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

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ClinicalTrials.gov Identifier: NCT02260791
Recruitment Status : Completed
First Posted : October 9, 2014
Results First Posted : September 20, 2017
Last Update Posted : November 28, 2017
Sponsor:
Information provided by (Responsible Party):
Fujifilm Kyowa Kirin Biologics Co., Ltd.

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®
Enrollment 728
Recruitment Details 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

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).

Arm/Group Title FKB327 Humira®
Hide Arm/Group Description Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks. Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks.
Period Title: Overall Study
Started 366 362
Completed 333 328
Not Completed 33 34
Reason Not Completed
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
Arm/Group Title FKB327 Humira® Total
Hide Arm/Group Description Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks. Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks. Total of all reporting groups
Overall Number of Baseline Participants 366 362 728
Hide Baseline Analysis Population Description
The Safety Analysis Set was defined as the set of patients who received at least 1 dose of randomised treatment.
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 366 participants 362 participants 728 participants
53
(18 to 85)
53.6
(21 to 93)
53.3
(18 to 93)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 366 participants 362 participants 728 participants
<18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
302
  82.5%
299
  82.6%
601
  82.6%
>65 years
64
  17.5%
63
  17.4%
127
  17.4%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 366 participants 362 participants 728 participants
Female
281
  76.8%
284
  78.5%
565
  77.6%
Male
85
  23.2%
78
  21.5%
163
  22.4%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 366 participants 362 participants 728 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  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 366 participants 362 participants 728 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
1.Primary Outcome
Title American College of Rheumatology (ACR) 20 Response Rate
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title FKB327 Humira®
Hide Arm/Group Description:
Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks.
Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks.
Overall Number of Participants Analyzed 363 358
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
72.5
(67.5 to 77.0)
74.3
(69.4 to 78.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FKB327, Humira®
Comments 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.
Type of Statistical Test Equivalence
Comments -12% to +15% equivalence margin using 90% CI around the difference in ACR20 response rate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.8
Confidence Interval (2-Sided) 90%
-7.3 to 3.6
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Disease Activity Score 28 (DAS28) Based on C-reactive Protein (DAS28-CRP) Score
Hide 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 Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title FKB327 Humira®
Hide Arm/Group Description:
Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks.
Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks.
Overall Number of Participants Analyzed 363 358
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 362 participants 358 participants
6.05  (0.913) 6.06  (0.852)
Week 2 Number Analyzed 361 participants 351 participants
4.92  (1.070) 4.86  (1.203)
Week 4 Number Analyzed 357 participants 348 participants
4.44  (1.317) 4.43  (1.383)
Week 8 Number Analyzed 348 participants 345 participants
4.11  (1.295) 4.09  (1.397)
Week 12 Number Analyzed 351 participants 340 participants
3.81  (1.320) 3.85  (1.339)
Week 16 Number Analyzed 350 participants 341 participants
3.68  (1.304) 3.67  (1.419)
Week 20 Number Analyzed 344 participants 336 participants
3.58  (1.329) 3.57  (1.388)
Week 24 Number Analyzed 340 participants 339 participants
3.47  (1.298) 3.47  (1.336)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FKB327, Humira®
Comments 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.
Type of Statistical Test Equivalence
Comments 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.
Method of Estimation Estimation Parameter Difference in least square mean
Estimated Value 0.01
Confidence Interval (2-Sided) 95%
-0.16 to 0.18
Estimation Comments [Not Specified]
3.Secondary Outcome
Title ACR20 Response Rates Over Time
Hide 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 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title FKB327 Humira®
Hide Arm/Group Description:
Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks.
Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks.
