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A Study to Compare FKB327 Efficacy and Safety With Humira® in Rheumatoid Arthritis Patients (ARABESC)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02260791
First Posted: October 9, 2014
Last Update Posted: October 20, 2017
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.
Information provided by (Responsible Party):
Fujifilm Kyowa Kirin Biologics Co., Ltd.
Results First Submitted: July 5, 2017  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Arthritis, Rheumatoid
Interventions: Drug: FKB327
Drug: Humira®

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Patients were enrolled in 109 sites in 12 countries in 3 geographical regions: North America, Europe and Rest of World. The first participant enrolled on 05 January 2015 and the last participant completed on 12 July 2016.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

Screening details:

Patients were randomised in a 1:1 ratio to receive either FKB327 40 mg eow or Humira 40 mg eow using the following stratification factors: prior biological treatment for Rheumatoid Arthritis (RA) (yes/no) and Screening disease activity (DAS28-CRP ≤5.1/>5.1).


Reporting Groups
  Description
FKB327 Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks.
Humira® Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks.

Participant Flow:   Overall Study
    FKB327   Humira®
STARTED   366   362 
COMPLETED   333   328 
NOT COMPLETED   33   34 
Lost to Follow-up                4                4 
Lack of Efficacy                2                1 
Adverse Event                13                9 
Death                1                0 
Withdrawal by Subject                11                16 
Screen failure                0                1 
Protocol deviation                2                3 



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Safety Analysis Set was defined as the set of patients who received at least 1 dose of randomised treatment.

Reporting Groups
  Description
FKB327 Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks.
Humira® Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks.
Total Total of all reporting groups

Baseline Measures
   FKB327   Humira®   Total 
Overall Participants Analyzed 
[Units: Participants]
 366   362   728 
Age 
[Units: Years]
Mean (Full Range)
 53 
 (18 to 85) 
 53.6 
 (21 to 93) 
 53.3 
 (18 to 93) 
Age, Customized 
[Units: Participants]
Count of Participants
     
<18 years   0   0   0 
Between 18 and 65 years   302   299   601 
>65 years   64   63   127 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      281  76.8%      284  78.5%      565  77.6% 
Male      85  23.2%      78  21.5%      163  22.4% 
Race (NIH/OMB) 
[Units: Participants]
Count of Participants
     
American Indian or Alaska Native      1   0.3%      1   0.3%      2   0.3% 
Asian      1   0.3%      1   0.3%      2   0.3% 
Native Hawaiian or Other Pacific Islander      0   0.0%      0   0.0%      0   0.0% 
Black or African American      2   0.5%      4   1.1%      6   0.8% 
White      311  85.0%      308  85.1%      619  85.0% 
More than one race      0   0.0%      0   0.0%      0   0.0% 
Unknown or Not Reported      51  13.9%      48  13.3%      99  13.6% 
Region of Enrollment 
[Units: Participants]
     
Canada   3   4   7 
Romania   15   13   28 
United States   39   39   78 
Czech Republic   33   34   67 
Ukraine   56   58   114 
Poland   67   67   134 
Bulgaria   7   7   14 
Chile   20   21   41 
Peru   51   49   100 
Germany   14   12   26 
Spain   4   6   10 
Russia   57   52   109 


  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   American College of Rheumatology (ACR) 20 Response Rate   [ Time Frame: Week 24 ]

Measure Type Primary
Measure Title American College of Rheumatology (ACR) 20 Response Rate
Measure Description

The primary efficacy endpoint was the ACR20 response rate at Week 24.

An ACR20 response meant that the patient achieved a 20% improvement in Tender Joint Count and Swollen Joint Count and in at least 3 of the other 5 Core Data Set elements listed below.

