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A Study to Compare FKB327 Long-term Safety, Efficacy and Immunogenicity With Humira® in Rheumatoid Arthritis Patients (ARABESC-OLE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02405780
Recruitment Status : Completed
First Posted : April 1, 2015
Results First Posted : March 26, 2019
Last Update Posted : March 26, 2019
Sponsor:
Information provided by (Responsible Party):
Fujifilm Kyowa Kirin Biologics Co., Ltd.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Arthritis, Rheumatoid
Interventions Drug: FKB327
Drug: Humira®
Enrollment 645
Recruitment Details  
Pre-assignment Details  
Arm/Group Title FKB327-FKB327-FKB327 FKB327-Humira-FKB327 Humira-FKB327-FKB327 Humira-Humira-FKB327
Hide Arm/Group Description

Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to FKB327 in Period I of study FKB327-003 (F-F).

Period II: From week 30 all subjects received FKB327; (F-F-F).

Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study FKB327-002 and were re-randomized to the reference product, Humira, during Period I of study FKB327-003 (F-H).

Period II: From week 30 all subjects received FKB327; (F-H-F).

Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to FKB327 during Period I of study FKB327-003 (H-F).

Period II: From week 30 all subjects received FKB327; (H-F-F).

Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002, and were re-randomized to the reference product Humira during Period I of study FKB327-003 (H-H).

Period II: From week 30 all subjects received FKB327; (H-H-F).

Period Title: Period I
Started 216 108 108 213
Completed 189 100 93 190
Not Completed 27 8 15 23
Reason Not Completed
Adverse Event             8             0             3             7
Medical reasons             1             1             0             1
Screening Failure             1             0             1             0
Withdrawal by Subject             9             1             3             4
Non-compliance with study procedures             8             6             8             11
Period Title: Period II
Started 189 100 93 190
Completed 174 88 81 172
Not Completed 15 12 12 18
Reason Not Completed
Adverse Event             3             5             4             11
Medical reason             0             1             0             0
Pregnancy             0             0             1             0
Withdrawal by Subject             7             4             0             3
Non-compliance with study procedures             5             2             7             4
Arm/Group Title FKB327-FKB327 FKB327-Humira Humira-FKB327 Humira-Humira Total
Hide Arm/Group Description This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to receive FKB327 in Study FKB327-003. This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to receive the reference product Humira in Study FKB327-003. This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to receive FKB327 in Study FKB327-003. This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to receive the reference product Humira in Study FKB327-003. Total of all reporting groups
Overall Number of Baseline Participants 216 108 108 213 645
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 216 participants 108 participants 108 participants 213 participants 645 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
183
  84.7%
92
  85.2%
96
  88.9%
169
  79.3%
540
  83.7%
>=65 years
33
  15.3%
16
  14.8%
12
  11.1%
44
  20.7%
105
  16.3%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 216 participants 108 participants 108 participants 213 participants 645 participants
Female
162
  75.0%
85
  78.7%
83
  76.9%
171
  80.3%
501
  77.7%
Male
54
  25.0%
23
  21.3%
25
  23.1%
42
  19.7%
144
  22.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 216 participants 108 participants 108 participants 213 participants 645 participants
American Indian or Alaska Native
1
   0.5%
0
   0.0%
0
   0.0%
1
   0.5%
2
   0.3%
Asian
1
   0.5%
0
   0.0%
1
   0.9%
0
   0.0%
2
   0.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   0.5%
1
   0.9%
2
   1.9%
2
   0.9%
6
   0.9%
White
187
  86.6%
90
  83.3%
90
  83.3%
185
  86.9%
552
  85.6%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
26
  12.0%
17
  15.7%
15
  13.9%
25
  11.7%
83
  12.9%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 216 participants 108 participants 108 participants 213 participants 645 participants
Canada
1
   0.5%
1
   0.9%
1
   0.9%
2
   0.9%
5
   0.8%
Chile
13
   6.0%
7
   6.5%
6
   5.6%
14
   6.6%
40
   6.2%
Czechia
22
  10.2%
9
   8.3%
11
  10.2%
22
  10.3%
64
   9.9%
Germany
7
   3.2%
4
   3.7%
3
   2.8%
8
   3.8%
22
   3.4%
Peru
26
  12.0%
17
  15.7%
15
  13.9%
26
  12.2%
84
  13.0%
Poland
41
  19.0%
22
  20.4%
22
  20.4%
39
  18.3%
124
  19.2%
Romania
8
   3.7%
4
   3.7%
3
   2.8%
8
   3.8%
23
   3.6%
Russia
33
  15.3%
18
  16.7%
16
  14.8%
29
  13.6%
96
  14.9%
Spain
2
   0.9%
1
   0.9%
2
   1.9%
4
   1.9%
9
   1.4%
Ukraine
39
  18.1%
14
  13.0%
17
  15.7%
37
  17.4%
107
  16.6%
United States
24
  11.1%
11
  10.2%
12
  11.1%
24
  11.3%
71
  11.0%
1.Primary Outcome
Title Number of Patients With Adverse Events as a Measure of Safety Per Treatment Group in Period I
Hide Description

Period I: Patients were carefully monitor for Adverse Events from signing of informed consent until week 30 and thereafter during Period II of the study. For patients who discontinued early, a follow-up period of 4 weeks was added to the Early Termination Visit.