Overall Number of Participants Analyzed 363 358
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of responders
Week 2 Number Analyzed 362 participants 352 participants
37.3
(32.3 to 42.5)
31
(26.2 to 36.1)
Week 4 Number Analyzed 359 participants 349 participants
51
(45.7 to 56.3)
52.4
(47.1 to 57.8)
Week 8 Number Analyzed 353 participants 347 participants
64.6
(59.4 to 69.6)
67.7
(62.5 to 72.6)
Week 12 Number Analyzed 351 participants 342 participants
69.2
(64.1 to 74)
72.2
(67.2 to 76.9)
Week 16 Number Analyzed 350 participants 342 participants
74.6
(69.7 to 79.1)
74.9
(69.9 to 79.4)
Week 20 Number Analyzed 345 participants 338 participants
78
(73.2 to 82.2)
77.8
(73 to 82.1)
Week 24 Number Analyzed 341 participants 338 participants
77.1
(72.3 to 81.5)
79.3
(74.6 to 83.5)
4.Secondary Outcome
Title ACR50 Response Rates Over Time
Hide 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 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title FKB327 Humira®
Hide Arm/Group Description:
Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks.
Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks.
Overall Number of Participants Analyzed 363 358
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of responders
Week 2 Number Analyzed 362 participants 352 participants
5
(3 to 7.7)
8.8
(6.1 to 12.3)
Week 4 Number Analyzed 359 participants 349 participants
17.3
(13.5 to 21.6)
17.8
(13.9 to 22.2)
Week 8 Number Analyzed 353 participants 346 participants
28.9
(24.2 to 33.9)
30.9
(26.1 to 36.1)
Week 12 Number Analyzed 351 participants 342 participants
37.6
(32.5 to 42.9)
35.1
(30 to 40.4)
Week 16 Number Analyzed 350 participants 342 participants
39.4
(34.3 to 44.8)
44.7
(39.4 to 50.2)
Week 20 Number Analyzed 345 participants 339 participants
45.5
(40.2 to 50.9)
46
(40.6 to 51.5)
Week 24 Number Analyzed 341 participants 338 participants
49
(43.6 to 54.4)
49.4
(44 to 54.9)
5.Secondary Outcome
Title ACR70 Response Rates Over Time
Hide 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 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title FKB327 Humira®
Hide Arm/Group Description:
Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks.
Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks.
Overall Number of Participants Analyzed 363 358
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of responders
Week 2 Number Analyzed 362 participants 352 participants
0.3
(0 to 1.5)
2.3
(1 to 4.4)
Week 4 Number Analyzed 359 participants 349 participants
4.5
(2.6 to 7.1)
6.9
(4.5 to 10.1)
Week 8 Number Analyzed 353 participants 347 participants
11.3
(8.2 to 15.1)
10.7
(7.6 to 14.4)
Week 12 Number Analyzed 351 participants 342 participants
15.4
(11.8 to 19.6)
13.2
(9.8 to 17.2)
Week 16 Number Analyzed 350 participants 342 participants
17.4
(13.6 to 21.8)
19
(15 to 23.6)
Week 20 Number Analyzed 345 participants 339 participants
20.9
(16.7 to 25.5)
23.6
(19.2 to 28.5)
Week 24 Number Analyzed 342 participants 338 participants
21.3
(17.1 to 26.1)
25.1
(20.6 to 30.1)
6.Secondary Outcome
Title Swollen Joint Count
Hide 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 Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title FKB327 Humira®
Hide Arm/Group Description:
Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks.
Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks.
Overall Number of Participants Analyzed 363 358
Mean (Standard Deviation)
Unit of Measure: Count / Score
Baseline 16.3  (9.1) 16  (8.96)
Week 24 3.8  (6.04) 3.5  (5.23)
7.Secondary Outcome
Title Tender Joint Count
Hide 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 Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title FKB327 Humira®
Hide Arm/Group Description:
Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks.
Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks.
Overall Number of Participants Analyzed 363 358
Mean (Standard Deviation)
Unit of Measure: Count / Score
Baseline 26.2  (14.49) 25.9  (14.52)
Week 24 8.5  (10.56) 8.1  (9.36)
8.Secondary Outcome
Title Analysis of Serum C-Reactive Protein (CRP) Concentration
Hide 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 Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title FKB327 Humira®
Hide Arm/Group Description:
Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks.
Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks.
Overall Number of Participants Analyzed 363 358
Mean (Standard Deviation)
Unit of Measure: mg/L
Baseline 25.12  (26.746) 26.73  (28.534)
Week 24 10.98  (16.819) 11.78  (18.528)
9.Secondary Outcome
Title Patient Assessment of Disease Activity
Hide 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 Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title FKB327 Humira®
Hide Arm/Group Description:
Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks.
Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks.
Overall Number of Participants Analyzed 363 358
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 68  (17.98) 68.2  (18.18)
Week 24 35.2  (24.04) 33.2  (23.4)
10.Secondary Outcome
Title Physician Assessment of Disease Activity
Hide 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 Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title FKB327 Humira®
Hide Arm/Group Description:
Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks.
Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks.
Overall Number of Participants Analyzed 363 358
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 68.4  (14.58) 66.2  (15.48)
Week 24 21.5  (17.29) 21.5  (16.97)
11.Secondary Outcome
Title Patient's Assessment of Pain
Hide 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 Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title FKB327 Humira®
Hide Arm/Group Description:
Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks.
Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks.
Overall Number of Participants Analyzed 363 358
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 66.8  (18.71) 67.7  (18.56)
Week 24 34.7  (23.86) 33.6  (23.86)
12.Secondary Outcome
Title Health Assessment Questionnaire Disability Index (HAQ-DI)
Hide 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 Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title FKB327 Humira®
Hide Arm/Group Description:
Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks.
Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks.
Overall Number of Participants Analyzed 363 358
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 1.78  (0.544) 1.8  (0.538)
Week 24 1.21  (0.696) 1.26  (0.719)
13.Secondary Outcome
Title DAS28-CRP Score Over Time
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title FKB327 Humira®
Hide Arm/Group Description:
Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks.
Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks.
Overall Number of Participants Analyzed 363 358
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 362 participants 358 participants
6.05  (0.913) 6.06  (0.852)
Week 24 Number Analyzed 340 participants 339 participants
3.47  (1.298) 3.47  (1.336)
14.Secondary Outcome
Title DAS28 Score Based on Erythrocyte Sedimentation Rate (DAS28-ESR)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title FKB327 Humira®
Hide Arm/Group Description:
Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks.
Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks.
Overall Number of Participants Analyzed 363 358
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 361 participants 355 participants
6.52  (0.941) 6.56  (0.902)
Week 12 Number Analyzed 349 participants 340 participants
4.24  (1.382) 4.24  (1.353)
Week 24 Number Analyzed 342 participants 338 participants
3.82  (1.384) 3.85  (1.371)
15.Other Pre-specified Outcome
Title Percentage of Patients Developing Anti-drug Antibodies (ADAs)
Hide 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 Baseline and last sampling day
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Hide Analysis Population Description
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.
Arm/Group Title FKB327 Humira®
Hide Arm/Group Description:
Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks.
Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks.
Overall Number of Participants Analyzed 366 362
Measure Type: Number
Unit of Measure: 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
16.Other Pre-specified Outcome
Title Trough Adalimumab Concentration
Hide 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 2, Week 4, Week 12, Week 20, and Week 24
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Hide Analysis Population Description
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.
Arm/Group Title FKB327 Humira®
Hide Arm/Group Description:
Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks.
Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks.
Overall Number of Participants Analyzed 364 358
Geometric Least Squares Mean (95% Confidence Interval)
Unit of Measure: ng/mL
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)
Time Frame Patients were carefully monitored for adverse events from signing of informed consent until Week 24 (for patients who entered the open-label extension), Week 26 (for patients who did not enter the open-label extension), or the Early Termination visit. In total this covered a period of approximately 1 year and 6 months.
Adverse Event Reporting Description Serious adverse events were followed until resolution, the Investigator confirmed the event was unlikely to resolve or the patient was recorded as lost to follow-up.
 
Arm/Group Title FKB327 Humira®
Hide Arm/Group Description Patients were administered subcutaneous (sc) FKB327 40 mg every other week (eow). The treatment period was 22 weeks. Patients were administered subcutaneous (sc) Humira 40 mg every other week (eow). The treatment period was 22 weeks.