  • Acute phase reactant (CRP)
  • Patient global assessment of disease activity
  • Physician global assessment of disease activity
  • Patient pain scale
  • Disability/functional questionnaire (patient completed Health Assessment Questionnaire Disability Index [HAQ-DI])
Time Frame Week 24  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Full Analysis Set (FAS) was defined as the set of patients who received at least 1 dose of the randomised treatment and who had at least 1 evaluable primary efficacy measurement after their first dose of randomised treatment. Patients were analysed according to the randomised treatment in the primary analysis.

Reporting Groups
  Description
FKB327 Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks.
Humira® Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks.

Measured Values
   FKB327   Humira® 
Participants Analyzed 
[Units: Participants]
 363   358 
American College of Rheumatology (ACR) 20 Response Rate 
[Units: Percentage of participants]
Number (95% Confidence Interval)
 72.5 
 (67.5 to 77.0) 
 74.3 
 (69.4 to 78.8) 


Statistical Analysis 1 for American College of Rheumatology (ACR) 20 Response Rate
Groups [1] All groups
Statistical Test Type [2] Equivalence
Mean Difference (Final Values) [3] -1.8
90% Confidence Interval -7.3 to 3.6
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The difference and its 90% Confidence Interval (CI) for primary endpoint between FKB327 and Humira were estimated. If the 90% CI fell entirely between pre-specified equivalence margin (-12% to +15%), then FKB327 was considered equivalent to Humira.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  -12% to +15% equivalence margin using 90% CI around the difference in ACR20 response rate
[3] Other relevant estimation information:
  No text entered.



2.  Secondary:   Disease Activity Score 28 (DAS28) Based on C-reactive Protein (DAS28-CRP) Score   [ Time Frame: Week 24 ]

Measure Type Secondary
Measure Title Disease Activity Score 28 (DAS28) Based on C-reactive Protein (DAS28-CRP) Score
Measure Description The DAS28-CRP assessment involved evaluating the number of tender (TJC) and swollen (SJC) joints (out of 28 specified joints), serum CRP, and patient global assessment of disease activity (VAS from 0 to 100, very well to extremely bad). The DAS28-CRP is a number on a scale from 0 to 10 indicating the current activity of the patient’s RA. A higher score indicates higher disease activity.
Time Frame Week 24  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Full Analysis Set (FAS) was defined as the set of patients who received at least 1 dose of the randomised treatment and who had at least 1 evaluable primary efficacy measurement after their first dose of randomised treatment. Patients were analysed according to the randomised treatment in the primary analysis.

Reporting Groups
  Description
FKB327 Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks.
Humira® Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks.

Measured Values
   FKB327   Humira® 
Participants Analyzed 
[Units: Participants]
 363   358 
Disease Activity Score 28 (DAS28) Based on C-reactive Protein (DAS28-CRP) Score 
[Units: Units on a scale]
Mean (Standard Deviation)
   
Baseline (number analyzed = 362, 358)   6.05  (0.913)   6.06  (0.852) 
Week 2 (number analyzed = 361, 351)   4.92  (1.070)   4.86  (1.203) 
Week 4 (number analyzed = 357, 348)   4.44  (1.317)   4.43  (1.383) 
Week 8 (number analyzed = 348, 345)   4.11  (1.295)   4.09  (1.397) 
Week 12 (number analyzed = 351, 340)   3.81  (1.320)   3.85  (1.339) 
Week 16 (number analyzed = 350, 341)   3.68  (1.304)   3.67  (1.419) 
Week 20 (number analyzed = 344, 336)   3.58  (1.329)   3.57  (1.388) 
Week 24 (number analyzed = 340, 339)   3.47  (1.298)   3.47  (1.336) 


Statistical Analysis 1 for Disease Activity Score 28 (DAS28) Based on C-reactive Protein (DAS28-CRP) Score
Groups [1] All groups
Statistical Test Type [2] Equivalence
Difference in least square mean [3] 0.01
95% Confidence Interval -0.16 to 0.18
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The secondary hypothesis involved equivalence of the difference between FKB327 and Humira in DAS28-CRP at Week 24. Based on the repeated measures analysis model, the difference and its 95% CI in the least-squares means (LSMs) for DAS28-CRP at Week 24 between FKB327 and Humira were estimated. If the 95% CI fell entirely between the pre-specified margin (+/- 0.6), then FKB327 was considered equivalent to Humira.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  If the 2-sided 95% CI for the difference in DAS28-CRP at Week 24 between FKB327 and Humira fell entirely between −0.6 and +0.6 then FKB327 was considered equivalent to Humira.
[3] Other relevant estimation information:
  No text entered.



