Trial Outcomes & Findings for Efficacy and Safety Study of ABP 501 Compared to Adalimumab in Subjects With Moderate to Severe Rheumatoid Arthritis (NCT NCT01970475)

NCT ID: NCT01970475

Last Updated: 2016-12-13

Results Overview

A participant was a responder if the following 3 criteria for improvement from Baseline 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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

526 participants

Primary outcome timeframe

Baseline and Week 24

Results posted on

2016-12-13

Participant Flow

This study was conducted at 92 centers in 12 countries in Europe, North America and Latin America. The first participant enrolled on 24 October 2013 and the last participant enrolled on 26 May 2014.

Participants were randomized 1:1 to receive either ABP 501 or adalimumab at 40 mg every 2 weeks for 22 weeks. Randomization was stratified by geographic region and prior biologic use for rheumatoid arthritis (capped at 40% of the study population).

Participant milestones

Participant milestones
Measure	ABP 501 Participants received ABP 501 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22.	Adalimumab Participants received adalimumab 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22.
Overall Study STARTED	264	262
Overall Study COMPLETED	243	251
Overall Study NOT COMPLETED	21	11

Reasons for withdrawal

Reasons for withdrawal
Measure	ABP 501 Participants received ABP 501 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22.	Adalimumab Participants received adalimumab 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22.
Overall Study Withdrawal by Subject	11	6
Overall Study Adverse Event	7	3
Overall Study Lost to Follow-up	2	2
Overall Study Protocol Violation	1	0

Baseline Characteristics

Efficacy and Safety Study of ABP 501 Compared to Adalimumab in Subjects With Moderate to Severe Rheumatoid Arthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ABP 501 n=264 Participants Participants received ABP 501 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22.	Adalimumab n=262 Participants Participants received adalimumab 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22.	Total n=526 Participants Total of all reporting groups
Age, Continuous	55.4 years STANDARD_DEVIATION 11.88 • n=5 Participants	56.3 years STANDARD_DEVIATION 11.47 • n=7 Participants	55.9 years STANDARD_DEVIATION 11.67 • n=5 Participants
Age, Customized < 65 years	205 participants n=5 Participants	197 participants n=7 Participants	402 participants n=5 Participants
Age, Customized ≥ 65 years	59 participants n=5 Participants	65 participants n=7 Participants	124 participants n=5 Participants
Sex: Female, Male Female	214 Participants n=5 Participants	212 Participants n=7 Participants	426 Participants n=5 Participants
Sex: Female, Male Male	50 Participants n=5 Participants	50 Participants n=7 Participants	100 Participants n=5 Participants
Race/Ethnicity, Customized White	251 participants n=5 Participants	249 participants n=7 Participants	500 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	9 participants n=5 Participants	12 participants n=7 Participants	21 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 Other	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Ethnicity Hispanic or Latino	33 participants n=5 Participants	25 participants n=7 Participants	58 participants n=5 Participants
Ethnicity Not Hispanic or Latino	230 participants n=5 Participants	236 participants n=7 Participants	466 participants n=5 Participants
Ethnicity Not Allowed to Collect	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Geographic Region Eastern Europe	169 participants n=5 Participants	168 participants n=7 Participants	337 participants n=5 Participants
Geographic Region Western Europe	22 participants n=5 Participants	20 participants n=7 Participants	42 participants n=5 Participants
Geographic Region North America	72 participants n=5 Participants	72 participants n=7 Participants	144 participants n=5 Participants
Geographic Region Latin America	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants
Prior Biological Use for Rheumatoid Arthritis (RA) Yes	71 participants n=5 Participants	74 participants n=7 Participants	145 participants n=5 Participants
Prior Biological Use for Rheumatoid Arthritis (RA) No	193 participants n=5 Participants	188 participants n=7 Participants	381 participants n=5 Participants
Duration of RA	9.41 years STANDARD_DEVIATION 8.076 • n=5 Participants	9.37 years STANDARD_DEVIATION 8.047 • n=7 Participants	9.39 years STANDARD_DEVIATION 8.054 • n=5 Participants
Swollen Joint Count	14.7 swollen joints STANDARD_DEVIATION 9.05 • n=5 Participants	14.1 swollen joints STANDARD_DEVIATION 7.98 • n=7 Participants	14.4 swollen joints STANDARD_DEVIATION 8.53 • n=5 Participants
Tender Joint Count	24.3 tender joints STANDARD_DEVIATION 14.35 • n=5 Participants	23.9 tender joints STANDARD_DEVIATION 13.49 • n=7 Participants	24.1 tender joints STANDARD_DEVIATION 13.92 • n=5 Participants
Subject Global Health Assessment	6.5 units on a scale STANDARD_DEVIATION 1.92 • n=5 Participants	6.6 units on a scale STANDARD_DEVIATION 1.86 • n=7 Participants	6.5 units on a scale STANDARD_DEVIATION 1.89 • n=5 Participants
Investigator Global Health Assessment	6.8 units on a scale STANDARD_DEVIATION 1.29 • n=5 Participants	6.7 units on a scale STANDARD_DEVIATION 1.59 • n=7 Participants	6.8 units on a scale STANDARD_DEVIATION 1.45 • n=5 Participants
Subject's Assessment of Disease Related Pain	58.3 units on a scale STANDARD_DEVIATION 21.82 • n=5 Participants	60.6 units on a scale STANDARD_DEVIATION 22.37 • n=7 Participants	59.5 units on a scale STANDARD_DEVIATION 22.11 • n=5 Participants
Health Assessment Questionnaire-Disability Index (HAQ-DI)	1.4819 units on a scale STANDARD_DEVIATION 0.61715 • n=5 Participants	1.4976 units on a scale STANDARD_DEVIATION 0.64743 • n=7 Participants	1.4897 units on a scale STANDARD_DEVIATION 0.63186 • n=5 Participants
C-reactive Protein	13.881 mg/L STANDARD_DEVIATION 20.6870 • n=5 Participants	14.678 mg/L STANDARD_DEVIATION 19.3848 • n=7 Participants	14.278 mg/L STANDARD_DEVIATION 20.0338 • n=5 Participants
Disease Activity Score 28-C-Reactive Protein (DAS28-CRP)	5.66 units on a scale STANDARD_DEVIATION 0.918 • n=5 Participants	5.68 units on a scale STANDARD_DEVIATION 0.911 • n=7 Participants	5.67 units on a scale STANDARD_DEVIATION 0.914 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 24