All-Cause Mortality
FKB327 Humira®
Affected / at Risk (%) Affected / at Risk (%)
Total   1/366 (0.27%)      0/362 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
FKB327 Humira®
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   15/366 (4.10%)      19/362 (5.25%)    
Gastrointestinal disorders     
Anal fistula * 1  1/366 (0.27%)  1 0/362 (0.00%)  0
Hepatobiliary disorders     
Cholelithiasis * 1  0/366 (0.00%)  0 1/362 (0.28%)  1
Immune system disorders     
Amyloidosis * 1  1/366 (0.27%)  1 0/362 (0.00%)  0
Infections and infestations     
Pneumonia * 1  3/366 (0.82%)  3 0/362 (0.00%)  0
Disseminated tuberculosis * 1  1/366 (0.27%)  1 1/362 (0.28%)  1
Pulmonary tuberculosis * 1  0/366 (0.00%)  0 2/362 (0.55%)  2
Bronchopneumonia * 1  1/366 (0.27%)  1 0/362 (0.00%)  0
Cervicitis * 1  1/366 (0.27%)  1 0/362 (0.00%)  0
Erysipelas * 1  1/366 (0.27%)  1 0/362 (0.00%)  0
Gangrene * 1  1/366 (0.27%)  1 0/362 (0.00%)  0
Latent tuberculosis * 1  1/366 (0.27%)  1 0/362 (0.00%)  0
Osteomyelitis chronic * 1  0/366 (0.00%)  0 1/362 (0.28%)  1
Pyelonephritis acute * 1  0/366 (0.00%)  0 1/362 (0.28%)  1
Sepsis * 1  1/366 (0.27%)  1 0/362 (0.00%)  0
Urinary tract infection * 1  1/366 (0.27%)  1 0/362 (0.00%)  0
Injury, poisoning and procedural complications     
Hip fracture * 1  0/366 (0.00%)  0 2/362 (0.55%)  2
Femoral neck fracture * 1  0/366 (0.00%)  0 1/362 (0.28%)  1
Spinal compression fracture * 1  0/366 (0.00%)  0 1/362 (0.28%)  1
Traumatic fracture * 1  0/366 (0.00%)  0 1/362 (0.28%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Squamous cell carcinoma * 1  1/366 (0.27%)  1 1/362 (0.28%)  1
Lymphoma * 1  0/366 (0.00%)  0 1/362 (0.28%)  1
Plasma cell myeloma * 1  1/366 (0.27%)  1 0/362 (0.00%)  0
Uterine leiomyoma * 1  0/366 (0.00%)  0 1/362 (0.28%)  1
Nervous system disorders     
Cerebrovascular accident * 1  1/366 (0.27%)  1 1/362 (0.28%)  1
Renal and urinary disorders     
Nephrotic syndrome * 1  1/366 (0.27%)  1 0/362 (0.00%)  0
Renal colic * 1  0/366 (0.00%)  0 1/362 (0.28%)  1
Respiratory, thoracic and mediastinal disorders     
Lung infiltration * 1  0/366 (0.00%)  0 1/362 (0.28%)  1
Skin and subcutaneous tissue disorders     
Lichen sclerosus * 1  1/366 (0.27%)  1 0/362 (0.00%)  0
Vascular disorders     
Aortic aneurysm * 1  0/366 (0.00%)  0 1/362 (0.28%)  1
Thrombophlebitis * 1  1/366 (0.27%)  1 0/362 (0.00%)  0
Thrombosis * 1  0/366 (0.00%)  0 1/362 (0.28%)  1
1
Term from vocabulary, MedDRA (17.1)
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
FKB327 Humira®
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   26/366 (7.10%)      29/362 (8.01%)    
Infections and infestations     
Nasopharyngitis * 1  26/366 (7.10%)  26 29/362 (8.01%)  29
1
Term from vocabulary, MedDRA (17.1)
*
Indicates events were collected by non-systematic assessment
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.
Investigator and Sponsor will discuss the preparation of a manuscript for publication in a peer reviewed journal or an abstract for presentation. Either party may undertake the task but both must agree to the strategy before work is started. Each party will allow the other 30 days to comment before any results are submitted for publication or presentation. Authorship should reflect work done by the Investigators and Sponsor, in accordance with recognised principles of scientific collaboration.
Results Point of Contact
Name/Title: Clinical Trial Information
Organization: Fujifilm Kyowa Kirin Biologics Co., Ltd., EU Branch
Phone: +44 1896 668 173
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: November 28, 2017