3.  Secondary:   ACR20 Response Rates Over Time   [ Time Frame: Week 24 ]

Measure Type Secondary
Measure Title ACR20 Response Rates Over Time
Measure Description

An ACR20 response meant that the patient achieved a 20% improvement in Tender Joint Count and Swollen Joint Count and in at least 3 of the other 5 Core Data Set elements listed below.

  • Acute phase reactant (CRP)
  • Patient global assessment of disease activity
  • Physician global assessment of disease activity
  • Patient pain scale
  • Disability/functional questionnaire (patient completed Health Assessment Questionnaire Disability Index [HAQ-DI])
Time Frame Week 24  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Full Analysis Set (FAS) was defined as the set of patients who received at least 1 dose of the randomised treatment and who had at least 1 evaluable primary efficacy measurement after their first dose of randomised treatment.Patients were analysed according to the randomised treatment in the primary analysis.

Reporting Groups
  Description
FKB327 Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks.
Humira® Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks.

Measured Values
   FKB327   Humira® 
Participants Analyzed 
[Units: Participants]
 363   358 
ACR20 Response Rates Over Time 
[Units: Percentage of responders]
Number (95% Confidence Interval)
   
Week 2 (number analyzed = 362, 352)   37.3 
 (32.3 to 42.5) 
 31 
 (26.2 to 36.1) 
Week 4 (number analyzed = 359, 349)   51 
 (45.7 to 56.3) 
 52.4 
 (47.1 to 57.8) 
Week 8 (number analyzed = 353, 347)   64.6 
 (59.4 to 69.6) 
 67.7 
 (62.5 to 72.6) 
Week 12 (number analyzed = 351, 342)   69.2 
 (64.1 to 74) 
 72.2 
 (67.2 to 76.9) 
Week 16 (number analyzed = 350, 342)   74.6 
 (69.7 to 79.1) 
 74.9 
 (69.9 to 79.4) 
Week 20 (number analyzed = 345, 338)   78 
 (73.2 to 82.2) 
 77.8 
 (73 to 82.1) 
Week 24 (number analyzed = 341, 338)   77.1 
 (72.3 to 81.5) 
 79.3 
 (74.6 to 83.5) 

No statistical analysis provided for ACR20 Response Rates Over Time



4.  Secondary:   ACR50 Response Rates Over Time   [ Time Frame: Week 24 ]

Measure Type Secondary
Measure Title ACR50 Response Rates Over Time
Measure Description

An ACR50 response meant that the patient achieved a 50% improvement in Tender Joint Count and Swollen Joint Count and in at least 3 of the other 5 Core Data Set elements listed below.

  • Acute phase reactant (CRP)
  • Patient global assessment of disease activity
  • Physician global assessment of disease activity
  • Patient pain scale
  • Disability/functional questionnaire (patient completed Health AssessmentQuestionnaire Disability Index [HAQ-DI])
Time Frame Week 24  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Full Analysis Set (FAS) was defined as the set of patients who received at least 1 dose of the randomised treatment and who had at least 1 evaluable primary efficacy measurement after their first dose of randomised treatment. Patients were analysed according to the randomised treatment in the primary analysis.

Reporting Groups
  Description
FKB327 Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks.
Humira® Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks.

