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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02114931
Recruitment Status : Completed
First Posted : April 15, 2014
Results First Posted : April 24, 2017
Last Update Posted : April 24, 2017
Sponsor:
Information provided by (Responsible Party):
Amgen

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Arthritis, Rheumatoid
Intervention Biological: ABP 501
Enrollment 467
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.
Arm/Group Title ABP 501/ABP 501 Adalimumab/ABP 501
Hide Arm/Group Description 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). Participants who received adalimumab in the parent study transitioned to receive ABP 501 40 mg subcutaneously every other week for 18 months.
Period Title: Overall Study
Started 230 237
Received Treatment 229 [1] 237
Completed 205 207
Not Completed 25 30
Reason Not Completed
Withdrawal by Subject             15             18
Adverse Event             4             6
Lost to Follow-up             3             3
Physician Decision             1             2
Other             2             1
[1]
One participant was enrolled in error and did not receive treatment in the extension study
Arm/Group Title ABP 501/ABP 501 Adalimumab/ABP 501 Total
Hide Arm/Group Description 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). Participants who received adalimumab in the parent study transitioned to receive ABP 501 40 mg subcutaneously every other week for 18 months. Total of all reporting groups
Overall Number of Baseline Participants 230 237 467
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 230 participants 237 participants 467 participants
54.7  (11.71) 56.1  (11.40) 55.4  (11.56)
[1]
Measure Description: Age at baseline of parent study
Age, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 230 participants 237 participants 467 participants
Between 18 and 65 years 183 181 364
≥ 65 years 47 56 103
[1]
Measure Description: Age at baseline of parent study
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 230 participants 237 participants 467 participants
Female
188
  81.7%
191
  80.6%
379
  81.2%
Male
42
  18.3%
46
  19.4%
88
  18.8%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 230 participants 237 participants 467 participants
White 218 224 442
Black or African American 8 12 20
Asian 3 0 3
American Indian or Alaska Native 0 0 0
Native Hawaiian or Other Pacific Islander 0 0 0
Mixed Race 0 0 0
Other 1 1 2
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 230 participants 237 participants 467 participants
Hispanic or Latino 27 19 46
Not Hispanic or Latino 202 217 419
Not Allowed to Collect 1 1 2
Geographic Region  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 230 participants 237 participants 467 participants
Eastern Europe 153 156 309
Western Europe 12 19 31
North America 65 62 127
Latin America 0 0 0
1.Primary Outcome
Title Number of Participants With Adverse Events
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all participants enrolled and treated with at least 1 dose of ABP 501 in the extension study.
Arm/Group Title ABP 501/ABP 501 Adalimumab/ABP 501
Hide Arm/Group Description:
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).
Participants who received adalimumab in the parent study transitioned to receive ABP 501 40 mg subcutaneously every other week for 18 months.
Overall Number of Participants Analyzed 229 237
Measure Type: Number
Unit of Measure: participants
Any adverse event (AE) 143 154
Any grade ≥ 3 adverse event 26 16
Any treatment-related adverse event (TRAE) 37 43
Any grade ≥ 3 treatment-related adverse event 3 4
Any adverse event with outcome of death 0 0
Any TRAE with an outcome of death 0 0
Any serious adverse event (SAE) 25 21
Any treatment-related serious adverse event 2 1
Any AE leading to discontinuation of ABP 501 7 10
Any TRAE leading to discontinuation of ABP 501 4 5
Any AE leading to discontinuation from study 3 5
Any TRAE leading to discontinuation from study 1 3
2.Primary Outcome
Title Number of Participants With Grade ≥ 3 Hematology and Chemistry Laboratory Results
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title ABP 501/ABP 501 Adalimumab/ABP 501
Hide Arm/Group Description:
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).
Participants who received adalimumab in the parent study transitioned to receive ABP 501 40 mg subcutaneously every other week for 18 months.
Overall Number of Participants Analyzed 229 237
Measure Type: Number
Unit of Measure: participants
Hemoglobin (anemia) 1 0
Alanine aminotransferase (ALT) 1 0
Aspartate aminotransferase (AST) 1 0
Bilirubin 1 0
Gamma glutamyl transferase 7 3
Potassium (hyperkalemia) 1 1
3.Primary Outcome
Title Percentage of Participants Who Developed Antibodies to ABP 501
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title ABP 501/ABP 501 Adalimumab/ABP 501
Hide Arm/Group Description:
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).
