Trial Outcomes & Findings for Long-term Safety and Efficacy of ABP 501 in Subjects With Moderate to Severe Rheumatoid Arthritis (NCT NCT02114931)

Last Updated: 2017-04-24

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

467 participants

Primary outcome timeframe

From the first dose of study drug in the extension study to 28 days following the last dose; 72 weeks

Results posted on

2017-04-24

Participant Flow

This study was conducted at 83 centers in 11 countries in Eastern Europe, North America and Western Europe.

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.

Participant milestones

Participant milestones
Measure	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).	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.
Overall Study STARTED	230	237
Overall Study Received Treatment	229	237
Overall Study COMPLETED	205	207
Overall Study NOT COMPLETED	25	30

Reasons for withdrawal

Reasons for withdrawal
Measure	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).	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.
Overall Study Withdrawal by Subject	15	18
Overall Study Adverse Event	4	6
Overall Study Lost to Follow-up	3	3
Overall Study Physician Decision	1	2
Overall Study Other	2	1

Baseline Characteristics

Long-term Safety and Efficacy of ABP 501 in Subjects With Moderate to Severe Rheumatoid Arthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ABP 501/ABP 501 n=230 Participants 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).	Adalimumab/ABP 501 n=237 Participants Participants who received adalimumab in the parent study transitioned to receive ABP 501 40 mg subcutaneously every other week for 18 months.	Total n=467 Participants Total of all reporting groups
Age, Continuous	54.7 years STANDARD_DEVIATION 11.71 • n=5 Participants	56.1 years STANDARD_DEVIATION 11.40 • n=7 Participants	55.4 years STANDARD_DEVIATION 11.56 • n=5 Participants
Age, Customized Between 18 and 65 years	183 participants n=5 Participants	181 participants n=7 Participants	364 participants n=5 Participants
Age, Customized ≥ 65 years	47 participants n=5 Participants	56 participants n=7 Participants	103 participants n=5 Participants
Sex: Female, Male Female	188 Participants n=5 Participants	191 Participants n=7 Participants	379 Participants n=5 Participants
Sex: Female, Male Male	42 Participants n=5 Participants	46 Participants n=7 Participants	88 Participants n=5 Participants
Race/Ethnicity, Customized White	218 participants n=5 Participants	224 participants n=7 Participants	442 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	8 participants n=5 Participants	12 participants n=7 Participants	20 participants n=5 Participants
Race/Ethnicity, Customized Asian	3 participants n=5 Participants	0 participants n=7 Participants	3 participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Race/Ethnicity, Customized Mixed Race	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Race/Ethnicity, Customized Other	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	27 participants n=5 Participants	19 participants n=7 Participants	46 participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	202 participants n=5 Participants	217 participants n=7 Participants	419 participants n=5 Participants
Race/Ethnicity, Customized Not Allowed to Collect	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Geographic Region Eastern Europe	153 participants n=5 Participants	156 participants n=7 Participants	309 participants n=5 Participants
Geographic Region Western Europe	12 participants n=5 Participants	19 participants n=7 Participants	31 participants n=5 Participants
Geographic Region North America	65 participants n=5 Participants	62 participants n=7 Participants	127 participants n=5 Participants
Geographic Region Latin America	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	ABP 501/ABP 501 n=229 Participants 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).	Adalimumab/ABP 501 n=237 Participants Participants who received adalimumab in the parent study transitioned to receive ABP 501 40 mg subcutaneously every other week for 18 months.
Number of Participants With Adverse Events Any grade ≥ 3 adverse event	26 participants	16 participants
Number of Participants With Adverse Events Any adverse event (AE)	143 participants	154 participants
Number of Participants With Adverse Events Any treatment-related adverse event (TRAE)	37 participants	43 participants
Number of Participants With Adverse Events Any grade ≥ 3 treatment-related adverse event	3 participants	4 participants
Number of Participants With Adverse Events Any adverse event with outcome of death	0 participants	0 participants
Number of Participants With Adverse Events Any TRAE with an outcome of death	0 participants	0 participants
Number of Participants With Adverse Events Any serious adverse event (SAE)	25 participants	21 participants
Number of Participants With Adverse Events Any treatment-related serious adverse event	2 participants	1 participants
Number of Participants With Adverse Events Any AE leading to discontinuation of ABP 501	7 participants	10 participants
Number of Participants With Adverse Events Any TRAE leading to discontinuation of ABP 501	4 participants	5 participants
Number of Participants With Adverse Events Any AE leading to discontinuation from study	3 participants	5 participants
Number of Participants With Adverse Events Any TRAE leading to discontinuation from study	1 participants	3 participants

PRIMARY outcome

Timeframe: From the first dose of study drug in the extension study to 28 days following the last dose; 72 weeks

Population: Safety analysis set

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.