Measured Values
   FKB327   Humira® 
Participants Analyzed 
[Units: Participants]
 363   358 
ACR50 Response Rates Over Time 
[Units: Percentage of responders]
Number (95% Confidence Interval)
   
Week 2 (number analyzed = 362, 352)   5 
 (3 to 7.7) 
 8.8 
 (6.1 to 12.3) 
Week 4 (number analyzed = 359, 349)   17.3 
 (13.5 to 21.6) 
 17.8 
 (13.9 to 22.2) 
Week 8 (number analyzed = 353, 346)   28.9 
 (24.2 to 33.9) 
 30.9 
 (26.1 to 36.1) 
Week 12 (number analyzed = 351, 342)   37.6 
 (32.5 to 42.9) 
 35.1 
 (30 to 40.4) 
Week 16 (number analyzed = 350, 342)   39.4 
 (34.3 to 44.8) 
 44.7 
 (39.4 to 50.2) 
Week 20 (number analyzed = 345, 339)   45.5 
 (40.2 to 50.9) 
 46 
 (40.6 to 51.5) 
Week 24 (number analyzed = 341, 338)   49 
 (43.6 to 54.4) 
 49.4 
 (44 to 54.9) 

No statistical analysis provided for ACR50 Response Rates Over Time



5.  Secondary:   ACR70 Response Rates Over Time   [ Time Frame: Week 24 ]

Measure Type Secondary
Measure Title ACR70 Response Rates Over Time
Measure Description

An ACR70 response meant that the patient achieved a 70% improvement in Tender Joint Count and Swollen Joint Count and in at least 3 of the other 5 Core Data Set elements listed below.

  • Acute phase reactant (CRP)
  • Patient global assessment of disease activity
  • Physician global assessment of disease activity
  • Patient pain scale
  • Disability/functional questionnaire (patient completed Health AssessmentQuestionnaire Disability Index [HAQ-DI])
Time Frame Week 24  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Full Analysis Set (FAS) was defined as the set of patients who received at least 1 dose of the randomised treatment and who had at least 1 evaluable primary efficacy measurement after their first dose of randomised treatment. Patients were analysed according to the randomised treatment in the primary analysis.

Reporting Groups
  Description
FKB327 Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks.
Humira® Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks.

Measured Values
   FKB327   Humira® 
Participants Analyzed 
[Units: Participants]
 363   358 
ACR70 Response Rates Over Time 
[Units: Percentage of responders]
Number (95% Confidence Interval)
   
Week 2 (number analyzed = 362, 352)   0.3 
 (0 to 1.5) 
 2.3 
 (1 to 4.4) 
Week 4 (number analyzed = 359, 349)   4.5 
 (2.6 to 7.1) 
 6.9 
 (4.5 to 10.1) 
Week 8 (number analyzed = 353, 347)   11.3 
 (8.2 to 15.1) 
 10.7 
 (7.6 to 14.4) 
Week 12 (number analyzed = 351, 342)   15.4 
 (11.8 to 19.6) 
 13.2 
 (9.8 to 17.2) 
Week 16 (number analyzed = 350, 342)   17.4 
 (13.6 to 21.8) 
 19 
 (15 to 23.6) 
Week 20 (number analyzed = 345, 339)   20.9 
 (16.7 to 25.5) 
 23.6 
 (19.2 to 28.5) 
Week 24 (number analyzed = 342, 338)   21.3 
 (17.1 to 26.1) 
 25.1 
 (20.6 to 30.1) 

No statistical analysis provided for ACR70 Response Rates Over Time



6.  Secondary:   Swollen Joint Count   [ Time Frame: Week 24 ]

Measure Type Secondary
Measure Title Swollen Joint Count
Measure Description Counts of swollen joints from amongst 66 selected joints performed by a trained and qualified joint assessor using standardised techniques recommended by the European League Against Rheumatism (EULAR). Joints were classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 66 with higher scores indicating severe disease. Swollen joint count is a value of the individual ACR core set variables.
Time Frame Week 24  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Full Analysis Set (FAS) was defined as the set of patients who received at least 1 dose of the randomised treatment and who had at least 1 evaluable primary efficacy measurement after their first dose of randomised treatment. Patients were analysed according to the randomised treatment in the primary analysis.