Participants who received adalimumab in the parent study transitioned to receive ABP 501 40 mg subcutaneously every other week for 18 months.
Overall Number of Participants Analyzed 229 237
Measure Type: Number
Unit of Measure: percentage of participants
Preexisting Binding Antibody Positive 32.3 34.2
Preexisting Neutralizing Antibody Positive 5.7 8.9
Developing Binding Antibody Positive 21.8 14.8
Developing Neutralizing Antibody Positive 8.7 5.1
4.Secondary Outcome
Title Percentage of Participants With an American College of Rheumatology (ACR) 20 Response
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (all participants enrolled in the extension study) with available data at each time point
Arm/Group Title ABP 501/ABP 501 Adalimumab/ABP 501
Hide Arm/Group Description:
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).
Participants who received adalimumab in the parent study transitioned to receive ABP 501 40 mg subcutaneously every other week for 18 months.
Overall Number of Participants Analyzed 230 237
Measure Type: Number
Unit of Measure: percentage of participants
Extension study baseline (n = 228, 236) 73.2 73.3
Week 4 (n = 228, 237) 77.6 77.6
Week 24 (n = 223, 230) 74.0 74.3
Week 48 (n = 216, 218) 76.9 78.4
Week 70 (n = 206, 209) 79.6 78.0
5.Secondary Outcome
Title Change From Parent Study Baseline in Disease Activity Score 28-C-reactive Protein (DAS28-CRP)
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set with available data at each time point
Arm/Group Title ABP 501/ABP 501 Adalimumab/ABP 501
Hide Arm/Group Description:
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).
Participants who received adalimumab in the parent study transitioned to receive ABP 501 40 mg subcutaneously every other week for 18 months.
Overall Number of Participants Analyzed 230 237
Mean (Standard Deviation)
Unit of Measure: units on a scale
Extension Study Baseline (n = 219, 221) -2.26  (1.255) -2.25  (1.289)
Week 4 (n = 228, 235) -2.40  (1.322) -2.32  (1.257)
Week 24 (n = 223, 227) -2.49  (1.272) -2.33  (1.316)
Week 48 (n = 216, 217) -2.59  (1.433) -2.51  (1.414)
Week 70 (n = 205, 207) -2.70  (1.389) -2.51  (1.445)
Time Frame From the first dose of study drug in the extension study to 28 days following the last dose; 72 weeks
Adverse Event Reporting Description Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
 
Arm/Group Title ABP 501/ABP 501 Adalimumab/ABP 501
Hide Arm/Group Description 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). Participants who received adalimumab in the parent study transitioned to receive ABP 501 40 mg subcutaneously every other week for 18 months.
All-Cause Mortality
ABP 501/ABP 501 Adalimumab/ABP 501
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
ABP 501/ABP 501 Adalimumab/ABP 501
Affected / at Risk (%) Affected / at Risk (%)
Total   25/229 (10.92%)   21/237 (8.86%) 
Cardiac disorders     
Aortic valve stenosis  1  1/229 (0.44%)  0/237 (0.00%) 
Arteriosclerosis coronary artery  1  1/229 (0.44%)  0/237 (0.00%) 
Coronary artery disease  1  1/229 (0.44%)  0/237 (0.00%) 
Myocardial infarction  1  2/229 (0.87%)  0/237 (0.00%) 
Myocardial ischaemia  1  1/229 (0.44%)  0/237 (0.00%) 
Eye disorders     
Cataract  1  1/229 (0.44%)  2/237 (0.84%) 
Macular degeneration  1  0/229 (0.00%)  1/237 (0.42%) 
Retinal tear  1  0/229 (0.00%)  1/237 (0.42%) 
Gastrointestinal disorders     
Duodenal ulcer haemorrhage  1  1/229 (0.44%)  0/237 (0.00%) 
Gastric ulcer  1  0/229 (0.00%)  1/237 (0.42%) 
Gastrointestinal haemorrhage  1  0/229 (0.00%)  1/237 (0.42%) 