The investigator actively asked the patients for Adverse Events. Patients spontaneously reported Adverse Events to the Investigator during clinic visits or in between visits.

Time Frame Period I: from Week 0 up until Week 30;
Hide Outcome Measure Data
Hide Analysis Population Description
Each patient was counted once within each System Organ Class (SOC) and Preferred Term (PT). A patient may have had multiple events counted. Treatment Emergen Adverse Events (TEAE) defined as AEs that started or increased in severity after the first study dose and counted under the treatment arm.
Arm/Group Title FKB327-FKB327 FKB327-Humira Humira-FKB327 Humira-Humira
Hide Arm/Group Description:
Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to FKB327 in Period I of study FKB327-003 (F-F).
Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study FKB327-002 and were re-randomized to the reference product, Humira, during Period I of study FKB327-003 (F-H).
Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to FKB327 during Period I of study FKB327-003 (H-F).
Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002, and were re-randomized to the reference product Humira during Period I of study FKB327-003 (H-H).
Overall Number of Participants Analyzed 216 108 108 213
Measure Type: Number
Unit of Measure: participants
Death 0 0 1 1
Treatment Emergent Deaths 0 0 1 1
At least 1 TEAE 103 59 59 117
At least 1 severe TEAE 5 2 3 2
At least 1 treatment related TEAE 39 21 27 49
Premature Discontinuation due to a TEAE 10 0 4 11
Treatment Interruption due to a TEAE 19 9 14 20
2.Primary Outcome
Title Number of Patients With Adverse Events as a Measure of Safety in Period II - Single Treatment Period
Hide Description From week 30 all subjects were transferred to receive FKB327 treatment. Adverse Events were contentiously monitored and recorded during Period II. For patients discontinuing the study prematurely, a follow-up period of 4 weeks was added to the Early Termination Visit. The data for Period II is based on the number of patients in the Safety Analysis Set that entered Period II.
Time Frame Period II: from Week 30 up to Week 80
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title FKB327
Hide Arm/Group Description:

Period II: From week 30 all patients received one subcutaneous injection every other week of 40 mg/0.8 mL presented in an auto-injector (AI) or in a pre-filled syringe (PFS).

Based on the design of the study and to what treatment groups the subjects were randomised to in Period I, some patients received continuous treatment with FKB327 40 mg/0.8mL every other week by subcutaneous injection for up to 76 weeks. This was applicable to subjects in treatment groups (F-F-F) and (H-F-F)

Overall Number of Participants Analyzed 572
Measure Type: Count of Participants
Unit of Measure: Participants
Death
2
   0.3%
Treatment Emergent Deaths
2
   0.3%
At least 1 TEAE
340
  59.4%
At least 1 severe TEAE
19
   3.3%
At least 1 treatment related TEAE
126
  22.0%
Premature Discontinuation due to a TEAE
25
   4.4%
Treatment Interruption due to a TEAE
36
   6.3%
3.Primary Outcome
Title Number of Patients With Serious Adverse Events as a Measure of Safety Per Treatment Group in Period I
Hide Description

A Serious Adverse Event (SAE) was defined in the Protocol as: Death; or a Life-threatening Adverse Event (AE); Inpatient Hospitalization; Persistant or significant disability or incapacity; A congenital anomaly/birth defect; An important medical event that may not have resulted in death, have been life-threatening, or required hospitalization, but may have jeopardized the patient and may have required medical intervention to prevent 1 of the outcomes listed in this definition.

SAEs were followed until resolution, the investigator confirmed the event was unlikely to resolve or the patient was recorded as lost to follow-up.

Time Frame Period I: from Week 0 up until Week 30
Hide Outcome Measure Data
Hide Analysis Population Description
Each patient was counted once within each System Organ Class (SOC) and Preferred Term (PT). Death defined as a fatal outcome of a (S) AE.
Arm/Group Title FKB327-FKB327 FKB327-Humira Humira-FKB327 Humira-Humira
Hide Arm/Group Description:
Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to FKB327 in Period I of study FKB327-003 (F-F).
Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study FKB327-002 and were re-randomized to the reference product, Humira, during Period I of study FKB327-003 (F-H).
Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to FKB327 during Period I of study FKB327-003 (H-F).
Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002, and were re-randomized to the reference product Humira during Period I of study FKB327-003 (H-H).
Overall Number of Participants Analyzed 216 108 108 213
Measure Type: Number
Unit of Measure: participants
Deaths 0 0 1 1
Treatment Emergent Deaths 0 0 1 1
Treatment Discontinuation due to a TESAE 0 0 0 2
Treatment Interruption due to a TESAE 3 2 4 2
At least 1 TESAE 5 7 5 7
Number of TESAE 7 9 9 7
At least 1 SAE 5 7 5 7
4.Primary Outcome
Title Number of Patients With Serious Adverse Events as a Measure of Safety in Period II - Single Treatment Period
Hide Description

Period II: at week 30 all patients were transferred to receive FKB327.

Each subject was counted once within each System Organ Class (SOC) and Preferred Term (PT). Death defined as a fatal outcome of a (S)AE.

SAEs were followed until resolution, the investigator confirmed the event was unlikely to resolve or the patient was lost to follow-up.