Reporting Groups
  Description
FKB327 Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks.
Humira® Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks.

Measured Values
   FKB327   Humira® 
Participants Analyzed 
[Units: Participants]
 363   358 
Swollen Joint Count 
[Units: Count / Score]
Mean (Standard Deviation)
   
Baseline   16.3  (9.1)   16  (8.96) 
Week 24   3.8  (6.04)   3.5  (5.23) 

No statistical analysis provided for Swollen Joint Count



7.  Secondary:   Tender Joint Count   [ Time Frame: Week 24 ]

Measure Type Secondary
Measure Title Tender Joint Count
Measure Description Counts of tender joints from amongst 68 selected joints were performed by a trained and qualified joint assessor using standardised techniques recommended by the European League Against Rheumatism (EULAR). Joints were classified as tender/not tender giving a total possible tender joint count score of 0 to 68 with higher scores indicating severe disease.Tender joint count is a value of the individual ACR core set variables.
Time Frame Week 24  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Full Analysis Set (FAS) was defined as the set of patients who received at least 1 dose of the randomised treatment and who had at least 1 evaluable primary efficacy measurement after their first dose of randomised treatment. Patients were analysed according to the randomised treatment in the primary analysis.

Reporting Groups
  Description
FKB327 Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks.
Humira® Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks.

Measured Values
   FKB327   Humira® 
Participants Analyzed 
[Units: Participants]
 363   358 
Tender Joint Count 
[Units: Count / Score]
Mean (Standard Deviation)
   
Baseline   26.2  (14.49)   25.9  (14.52) 
Week 24   8.5  (10.56)   8.1  (9.36) 

No statistical analysis provided for Tender Joint Count



8.  Secondary:   Analysis of Serum C-Reactive Protein (CRP) Concentration   [ Time Frame: Week 24 ]

Measure Type Secondary
Measure Title Analysis of Serum C-Reactive Protein (CRP) Concentration
Measure Description Analysis of serum C-Reactive Protein (CRP) concentrations for inclusion in the ACR20/50/70 and DAS28-CRP scores was performed by a central laboratory. Elevation of CRP is a nonspecific marker of inflammation. Values above 10 mg/L were considered to be abnormally high. Decrease in level of CRP indicates reduction in inflammation.
Time Frame Week 24  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Full Analysis Set (FAS) was defined as the set of patients who received at least 1 dose of the randomised treatment and who had at least 1 evaluable primary efficacy measurement after their first dose of randomised treatment. Patients were analysed according to the randomised treatment in the primary analysis.

Reporting Groups
  Description
FKB327 Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks.
Humira® Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks.

Measured Values
   FKB327   Humira® 
Participants Analyzed 
[Units: Participants]
 363   358 
Analysis of Serum C-Reactive Protein (CRP) Concentration 
[Units: mg/L]
Mean (Standard Deviation)
   
Baseline   25.12  (26.746)   26.73  (28.534) 
Week 24   10.98  (16.819)   11.78  (18.528) 

No statistical analysis provided for Analysis of Serum C-Reactive Protein (CRP) Concentration



9.  Secondary:   Patient Assessment of Disease Activity   [ Time Frame: Week 24 ]

Measure Type Secondary
Measure Title Patient Assessment of Disease Activity
Measure Description Patient assessment of disease activity visual analogue scale (VAS) will be assessed on 100-point scales (ranging from very well (0) to extremely bad (100)).The patient assessment of disease activity VAS will contribute to the calculation of the DAS28 score. The patient assessment of disease activity VAS will contribute to the calculation of ACR20, ACR50 and ACR70 response.
Time Frame Week 24  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Full Analysis Set (FAS) was defined as the set of patients who received at least 1 dose of the randomised treatment and who had at least 1 evaluable primary efficacy measurement after their first dose of randomised treatment. Patients were analysed according to the randomised treatment in the primary analysis.