Haematochezia  1  0/229 (0.00%)  1/237 (0.42%) 
General disorders     
Device failure  1  0/229 (0.00%)  1/237 (0.42%) 
Hepatobiliary disorders     
Cholecystitis  1  1/229 (0.44%)  0/237 (0.00%) 
Infections and infestations     
Appendicitis  1  0/229 (0.00%)  1/237 (0.42%) 
Bronchitis  1  1/229 (0.44%)  0/237 (0.00%) 
Cystitis  1  1/229 (0.44%)  0/237 (0.00%) 
Device related infection  1  0/229 (0.00%)  1/237 (0.42%) 
Laryngitis  1  1/229 (0.44%)  0/237 (0.00%) 
Salpingitis  1  1/229 (0.44%)  0/237 (0.00%) 
Injury, poisoning and procedural complications     
Foot fracture  1  1/229 (0.44%)  0/237 (0.00%) 
Pubis fracture  1  0/229 (0.00%)  1/237 (0.42%) 
Ulna fracture  1  0/229 (0.00%)  1/237 (0.42%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  0/229 (0.00%)  1/237 (0.42%) 
Intervertebral disc degeneration  1  0/229 (0.00%)  1/237 (0.42%) 
Joint swelling  1  0/229 (0.00%)  1/237 (0.42%) 
Neck pain  1  1/229 (0.44%)  0/237 (0.00%) 
Osteoarthritis  1  2/229 (0.87%)  3/237 (1.27%) 
Osteoporotic fracture  1  0/229 (0.00%)  1/237 (0.42%) 
Rheumatoid arthritis  1  2/229 (0.87%)  0/237 (0.00%) 
Spinal column stenosis  1  0/229 (0.00%)  1/237 (0.42%) 
Spinal osteoarthritis  1  0/229 (0.00%)  1/237 (0.42%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Bladder cancer  1  0/229 (0.00%)  1/237 (0.42%) 
Colon cancer  1  1/229 (0.44%)  0/237 (0.00%) 
Diffuse large B-cell lymphoma  1  1/229 (0.44%)  0/237 (0.00%) 
Endometrial adenocarcinoma  1  1/229 (0.44%)  0/237 (0.00%) 
Nervous system disorders     
Carotid artery stenosis  1  0/229 (0.00%)  1/237 (0.42%) 
Headache  1  1/229 (0.44%)  0/237 (0.00%) 
Pregnancy, puerperium and perinatal conditions     
Abortion spontaneous  1  1/229 (0.44%)  0/237 (0.00%) 
Psychiatric disorders     
Anxiety  1  0/229 (0.00%)  1/237 (0.42%) 
Reproductive system and breast disorders     
Uterine cervical erosion  1  1/229 (0.44%)  0/237 (0.00%) 
Uterine polyp  1  1/229 (0.44%)  0/237 (0.00%) 
Uterine prolapse  1  1/229 (0.44%)  0/237 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Asthma  1  1/229 (0.44%)  0/237 (0.00%) 
Dyspnoea  1  1/229 (0.44%)  0/237 (0.00%) 
Surgical and medical procedures     
Bunion operation  1  0/229 (0.00%)  1/237 (0.42%) 
Prosthesis implantation  1  1/229 (0.44%)  0/237 (0.00%) 
Vascular disorders     
Accelerated hypertension  1  0/229 (0.00%)  1/237 (0.42%) 
Hypertensive crisis  1  0/229 (0.00%)  1/237 (0.42%) 
Raynaud's phenomenon  1  0/229 (0.00%)  1/237 (0.42%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
ABP 501/ABP 501 Adalimumab/ABP 501
Affected / at Risk (%) Affected / at Risk (%)
Total   72/229 (31.44%)   71/237 (29.96%) 
Infections and infestations     
Bronchitis  1  16/229 (6.99%)  13/237 (5.49%) 
Nasopharyngitis  1  18/229 (7.86%)  25/237 (10.55%) 
Pharyngitis  1  12/229 (5.24%)  7/237 (2.95%) 
Upper respiratory tract infection  1  18/229 (7.86%)  22/237 (9.28%) 
Musculoskeletal and connective tissue disorders     
Rheumatoid arthritis  1  11/229 (4.80%)  17/237 (7.17%) 
Vascular disorders     
Hypertension  1  16/229 (6.99%)  6/237 (2.53%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Amgen Inc.
Phone: 866-572-6436
Layout table for additonal information
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT02114931    
Other Study ID Numbers: 20130258
2013-004654-13 ( EudraCT Number )
First Submitted: April 11, 2014
First Posted: April 15, 2014
Results First Submitted: March 13, 2017
Results First Posted: April 24, 2017
Last Update Posted: April 24, 2017