Time Frame Period II: from Week 30 up to Week 80
Hide Outcome Measure Data
Hide Analysis Population Description
Each patient was counted once within each System Organ Class (SOC) and Preferred Term (PT). Death defined as a fatal outcome of a (S) AE.
Arm/Group Title FKB327
Hide Arm/Group Description:

Period II: From week 30 all subjects received one subcutaneous injection every other week of FKB327 40 mg/0.8 mL presented in an auto-injector (AI) or in a pre-filled syringe (PFS) .

Based on the design of the study and to what treatment groups the subjects were randomised to in Period I, some patients received continuous treatment with FKB327 40 mg/0.8mL every other week by subcutaneous injection for up to 76 weeks. This was applicable to subjects in treatment groups (F-F-F) and (H-F-F)

Overall Number of Participants Analyzed 572
Measure Type: Count of Participants
Unit of Measure: Participants
Death
2
   0.3%
Treatment Emergent Deaths
2
   0.3%
At least 1 severe TEAE
19
   3.3%
Treatment Discontinuation due to a TESEA
10
   1.7%
Treatment Interruption due to a TESAE
6
   1.0%
At least 1 TESAE
33
   5.8%
Number of TESAE
45
   7.9%
At least 1 SAE
33
   5.8%
5.Primary Outcome
Title Changes in Vital Signs as a Measure of Safety - Systolic Blood Pressure
Hide Description

Systolic Blood Pressure is part of Vital Signs which were part of the subject safety evaluations. Systolic Blood Pressure was measured at the following time-points: Week 0, Week 4, Week 8, Week 12, Week 24 and Week 80/End o Study (EOS). Systolic Blood Pressure with changes from Baseline_002 (NCT022600791) was summarized by treatment sequence over the whole study period for each visit.

Baseline_002 is defined as the last non-missing measurement collected prior to the first study medication administered at Week 0 from Study FKB327-002.

Time Frame From Week 0 to Week 80
Hide Outcome Measure Data
Hide Analysis Population Description
The number of patients in the Safety Analysis Set; is equal to the number of patients who entered Period I. The number of patients at the following visit is the number of patients who at a given timepoint had a measurement completed for the Safety Analysis Set.
Arm/Group Title FKB327-FKB327-FKB327 FKB327-Humira-FKB327 Humira-FKB327-FKB327 Humira-Humira-FKB327
Hide Arm/Group Description:

Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to receive FKB327 in Study FKB327-003 (F-F).

Period II: From week 30 all subjects received FKB327 (F-F-F).

Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to receive the reference product Humira in Study FKB327-003 (F-H).

Period II: From week 30 all subjects received FKB327 (F-H-F).

Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to receive FKB327 in Study FKB327-003 (H-F).

Period II: From week 30 all subjects received FKB327 (H-F-F).

Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to receive the reference product Humira in Study FKB327-003 (H-H).

Period II: From week 30 all subjects received FKB327 (H-H-F).

Overall Number of Participants Analyzed 216 108 108 213
Median (Full Range)
Unit of Measure: mmHg
Baseline_002 Number Analyzed 216 participants 108 participants 108 participants 213 participants
125.0
(86 to 168)
125.5
(94 to 174)
131.0
(88 to 167)
129.0
(90 to 162)
Week 0 Number Analyzed 216 participants 108 participants 108 participants 213 participants
125.0
(84 to 166)
123.5
(90 to 160)
127.0
(98 to 179)
125.0
(90 to 163)
Changes from Baseline_002 at week 0 Number Analyzed 216 participants 108 participants 108 participants 213 participants
0.0
(-34 to 35)
-2.0
(-30 to 32)
-2.0
(-44 to 32)
-2.0
(-50 to 51)
Week 4 Number Analyzed 213 participants 106 participants 107 participants 208 participants
124.0
(82 to 172)
125.0
(95 to 164)
124.0
(92 to 186)
125
(94 to 167)
Changes from Baseline_002 at week 4 Number Analyzed 213 participants 106 participants 107 participants 208 participants
0.0
(-56 to 38)
0.0
(-22 to 44)
-6.0
(-39 to 39)
-1.0
(-37 to 36)
Week 8 Number Analyzed 205 participants 104 participants 104 participants 204 participants
124.0
(88 to 154)
124.0
(89 to 153)
128.0
(92 to 160)
125.0
(92 to 156)
Changes from Baseline_002 at week 8 Number Analyzed 205 participants 104 participants 104 participants 204 participants
-2.0
(-47 to 32)
-0.5
(-28 to 41)
-1.5
(-35 to 30)
-2.0
(-38 to 36)
Week 12 Number Analyzed 204 participants 104 participants 103 participants 204 participants
125.0
(91 to 159)
124.5
(86 to 165)
126.0
(89 to 167)
125.0
(92 to 170)
Changes from Baseline_002 at week 12 Number Analyzed 204 participants 104 participants 103 participants 204 participants
0.0
(-35 to 45)
-2.0
(-40 to 35)
-2.0
(-44 to 28)
0.0
(-46 to 40)
Week 24 Number Analyzed 198 participants 102 participants 97 participants 200 participants
125.0
(90 to 155)
127.5
(92 to 156)
125.0
(86 to 163)
126.0
(94 to 176)
Changes from Baseline_002 at week 24 Number Analyzed 198 participants 102 participants 97 participants 200 participants
-2.0
(-46 to 36)
0.0
(-38 to 33)
-5.0
(-44 to 28)
0.0
(-49 to 37)
Week 80/EOS Number Analyzed 174 participants 88 participants 81 participants 172 participants
126.0
(90 to 157)
125.0
(88 to 171)
126.0
(91 to 163)
125.0
(98 to 163)
Changes from Baseline_002 at week 80/EOS Number Analyzed 174 participants 88 participants 81 participants 172 participants
-0.5
(-53 to 53)
0.0
(-37 to 41)
-2.0
(-47 to 27)
-1.5
(-42 to 26)
6.Primary Outcome
Title Changes in Vital Signs as a Measure of Safety - Diastolic Blood Pressure
Hide Description