Population: The full analysis set (all randomized participants); missing values were imputed using the last observation carried forward (LOCF) method for participants with at least 1 postbaseline value.

Outcome measures

Outcome measures
Measure	ABP 501 n=260 Participants Participants received ABP 501 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22.	Adalimumab n=261 Participants Participants received adalimumab 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22.
Percentage of Participants With an American College of Rheumatology (ACR) 20 Response at Week 24	74.6 percentage of participants	72.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline and weeks 2, 4, 8, 12, 18, and 24

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. A repeated measures analysis with the DAS28-CRP change from baseline as the response and the stratification variables, visit, treatment, treatment-by-visit interaction and the baseline DAS28-CRP measurement as predictors in the model was performed.

Outcome measures

Outcome measures
Measure	ABP 501 n=264 Participants Participants received ABP 501 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22.	Adalimumab n=262 Participants Participants received adalimumab 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22.
Change From Baseline in Disease Activity Score 28-C-reactive Protein (DAS28-CRP) Week 2 (n = 254, 252)	-1.01 units on a scale Standard Deviation 0.891	-0.96 units on a scale Standard Deviation 0.890
Change From Baseline in Disease Activity Score 28-C-reactive Protein (DAS28-CRP) Week 4 (n = 255, 254)	-1.45 units on a scale Standard Deviation 1.048	-1.42 units on a scale Standard Deviation 0.979
Change From Baseline in Disease Activity Score 28-C-reactive Protein (DAS28-CRP) Week 8 (n = 247, 255)	-1.79 units on a scale Standard Deviation 1.075	-1.70 units on a scale Standard Deviation 1.093
Change From Baseline in Disease Activity Score 28-C-reactive Protein (DAS28-CRP) Week 12 (n = 245, 250)	-2.04 units on a scale Standard Deviation 1.112	-1.93 units on a scale Standard Deviation 1.171
Change From Baseline in Disease Activity Score 28-C-reactive Protein (DAS28-CRP) Week 18 (n = 244, 250)	-2.30 units on a scale Standard Deviation 1.184	-2.17 units on a scale Standard Deviation 1.189
Change From Baseline in Disease Activity Score 28-C-reactive Protein (DAS28-CRP) Week 24 (n = 243, 250)	-2.32 units on a scale Standard Deviation 1.237	-2.32 units on a scale Standard Deviation 1.209

SECONDARY outcome

Timeframe: Baseline, week 2 and week 8

Population: Full analysis set; LOCF imputation was used for participants with at least 1 postbaseline value (indicated by n).

Outcome measures

Outcome measures
Measure	ABP 501 n=264 Participants Participants received ABP 501 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22.	Adalimumab n=262 Participants Participants received adalimumab 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22.
Percentage of Participants With an ACR20 Response at Week 2 and Week 8 Week 2 (n = 254, 257)	35.4 percentage of participants	24.5 percentage of participants
Percentage of Participants With an ACR20 Response at Week 2 and Week 8 Week 8 (n = 260, 261)	63.5 percentage of participants	62.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline and week 24

Population: Full analysis set with available data at week 24

A participant was a responder if the following 3 criteria for improvement from Baseline were met: * ≥ 50% improvement in tender joint count; * ≥ 50% improvement in swollen joint count; and * ≥ 50% 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 n=244 Participants Participants received ABP 501 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22.	Adalimumab n=252 Participants Participants received adalimumab 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22.
Percentage of Participants With an ACR50 Response at Week 24	49.2 percentage of participants	52.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Full analysis set with available data at week 24

A participant was a responder if the following 3 criteria for improvement from Baseline were met: * ≥ 70% improvement in tender joint count; * ≥ 70% improvement in swollen joint count; and * ≥ 70% 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 n=246 Participants Participants received ABP 501 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22.	Adalimumab n=253 Participants Participants received adalimumab 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22.
Percentage of Participants With an ACR70 Response at Week 24	26.0 percentage of participants	22.9 percentage of participants

SECONDARY outcome

Timeframe: From the time of first treatment up to 28 days following the last dose of study treatment; 26 weeks.