Reporting Groups
  Description
FKB327 Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks.
Humira® Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks.

Measured Values
   FKB327   Humira® 
Participants Analyzed 
[Units: Participants]
 363   358 
Patient Assessment of Disease Activity 
[Units: Units on a scale]
Mean (Standard Deviation)
   
Baseline   68  (17.98)   68.2  (18.18) 
Week 24   35.2  (24.04)   33.2  (23.4) 

No statistical analysis provided for Patient Assessment of Disease Activity



10.  Secondary:   Physician Assessment of Disease Activity   [ Time Frame: Week 24 ]

Measure Type Secondary
Measure Title Physician Assessment of Disease Activity
Measure Description Physician assessment of disease activity visual analogue scale (VAS) will be assessed on 100-point scale (ranging from very low (0) to very high (100)). The physician assessment of disease activity VAS will contribute to the calculation of ACR20, ACR50 and ACR70 response.
Time Frame Week 24  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Full Analysis Set (FAS) was defined as the set of patients who received at least 1 dose of the randomised treatment and who had at least 1 evaluable primary efficacy measurement after their first dose of randomised treatment. Patients were analysed according to the randomised treatment in the primary analysis.

Reporting Groups
  Description
FKB327 Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks.
Humira® Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks.

Measured Values
   FKB327   Humira® 
Participants Analyzed 
[Units: Participants]
 363   358 
Physician Assessment of Disease Activity 
[Units: Units on a scale]
Mean (Standard Deviation)
   
Baseline   68.4  (14.58)   66.2  (15.48) 
Week 24   21.5  (17.29)   21.5  (16.97) 

No statistical analysis provided for Physician Assessment of Disease Activity



11.  Secondary:   Patient's Assessment of Pain   [ Time Frame: Week 24 ]

Measure Type Secondary
Measure Title Patient's Assessment of Pain
Measure Description An injection site pain visual analogue score (VAS) will be administered to the patient. To determine the extent of the pain, patients will be asked to place a small vertical mark on a horizontal scale from 0 to 100, the ends of which are labelled with the extreme responses to be measured (“No pain” at 0 and “Intolerable pain” at 100). Patient's assessment of pain is a value of the individual ACR core set variables.
Time Frame Week 24  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Full Analysis Set (FAS) was defined as the set of patients who received at least 1 dose of the randomised treatment and who had at least 1 evaluable primary efficacy measurement after their first dose of randomised treatment. Patients were analysed according to the randomised treatment in the primary analysis.

Reporting Groups
  Description
FKB327 Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks.
Humira® Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks.

Measured Values
   FKB327   Humira® 
Participants Analyzed 
[Units: Participants]
 363   358 
Patient's Assessment of Pain 
[Units: Units on a scale]
Mean (Standard Deviation)
   
Baseline   66.8  (18.71)   67.7  (18.56) 
Week 24   34.7  (23.86)   33.6  (23.86) 

No statistical analysis provided for Patient's Assessment of Pain



12.  Secondary:   Health Assessment Questionnaire Disability Index (HAQ-DI)   [ Time Frame: Week 24 ]

Measure Type Secondary
Measure Title Health Assessment Questionnaire Disability Index (HAQ-DI)
Measure Description The HAQ-DI is a 20-question, self-administered instrument that measures the patient's functional ability on a 4-level difficulty scale (0 to 3, with 0 representing normal or no difficulty and 3 representing inability to perform). Eight categories of functioning are included: dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. This scale is sensitive to change and is a good predictor of future disability. HAQ-DI is a value of the individual ACR core set variables.
Time Frame Week 24  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Full Analysis Set (FAS) was defined as the set of patients who received at least 1 dose of the randomised treatment and who had at least 1 evaluable primary efficacy measurement after their first dose of randomised treatment. Patients were analysed according to the randomised treatment in the primary analysis.