Diastolic Blood Pressure is part of Vital Signs which were part of the subject safety evaluations. Diastolic Blood Pressure was measured at the following time-points: Week 0, Week 4, Week 8, Week 12, Week 24 and Week 80/End o Study (EOS). Diastolic Blood Pressure with changes from Baseline_002 (NCT022600791) was summarized by treatment sequence over the whole study period for each visit measured.

Baseline_002 is defined as the last non-missing measurement collected prior to the first study medication administered at Week 0 from Study FKB327-002.

Time Frame From Week 0 to Week 80
Hide Outcome Measure Data
Hide Analysis Population Description
The number of patients in the Safety Analysis Set; is equal to the number of patients who entered Period I. The number of patients at the following visit is the number of patients who at a given timepoint had a measurement completed for the Safety Analysis Set.
Arm/Group Title FKB327-FKB327-FKB327 FKB327-Humira-FKB327 Humira-FKB327-FKB327 Humira-Humira-FKB327
Hide Arm/Group Description:

Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to receive FKB327 in Study FKB327-003 (F-F).

Period II: From week 30 all subjects received FKB327 (F-F-F).

Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to receive the reference product Humira in Study FKB327-003 (F-H).

Period II: From week 30 all subjects received FKB327 (F-H-F).

Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to receive FKB327 in Study FKB327-003 (H-F).

Period II: From week 30 all subjects received FKB327 (H-F-F).

Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to receive the reference product Humira in Study FKB327-003 (H-H).

Period II: From week 30 all subjects received FKB327 (H-H-F).

Overall Number of Participants Analyzed 216 108 108 213
Median (Full Range)
Unit of Measure: mmHg
Baseline_002 Number Analyzed 216 participants 108 participants 108 participants 213 participants
78.0
(48 to 99)
78.0
(56 to 98)
80.0
(54 to 96)
77.0
(55 to 105)
Week 0 Number Analyzed 216 participants 108 participants 108 participants 213 participants
78.0
(49 to 94)
75.0
(53 to 102)
77.0
(57 to 108)
76.0
(50 to 99)
Changes from Baseline_002 at week 0 Number Analyzed 216 participants 108 participants 108 participants 213 participants
0.0
(-23 to 28)
-1.5
(-25 to 22)
-1.0
(-25 to 24)
0.0
(-31 to 23)
Week 4 Number Analyzed 213 participants 106 participants 107 participants 208 participants
76.0
(51 to 94)
77.0
(59 to 96)
76.0
(58 to 107)
78.0
(55 to 100)
Changes from Baseline_002 at week 4 Number Analyzed 213 participants 106 participants 107 participants 208 participants
0.0
(-33 to 28)
0.0
(-18 to 36)
0.0
(-22 to 25)
0.0
(-27 to 30)
Week 8 Number Analyzed 205 participants 104 participants 104 participants 204 participants
78.0
(59 to 97)
78.0
(58 to 99)
80.0
(57 to 97)
77.0
(51 to 95)
Changes from Baseline_002 at week 8 Number Analyzed 205 participants 104 participants 104 participants 204 participants
0.0
(-26 to 26)
0.0
(-23 to 34)
0.0
(-18 to 15)
0.0
(-30 to 21)
Week 12 Number Analyzed 204 participants 104 participants 103 participants 204 participants
78.0
(52 to 98)
78.5
(56 to 104)
80.0
(58 to 103)
78.0
(58 to 95)
Changes from Baseline_002 at week 12 Number Analyzed 204 participants 104 participants 103 participants 204 participants
0.0
(-26 to 23)
0.0
(-24 to 21)
0.0
(-15 to 31)
0.0
(-26 to 20)
Week 24 Number Analyzed 198 participants 102 participants 97 participants 200 participants
78.0
(52 to 96)
78.0
(52 to 99)
78.0
(50 to 104)
78.0
(55 to 96)
Changes from Baseline_002 at week 24 Number Analyzed 198 participants 102 participants 97 participants 200 participants
1.0
(-22 to 25)
0.0
(-24 to 19)
0.0
(-22 to 16)
0.0
(-36 to 18)
Week 80/EOS Number Analyzed 174 participants 88 participants 81 participants 172 participants
78.0
(41 to 98)
79.0
(60 to 100)
80.0
(56 to 102)
77.0
(50 to 95)
Changes from Baseline_002 at week 80/EOS Number Analyzed 174 participants 88 participants 81 participants 172 participants
0.0
(-42 to 30)
0.0
(-32 to 24)
0.0
(-25 to 18)
0.0
(-48 to 20)
7.Primary Outcome
Title Changes in Vital Signs as a Measure of Safety - Pulse Rate
Hide Description

Pulse rate is part of Vital Signs which were part of the subject safety evaluations. Pulse rate was measured at the following time-points: Weeks 0, 4, 8, 12, 24 and 80/End of Study (EOS). Pulse Rate with changes from Baseline_002 (NCT022600791) was summarized by treatment sequence over the whole study period for each visit.