Outcome measures

Outcome measures
Measure	ABP 501/ABP 501 n=229 Participants 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).	Adalimumab/ABP 501 n=237 Participants Participants who received adalimumab in the parent study transitioned to receive ABP 501 40 mg subcutaneously every other week for 18 months.
Number of Participants With Grade ≥ 3 Hematology and Chemistry Laboratory Results Hemoglobin (anemia)	1 participants	0 participants
Number of Participants With Grade ≥ 3 Hematology and Chemistry Laboratory Results Alanine aminotransferase (ALT)	1 participants	0 participants
Number of Participants With Grade ≥ 3 Hematology and Chemistry Laboratory Results Aspartate aminotransferase (AST)	1 participants	0 participants
Number of Participants With Grade ≥ 3 Hematology and Chemistry Laboratory Results Bilirubin	1 participants	0 participants
Number of Participants With Grade ≥ 3 Hematology and Chemistry Laboratory Results Gamma glutamyl transferase	7 participants	3 participants
Number of Participants With Grade ≥ 3 Hematology and Chemistry Laboratory Results Potassium (hyperkalemia)	1 participants	1 participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	ABP 501/ABP 501 n=229 Participants 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).	Adalimumab/ABP 501 n=237 Participants Participants who received adalimumab in the parent study transitioned to receive ABP 501 40 mg subcutaneously every other week for 18 months.
Percentage of Participants Who Developed Antibodies to ABP 501 Developing Binding Antibody Positive	21.8 percentage of participants	14.8 percentage of participants
Percentage of Participants Who Developed Antibodies to ABP 501 Preexisting Binding Antibody Positive	32.3 percentage of participants	34.2 percentage of participants
Percentage of Participants Who Developed Antibodies to ABP 501 Preexisting Neutralizing Antibody Positive	5.7 percentage of participants	8.9 percentage of participants
Percentage of Participants Who Developed Antibodies to ABP 501 Developing Neutralizing Antibody Positive	8.7 percentage of participants	5.1 percentage of participants

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	ABP 501/ABP 501 n=230 Participants 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).	Adalimumab/ABP 501 n=237 Participants Participants who received adalimumab in the parent study transitioned to receive ABP 501 40 mg subcutaneously every other week for 18 months.
Percentage of Participants With an American College of Rheumatology (ACR) 20 Response Extension study baseline (n = 228, 236)	73.2 percentage of participants	73.3 percentage of participants
Percentage of Participants With an American College of Rheumatology (ACR) 20 Response Week 4 (n = 228, 237)	77.6 percentage of participants	77.6 percentage of participants
Percentage of Participants With an American College of Rheumatology (ACR) 20 Response Week 24 (n = 223, 230)	74.0 percentage of participants	74.3 percentage of participants
Percentage of Participants With an American College of Rheumatology (ACR) 20 Response Week 48 (n = 216, 218)	76.9 percentage of participants	78.4 percentage of participants
Percentage of Participants With an American College of Rheumatology (ACR) 20 Response Week 70 (n = 206, 209)	79.6 percentage of participants	78.0 percentage of participants

SECONDARY outcome

Timeframe: Parent study baseline, extension study baseline and weeks 4, 24, 48 and 70

Population: Full analysis set with available data at each time point

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.

Outcome measures

Outcome measures
Measure	ABP 501/ABP 501 n=230 Participants 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).	Adalimumab/ABP 501 n=237 Participants Participants who received adalimumab in the parent study transitioned to receive ABP 501 40 mg subcutaneously every other week for 18 months.
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	-2.25 units on a scale Standard Deviation 1.289
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	-2.32 units on a scale Standard Deviation 1.257
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	-2.33 units on a scale Standard Deviation 1.316
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	-2.51 units on a scale Standard Deviation 1.414
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	-2.51 units on a scale Standard Deviation 1.445

Adverse Events

ABP 501/ABP 501

Serious events: 25 serious events

Other events: 72 other events

Deaths: 0 deaths

Adalimumab/ABP 501

Serious events: 21 serious events

Other events: 71 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	ABP 501/ABP 501 n=229 participants at risk 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).	Adalimumab/ABP 501 n=237 participants at risk Participants who received adalimumab in the parent study transitioned to receive ABP 501 40 mg subcutaneously every other week for 18 months.
Infections and infestations Bronchitis	7.0% 16/229 • From the first dose of study drug in the extension study to 28 days following the last dose; 72 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.5% 13/237 • From the first dose of study drug in the extension study to 28 days following the last dose; 72 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Nasopharyngitis	7.9% 18/229 • From the first dose of study drug in the extension study to 28 days following the last dose; 72 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	10.5% 25/237 • From the first dose of study drug in the extension study to 28 days following the last dose; 72 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Pharyngitis	5.2% 12/229 • From the first dose of study drug in the extension study to 28 days following the last dose; 72 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.0% 7/237 • From the first dose of study drug in the extension study to 28 days following the last dose; 72 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Upper respiratory tract infection	7.9% 18/229 • From the first dose of study drug in the extension study to 28 days following the last dose; 72 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	9.3% 22/237 • From the first dose of study drug in the extension study to 28 days following the last dose; 72 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	4.8% 11/229 • From the first dose of study drug in the extension study to 28 days following the last dose; 72 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	7.2% 17/237 • From the first dose of study drug in the extension study to 28 days following the last dose; 72 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Hypertension	7.0% 16/229 • From the first dose of study drug in the extension study to 28 days following the last dose; 72 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.5% 6/237 • From the first dose of study drug in the extension study to 28 days following the last dose; 72 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

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