Population: The safety analysis set (all participants who received at least 1 dose of study drug)

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.

Outcome measures

Outcome measures
Measure	ABP 501 n=264 Participants Participants received ABP 501 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22.	Adalimumab n=262 Participants Participants received adalimumab 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22.
Number of Participants With Adverse Events Any adverse event (AE)	132 participants	143 participants
Number of Participants With Adverse Events Adverse event ≥ grade 3	9 participants	17 participants
Number of Participants With Adverse Events Treatment-related adverse event (TRAE)	50 participants	55 participants
Number of Participants With Adverse Events Treatment-related adverse event ≥ grade 3	3 participants	2 participants
Number of Participants With Adverse Events Serious adverse event (SAE)	10 participants	13 participants
Number of Participants With Adverse Events Treatment-related serious adverse event	4 participants	1 participants
Number of Participants With Adverse Events AE leading to discontinuation of study drug	5 participants	2 participants
Number of Participants With Adverse Events TRAE leading to discontinuation of study drug	4 participants	1 participants
Number of Participants With Adverse Events AE leading to discontinuation from study	7 participants	2 participants
Number of Participants With Adverse Events TRAE leading to discontinuation from study	5 participants	0 participants

SECONDARY outcome

Timeframe: Up to week 26

Population: Participants with at least 1 evaluable antibody test result (to either ABP 501 or adalimumab)

Two validated assays were used to detect the presence of anti-drug antibodies. Samples were first tested in an electrochemiluminescence (ECL)-based bridging immunoassay to detect anti-drug antibodies (ADA) against ABP 501 and adalimumab (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 or adalimumab (Neutralizing Antibody Assay). Developing antibody incidence is defined as a negative or no antibody result at baseline and a positive antibody result at a post-baseline time point.

Outcome measures

Outcome measures
Measure	ABP 501 n=264 Participants Participants received ABP 501 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22.	Adalimumab n=262 Participants Participants received adalimumab 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22.
Percentage of Participants Who Developed Antibodies to ABP 501 or Adalimumab Developing Binding Antibody	38.3 percentage of participants	38.2 percentage of participants
Percentage of Participants Who Developed Antibodies to ABP 501 or Adalimumab Developing Neutralizing Antibody	9.1 percentage of participants	11.1 percentage of participants

Adverse Events

ABP 501

Serious events: 10 serious events

Other events: 17 other events

Deaths: 0 deaths

Adalimumab

Serious events: 13 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	ABP 501 n=264 participants at risk Participants received ABP 501 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22.	Adalimumab n=262 participants at risk Participants received adalimumab 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22.
Infections and infestations Nasopharyngitis	6.4% 17/264 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	7.3% 19/262 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 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

Measure	ABP 501 n=264 participants at risk Participants received ABP 501 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22.	Adalimumab n=262 participants at risk Participants received adalimumab 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22.
Blood and lymphatic system disorders Lymphadenopathy	0.38% 1/264 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/262 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Acute myocardial infarction	0.00% 0/264 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.38% 1/262 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Cardiac failure congestive	0.00% 0/264 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.38% 1/262 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Cardiopulmonary failure	0.38% 1/264 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/262 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Arthritis bacterial	0.00% 0/264 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.38% 1/262 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Gastroenteritis	0.00% 0/264 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.38% 1/262 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Peritoneal abscess	0.38% 1/264 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/262 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Pneumonia	0.38% 1/264 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/262 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Pneumonia fungal	0.00% 0/264 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.38% 1/262 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Sepsis	0.76% 2/264 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/262 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Humerus fracture	0.38% 1/264 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/262 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Meniscus injury	0.38% 1/264 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/262 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Thoracic vertebral fracture	0.00% 0/264 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.38% 1/262 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Foot deformity	0.00% 0/264 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.38% 1/262 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/264 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.38% 1/262 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Myocardial infarction	0.00% 0/264 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.38% 1/262 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Wolff-Parkinson-White syndrome	0.00% 0/264 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.38% 1/262 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Enterocolitis	0.38% 1/264 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/262 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Large intestinal obstruction	0.00% 0/264 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.38% 1/262 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Immune system disorders Corneal graft rejection	0.00% 0/264 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.38% 1/262 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Immune system disorders Hypersensitivity	0.38% 1/264 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/262 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Appendicitis perforated	0.38% 1/264 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/262 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Pseudarthrosis	0.00% 0/264 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.38% 1/262 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Cerebrovascular accident	0.38% 1/264 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/262 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Hypertension	0.38% 1/264 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/262 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Venous thrombosis limb	0.38% 1/264 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/262 • From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.