Baseline_002 is defined as the last non-missing measurement collected prior to the first study medication administered at Week 0 from Study FKB327-002.

Time Frame From Week 0 to Week 80
Hide Outcome Measure Data
Hide Analysis Population Description
The number of patients in the Safety Analysis Set; is equal to the number of patients who entered Period I. The number of patients at the following visits is the number of patients who at a given time point had a measurement completed for the Safety Analysis Set.
Arm/Group Title FKB327-FKB327-FKB327 FKB327-Humira-FKB327 Humira-FKB327-FKB327 Humira-Humira-FKB327
Hide Arm/Group Description:

Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to receive FKB327 in Study FKB327-003 (F-F).

Period II: From week 30 all subjects received FKB327 (F-F-F).

Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to receive the reference product Humira in Study FKB327-003 (F-H).

Period II: From week 30 all subjects received FKB327 (F-H-F).

Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to receive FKB327 in Study FKB327-003 (H-F).

Period II: From week 30 all subjects received FKB327 (H-F-F).

Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to receive the reference product Humira in Study FKB327-003 (H-H).

Period II: From week 30 all subjects received FKB327 (H-H-F).

Overall Number of Participants Analyzed 216 108 108 213
Median (Full Range)
Unit of Measure: Beats per minute (bpm)
Baseline_002 Number Analyzed 216 participants 108 participants 108 participants 213 participants
74.0
(51 to 100)
74.0
(54 to 97)
74.0
(54 to 102)
74.0
(53 to 106)
Week 0 Number Analyzed 216 participants 108 participants 108 participants 213 participants
72.0
(50 to 102)
71.0
(48 to 94)
72.0
(53 to 110)
72.0
(42 to 99)
Changes from Baseline_002 at week 0 Number Analyzed 216 participants 108 participants 108 participants 213 participants
-0.5
(-32 to 28)
-3.0
(-28 to 24)
-3.0
(-23 to 44)
-2.0
(-36 to 29)
Week 4 Number Analyzed 213 participants 106 participants 107 participants 208 participants
72.0
(47 to 112)
72.0
(52 to 94)
74.0
(51 to 105)
72.0
(50 to 102)
Changes from Baseline_002 at week 4 Number Analyzed 213 participants 106 participants 107 participants 208 participants
-2.0
(-29 to 24)
-2.0
(-28 to 24)
-2.0
(-24 to 30)
-1.0
(-37 to 32)
Week 8 Number Analyzed 205 participants 104 participants 104 participants 204 participants
72.0
(53 to 99)
72.0
(54 to 102)
72.0
(53 to 100)
72
(46 to 99)
Changes from Baseline_002 at week 8 Number Analyzed 205 participants 104 participants 104 participants 204 participants
0.0
(-41 to 26)
-2.0
(-26 to 32)
-2.0
(-28 to 19)
-2.0
(-37 to 25)
Week 12 Number Analyzed 204 participants 104 participants 103 participants 204 participants
71.0
(50 to 98)
72.0
(56 to 100)
72.0
(57 to 97)
71.0
(52 to 92)
Changes from Baseline_002 at week 12 Number Analyzed 204 participants 104 participants 103 participants 204 participants
-2.0
(-36 to 30)
-1.5
(-31 to 18)
-1.0
(-28 to 25)
-2.0
(-30 to 19)
Week 24 Number Analyzed 198 participants 102 participants 97 participants 200 participants
73.0
(50 to 103)
72.0
(55 to 96)
72.0
(58 to 99)
72.0
(49 to 95)
Changes from Baseline_002 at week 24 Number Analyzed 198 participants 102 participants 97 participants 200 participants
0.0
(-35 to 26)
-2.0
(-33 to 20)
-2.0
(-29 to 26)
-2.0
(-32 to 34)
Week 80/EOS Number Analyzed 174 participants 88 participants 81 participants 172 participants
74.0
(52 to 110)
72.0
(55 to 94)
72.0
(50 to 96)
73.5
(45 to 111)
Changes from Baseline_002 at week 80/EOS Number Analyzed 174 participants 88 participants 81 participants 172 participants
-1.0
(-31 to 32)
-2.0
(-30 to 19)
-1.0
(-25 to 26)
-1.0
(-37 to 31)
8.Primary Outcome
Title Changes in Vital Signs as a Measure of Safety - Temperature Measurements
Hide Description

Temperature measurements forms part of the vital signs which was one of the continuous safety measurements for the study primary endpoint.

Temperature was measured at week 0, week 4, week 8, week 12, week 24 and at week 80 or at End of Study (EOS).

Temperature with change from Baseline_002 were summarized by treatment sequence over the whole study period.

Baseline_002 is defined as the last non-missing measurement collected prior to the first study medication administration at Week 0 from Study FKB327-002 (NCT02260791).

