assessment of disease activity (measured on a likert scale from 0 to 10); * Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index \[HAQ-DI\]); * C-Reactive Protein level.
Time frame: Parent study baseline, extension study baseline and weeks 4, 24, 48, and 70
Population: The full analysis set (all participants enrolled in the extension study) with available data at each time point
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ABP 501/ABP 501 | Percentage of Participants With an American College of Rheumatology (ACR) 20 Response | Week 4 (n = 228, 237) | 77.6 percentage of participants |
| ABP 501/ABP 501 | Percentage of Participants With an American College of Rheumatology (ACR) 20 Response | Week 48 (n = 216, 218) | 76.9 percentage of participants |
| ABP 501/ABP 501 | Percentage of Participants With an American College of Rheumatology (ACR) 20 Response | Week 24 (n = 223, 230) | 74.0 percentage of participants |
| ABP 501/ABP 501 | Percentage of Participants With an American College of Rheumatology (ACR) 20 Response | Week 70 (n = 206, 209) | 79.6 percentage of participants |
| ABP 501/ABP 501 | Percentage of Participants With an American College of Rheumatology (ACR) 20 Response | Extension study baseline (n = 228, 236) | 73.2 percentage of participants |
| Adalimumab/ABP 501 | Percentage of Participants With an American College of Rheumatology (ACR) 20 Response | Week 70 (n = 206, 209) | 78.0 percentage of participants |
| Adalimumab/ABP 501 | Percentage of Participants With an American College of Rheumatology (ACR) 20 Response | Extension study baseline (n = 228, 236) | 73.3 percentage of participants |
| Adalimumab/ABP 501 | Percentage of Participants With an American College of Rheumatology (ACR) 20 Response | Week 4 (n = 228, 237) | 77.6 percentage of participants |
| Adalimumab/ABP 501 | Percentage of Participants With an American College of Rheumatology (ACR) 20 Response | Week 24 (n = 223, 230) | 74.3 percentage of participants |
| Adalimumab/ABP 501 | Percentage of Participants With an American College of Rheumatology (ACR) 20 Response | Week 48 (n = 216, 218) | 78.4 percentage of participants |