Reporting Groups
  Description
FKB327 Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks.
Humira® Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks.

Measured Values
   FKB327   Humira® 
Participants Analyzed 
[Units: Participants]
 363   358 
Health Assessment Questionnaire Disability Index (HAQ-DI) 
[Units: Units on a scale]
Mean (Standard Deviation)
   
Baseline   1.78  (0.544)   1.8  (0.538) 
Week 24   1.21  (0.696)   1.26  (0.719) 

No statistical analysis provided for Health Assessment Questionnaire Disability Index (HAQ-DI)



13.  Secondary:   DAS28-CRP Score Over Time   [ Time Frame: Baseline and Week 24 ]

Measure Type Secondary
Measure Title DAS28-CRP Score Over Time
Measure Description The DAS28 score is a combined index that has been developed to measure the disease activity in patients with RA and has been extensively validated for its use in clinical studies. The DAS28-CRP assessment involved evaluating the number of tender (TJC) and swollen (SJC) joints (out of 28 specified joints), serum CRP, and patient global assessment of disease activity (VAS from 0 to 100, very well to extremely bad). The individual results are summed using a formula. The DAS28 is a number on a scale from 0 to 10 indicating the current activity of the patient's RA. A higher score indicates higher disease activity.
Time Frame Baseline and Week 24  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Full Analysis Set (FAS) was defined as the set of patients who received at least 1 dose of the randomised treatment and who had at least 1 evaluable primary efficacy measurement after their first dose of randomised treatment. Patients were analysed according to the randomised treatment in the primary analysis.

Reporting Groups
  Description
FKB327 Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks.
Humira® Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks.

Measured Values
   FKB327   Humira® 
Participants Analyzed 
[Units: Participants]
 363   358 
DAS28-CRP Score Over Time 
[Units: Units on a scale]
Mean (Standard Deviation)
   
Baseline (number analyzed = 362, 358)   6.05  (0.913)   6.06  (0.852) 
Week 24 (number analyzed = 340, 339)   3.47  (1.298)   3.47  (1.336) 

No statistical analysis provided for DAS28-CRP Score Over Time



14.  Secondary:   DAS28 Score Based on Erythrocyte Sedimentation Rate (DAS28-ESR)   [ Time Frame: Baseline, Week 12 and Week 24 ]

Measure Type Secondary
Measure Title DAS28 Score Based on Erythrocyte Sedimentation Rate (DAS28-ESR)
Measure Description The DAS28 score is a combined index that has been developed to measure the disease activity in patients with RA and has been extensively validated for its use in clinical studies. The DAS28-ESR assessment involved evaluating the number of tender (TJC) and swollen (SJC) joints (out of 28 specified joints), serum ESR, and patient global assessment of disease activity (VAS from 0 to 100, very well to extremely bad). The individual results are summed using a formula. The DAS28 is a number on a scale from 0 to 10 indicating the current activity of the patient's RA. A higher score indicates higher disease activity.
Time Frame Baseline, Week 12 and Week 24  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Full Analysis Set (FAS) was defined as the set of patients who received at least 1 dose of the randomised treatment and who had at least 1 evaluable primary efficacy measurement after their first dose of randomised treatment. Patients were analysed according to the randomised treatment in the primary analysis.

Reporting Groups
  Description
FKB327 Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks.
Humira® Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks.