Time Frame From Week 0 to Week 80
Hide Outcome Measure Data
Hide Analysis Population Description
The number of patients in the Safety Analysis Set; is equal to the number of patients who entered Period I. The number of patients at the following visits is the number of patients who at a given timepoint had a measurement completed for the Safety Analysis Set.
Arm/Group Title FKB327-FKB327-FKB327 FKB327-Humira-FKB327 Humira-FKB327-FKB327 Humira-Humira-FKB327
Hide Arm/Group Description:

Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to receive FKB327 in Study FKB327-003 (F-F).

Period II: From week 30 all subjects received FKB327 (F-F-F).

Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to receive the reference product Humira in Study FKB327-003 (F-H).

Period II: From week 30 all subjects received FKB327 (F-H-F).

Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to receive FKB327 in Study FKB327-003 (H-F).

Period II: From week 30 all subjects received FKB327 (H-F-F).

Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to receive the reference product Humira in Study FKB327-003 (H-H).

Period II: From week 30 all subjects received FKB327 (H-H-F).

Overall Number of Participants Analyzed 216 108 108 213
Median (Full Range)
Unit of Measure: Centigrades
Baseline_002 Number Analyzed 216 participants 108 participants 108 participants 213 participants
36.600
(35.61 to 37.20)
36.600
(35.50 to 37.00)
36.600
(35.60 to 37.30)
36.500
(35.60 to 37.60)
Week 0 Number Analyzed 216 participants 108 participants 108 participants 213 participants
36.500
(35.70 to 37.20)
36.500
(35.50 to 37.10)
36.600
(35.56 to 37.20)
36.500
(35.70 to 37.10)
Changes from Baseline_002 at week 0 Number Analyzed 216 participants 108 participants 108 participants 213 participants
0.000
(-0.80 to 1.19)
0.000
(-1.20 to 0.70)
0.000
(-0.70 to 1.00)
0.000
(-1.00 to 0.80)
Week 4 Number Analyzed 213 participants 106 participants 107 participants 208 participants
36.500
(34.56 to 37.70)
36.500
(35.70 to 37.00)
36.500
(35.20 to 37.11)
36.500
(35.60 to 37.20)
Changes from Baseline_002 at week 4 Number Analyzed 213 participants 106 participants 107 participants 208 participants
0.000
(-1.94 to 1.40)
0.000
(-0.70 to 1.20)
-0.100
(-1.20 to 1.00)
0.000
(-1.20 to 1.00)
Week 8 Number Analyzed 205 participants 104 participants 104 participants 204 participants
36.500
(35.00 to 37.28)
36.500
(35.40 to 37.20)
36.500
(35.60 to 37.20)
36.500
(35.50 to 37.30)
Changes from Baseline_002 at week 8 Number Analyzed 205 participants 104 participants 104 participants 204 participants
0.000
(-1.50 to 1.19)
-0.100
(-0.83 to 1.10)
-0.025
(-0.70 to 0.80)
0.000
(-1.40 to 1.20)
Week 12 Number Analyzed 204 participants 104 participants 103 participants 204 participants
36.500
(35.56 to 37.20)
36.500
(35.10 to 37.10)
36.500
(35.40 to 37.00)
36.500
(35.60 to 37.40)
Changes from Baseline_002 at week 12 Number Analyzed 204 participants 104 participants 103 participants 204 participants
0.000
(-0.94 to 0.80)
0.000
(-1.10 to 0.80)
-0.100
(-1.10 to 0.90)
0.000
(-1.60 to 1.30)
Week 24 Number Analyzed 198 participants 102 participants 97 participants 200 participants
36.500
(35.50 to 37.20)
36.500
(35.50 to 37.90)
36.500
(35.60 to 37.40)
36.500
(35.60 to 37.20)
Changes from Baseline_002 at week 24 Number Analyzed 198 participants 102 participants 97 participants 200 participants
0.000
(-1.00 to 1.00)
0.000
(-0.90 to 1.40)
0.000
(-0.90 to 1.00)
0.000
(-1.10 to 0.80)
Week 80/EOS Number Analyzed 174 participants 88 participants 81 participants 172 participants
36.500
(35.60 to 37.30)
36.500
(35.70 to 37.10)
36.500
(35.30 to 37.00)
36.500
(35.50 to 37.30)
Changes from Baseline_002 at week 80/EOS Number Analyzed 174 participants 88 participants 81 participants 172 participants
0.000
(-1.10 to 1.19)
0.000
(-0.80 to 0.90)
-0.100
(-1.00 to 0.70)
0.000
(-1.00 to 0.90)
9.Primary Outcome
Title Summary of Most Common Clinical Significant Laboratory Parameters Reported as Adverse Events (Reported by ≥1% of the Patients)
Hide Description Clinical Laboratory tests for hematology and serum chemistry were performed by the sites and analysed at a Central Laboratory. Urine dip-stick tests were performed by the sites. Laboratory samples were taken at the following time-points (weeks): 0; 4; 8; 12; 24; 30; 42; 54; 66; 76 and 80/End of Study (EOS). Each result outside its normal range was review and assessed by the investigator whether or not it was Clinically Significant (CS) or Not Clinically Significant (NCS) CS laboratory abnormalities were recorded as AEs.
Time Frame From Week 0 to Week 80
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title FKB327-FKB327 FKB327-Humira Humira-FKB327 Humira-Humira FKB327 Period II
Hide Arm/Group Description:
Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to receive FKB327 in Study FKB327-003 (F-F).
Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to receive the reference product Humira in Study FKB327-003 (F-H).
Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to receive FKB327 in Study FKB327-003 (H-F).
Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to receive the reference product Humira in Study FKB327-003 (H-H).
From Week 30 all patients were treated with FKB327
Overall Number of Participants Analyzed 216 108 108 213 572
Measure Type: Number
Unit of Measure: participants
Anaemia 3 1 2 3 11
Leukopenia 3 1 0 0 2
Neutropenia 3 0 0 1 2
ALT increased 3 2 0 1 10
AST increased 3 0 0 1 7
Dyslipidaemia 1 0 1 1 8
Hypercholesterolaemia 3 3 2 3 2
CRP increased 0 0 0 1 8
Latent TB 3 0 4 4 10
Mycobacterium tuberculosis complex test positive 7 2 2 6 5
Haematuria 1 0 2 2 2
10.Secondary Outcome
Title Changes in Disease Activity Score 28 Based on C Reactive Protein (DAS28 CRP) Score Compared to Baseline as a Measure of Efficacy
Hide Description

The DAS28 score is a combined index that has been developed to measure the disease activity in patients with Rheumatoid arthritis (RA) and has been extensively validated for the use in clinical studies. The DAS28-CRP assessment involved evaluating the number of tender (TJC) and the swollen (SJC) joints (out of 28 specified joints), serum CRP, and patient global assessment of disease activity (Visual analogue scale (VAS) from 0-100, very well to extremely bad). The individual results are summarized using a formula. 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.

During the FKB327-003 study for Period I and Period II the DAS28-CRP score was compared to Baseline in study FKB327-002 (NCT02260791).

Time Frame From Week 0 of FKB327-002 to Week 80
Hide Outcome Measure Data
Hide Analysis Population Description
DAS28-CRP and change from Baseline in Study FKB327-002 (i.e. Baseline_002) in DAS28-CRP were summarized by overall treatment sequence and visit as well as by treatment for each period (Period I and Period II)
Arm/Group Title FKB327-FKB327-FKB327 FKB327-Humira-FKB327 Humira-FKB327-FKB327 Humira-Humira-FKB327
Hide Arm/Group Description:

Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to receive FKB327 in Study FKB327-003 (F-F).

Period II: From week 30 all subjects received FKB327 (F-F-F).

Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to receive the reference product Humira in Study FKB327-003 (F-H).

Period II: From week 30 all subjects received FKB327 (F-H-F).

Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to receive FKB327 in Study FKB327-003 (H-F).

Period II: From week 30 all subjects received FKB327 (H-F-F).

Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to receive the reference product Humira in Study FKB327-003 (H-H).

Period II: From week 30 all subjects received FKB327 (H-H-F).