Measured Values
   FKB327   Humira® 
Participants Analyzed 
[Units: Participants]
 363   358 
DAS28 Score Based on Erythrocyte Sedimentation Rate (DAS28-ESR) 
[Units: Units on a scale]
Mean (Standard Deviation)
   
Baseline (number analyzed = 361, 355)   6.52  (0.941)   6.56  (0.902) 
Week 12 (number analyzed = 349, 340)   4.24  (1.382)   4.24  (1.353) 
Week 24 (number analyzed = 342, 338)   3.82  (1.384)   3.85  (1.371) 

No statistical analysis provided for DAS28 Score Based on Erythrocyte Sedimentation Rate (DAS28-ESR)



15.  Other Pre-specified:   Percentage of Patients Developing Anti-drug Antibodies (ADAs)   [ Time Frame: Week 24 ]

Measure Type Other Pre-specified
Measure Title Percentage of Patients Developing Anti-drug Antibodies (ADAs)
Measure Description Blood samples for the assessment of ADA activity were collected at Baseline (Week 0), prior to dosing at Weeks 2, 4, 12, and 24.
Time Frame Week 24  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Safety Analysis Set was defined as the set of patients who received at least 1 dose of randomised treatment. The Safety Analysis Set was used for all safety analyses. Patient safety data were analysed according to treatment actually received.

Reporting Groups
  Description
FKB327 Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks.
Humira® Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks.

Measured Values
   FKB327   Humira® 
Participants Analyzed 
[Units: Participants]
 366   362 
Percentage of Patients Developing Anti-drug Antibodies (ADAs) 
[Units: Percentage of patients]
   
Baseline (Positive)   4.4   5.5 
Baseline (Negative)   95.4   94.2 
Baseline (Missing)   0.3   0.3 
Last sampling day (Positive)   61.7   59.1 
Last sampling day (Negative)   38.3   40.9 

No statistical analysis provided for Percentage of Patients Developing Anti-drug Antibodies (ADAs)



16.  Other Pre-specified:   Trough Adalimumab Concentration   [ Time Frame: Week 24 ]

Measure Type Other Pre-specified
Measure Title Trough Adalimumab Concentration
Measure Description Blood samples for the quantification of adalimumab concentration in serum were collected at Baseline (Week 0), prior to dosing at Weeks 2, 4, 12 and 20, and Week 24. Samples were taken prior to dosing (trough samples).
Time Frame Week 24  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Pharmacokinetic Analysis Set (PKAS) was defined as the set of patients who received at least 1 dose of the randomised treatment and had at least 1 serum adalimumab concentration result after receiving randomised treatment.

Reporting Groups
  Description
FKB327 Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks.
Humira® Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks.

Measured Values
   FKB327   Humira® 
Participants Analyzed 
[Units: Participants]
 364   358 
Trough Adalimumab Concentration 
[Units: ng/mL]
Geometric Least Squares Mean (95% Confidence Interval)
   
Week 2   2434.6 
 (2321.4 to 2553.2) 
 2089.1 
 (1990.9 to 2192.2) 
Week 4   3450.6 
 (3223.2 to 3694.1) 
 2932.1 
 (2737 to 3141.1) 
Week 12   4316.3 
 (3919.6 to 4753.2) 
 3851.5 
 (3493.9 to 4245.7) 
Week 20   4369.8 
 (3892.3 to 4905.9) 
 3873 
 (3445.9 to 4353) 
Week 24   4126 
 (3645.1 to 4670.4) 
 3758.2 
 (3316.8 to 4258.3) 

No statistical analysis provided for Trough Adalimumab Concentration




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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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 agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Clinical Trial Information
Organization: Fujifilm Kyowa Kirin Biologics Co., Ltd., EU Branch
phone: +44 1896 668 173
e-mail: Clinical-Trials@fk-b.com



Responsible Party: Fujifilm Kyowa Kirin Biologics Co., Ltd.
ClinicalTrials.gov Identifier: NCT02260791     History of Changes
Other Study ID Numbers: FKB327-002
First Submitted: July 29, 2014
First Posted: October 9, 2014
Results First Submitted: July 5, 2017
Results First Posted: September 20, 2017
Last Update Posted: October 20, 2017