Overall Number of Participants Analyzed 216 108 108 213
Mean (Full Range)
Unit of Measure: units on a scale
Baseline_002 Number Analyzed 215 participants 107 participants 108 participants 213 participants
6.02
(3.3 to 8.1)
6.12
(2.9 to 8.5)
5.99
(3.7 to 7.9)
6.11
(4.0 to 8.0)
Week 0 Number Analyzed 215 participants 108 participants 108 participants 213 participants
3.46
(1.2 to 7.3)
3.49
(1.2 to 7.4)
3.65
(1.2 to 7.2)
3.36
(1.2 to 7.0)
Week 0 change from Baseline Number Analyzed 214 participants 107 participants 108 participants 213 participants
-2.56
(-5.7 to 1.0)
-2.63
(-6.4 to 1.2)
-2.33
(-5.4 to 0.9)
-2.75
(-5.7 to 1.3)
Week 4 Number Analyzed 208 participants 104 participants 105 participants 203 participants
3.33
(1.2 to 7.0)
3.37
(1.2 to 7.0)
3.53
(1.3 to 6.7)
3.29
(1.2 to 7.6)
Week 4 change from Baseline Number Analyzed 207 participants 103 participants 105 participants 203 participants
-2.64
(-6.1 to 1.8)
-2.76
(-6.9 to 0.9)
-2.48
(-4.9 to 1.6)
-2.81
(-6.1 to 1.8)
Week 8 Number Analyzed 202 participants 103 participants 104 participants 204 participants
3.28
(1.2 to 7.2)
3.37
(1.2 to 6.9)
3.51
(1.2 to 6.6)
3.25
(1.2 to 7.1)
Week 8 change from Baseline Number Analyzed 201 participants 102 participants 104 participants 204 participants
-2.72
(-5.9 to 2.7)
-2.74
(-6.9 to 0.8)
-2.47
(-4.8 to 0.9)
-2.84
(-5.8 to -0.2)
Week 12 Number Analyzed 200 participants 102 participants 103 participants 203 participants
3.31
(1.2 to 6.9)
3.30
(1.2 to 7.1)
3.40
(1.3 to 6.2)
3.21
(1.2 to 6.5)
Week 12 change from Baseline Number Analyzed 199 participants 101 participants 103 participants 203 participants
-2.70
(-5.9 to 0.8)
-2.80
(-6.9 to 0.3)
-2.57
(-4.9 to 0.5)
-2.88
(-5.8 to 0.9)
Week 24 Number Analyzed 197 participants 98 participants 95 participants 197 participants
3.13
(1.2 to 7.8)
3.27
(1.2 to 7.1)
3.40
(1.2 to 7.7)
3.07
(1.2 to 7.5)
Week 24 change from Baseline Number Analyzed 196 participants 97 participants 95 participants 197 participants
-2.89
(-6.1 to 1.3)
-2.86
(-6.7 to 0.9)
-2.57
(-5.4 to 1.7)
-3.04
(-6.0 to -0.0)
Period II: Week 30 Number Analyzed 183 participants 99 participants 92 participants 189 participants
3.04
(1.2 to 7.1)
3.28
(1.2 to 7.1)
3.20
(1.3 to 6.3)
3.13
(1.2 to 7.4)
Week 30 change from Baseline Number Analyzed 182 participants 98 participants 92 participants 189 participants
-2.99
(-6.1 to 0.3)
-2.84
(-6.6 to 0.5)
-2.78
(-5.3 to 0.4)
-2.95
(-6.2 to 1.9)
Week 42 Number Analyzed 184 participants 96 participants 90 participants 187 participants
3.05
(1.2 to 6.8)
3.28
(1.2 to 6.1)
3.08
(1.3 to 6.0)
3.07
(1.2 to 7.3)
week 42 change from Baseline Number Analyzed 183 participants 95 participants 90 participants 187 participants
-2.97
(-5.6 to 0.9)
-2.83
(-6.2 to -0.2)
-2.88
(-5.5 to -0.0)
-3.01
(-5.8 to 0.6)
Week 54 Number Analyzed 180 participants 92 participants 89 participants 180 participants
3.04
(1.2 to 7.5)
3.22
(1.2 to 6.2)
3.26
(1.2 to 6.2)
2.96
(1.2 to 6.8)
Week 54 change from Baseline Number Analyzed 179 participants 91 participants 89 participants 180 participants
-2.99
(-5.9 to 0.4)
-2.90
(-6.2 to 0.9)
-2.70
(-5.4 to 0.4)
-3.12
(-5.6 to 1.6)
Week 66 Number Analyzed 174 participants 89 participants 84 participants 175 participants
2.96
(1.2 to 7.0)
3.17
(1.2 to 5.7)
3.09
(1.3 to 5.6)
2.91
(1.2 to 6.9)
Week 66 change from Baseline Number Analyzed 173 participants 88 participants 84 participants 175 participants
-3.09
(-5.9 to 0.3)
-2.96
(-6.9 to -0.0)
-2.83
(-5.5 to 0.8)
-3.15
(-5.6 to 0.2)
Week 76 Number Analyzed 174 participants 90 participants 81 participants 172 participants
2.97
(1.2 to 7.8)
3.02
(1.2 to 6.2)
3.12
(1.3 to 7.0)
2.94
(1.2 to 6.4)
Week 76 change from Baseline Number Analyzed 173 participants 89 participants 81 participants 172 participants
-3.04
(-5.9 to 0.2)
-3.11
(-6.1 to 0.4)
-2.79
(-5.5 to 1.0)
-3.14
(-5.7 to -0.2)
Week 80 Number Analyzed 172 participants 88 participants 81 participants 170 participants
2.98
(1.2 to 7.1)
3.09
(1.2 to 6.9)
3.25
(1.2 to 6.7)
3.06
(1.2 to 6.7)
Week 80 change from Baseline Number Analyzed 171 participants 87 participants 81 participants 170 participants
-3.05
(-6.2 to 2.2)
-3.05
(-6.9 to -0.3)
-2.66
(-5.4 to 0.2)
-3.02
(-5.8 to 0.2)
11.Secondary Outcome
Title American College of Rheumatology 20 (ACR20) Response Rates From Baseline as a Measure of Efficacy
Hide Description

An ACR20 response means that the patient achieved a 20% improvement in Tender Joint Count (TJC) and Swollen Joint Count (SJC) and a 20% improvement in at least 3 of the other 5 Core Data Set elements listed below:

  • Acute phase reactant (C-reactive protein, CRP) A high level of CRP in the blood is a marker of inflammation.
  • Patient global assessment of disease activity assessed on a Visual Analog Scale (VAS) ranging from very well to extremely bad was assessed on a 100 point scale. (from 0 to 100)
  • Physician global assessment of disease activity assessed on a VAS ranging from very low to very high was assessed on 100 point scale
  • Patient pain scale assessed on a VAS ranging from very well to extremely bad was assessed on 100 point scale
  • Disability/functional questionnaire (patient completed Heath Assessment Questionnaire Disability Index (HAQ-DI)) A higher response rate is a better outcome. The minimum possible value is 0% and the maximum possible value is 100%
Time Frame From Week 0 to Week 80
Hide Outcome Measure Data
Hide Analysis Population Description
Number of patients at a given time-point with an observed ACR20 score defined as a 20% improvement in tender and swollen joints and at least 3 out of 5 other indicators from Baseline_002 (Week 0 of FKB327-002; NCT02260791)
Arm/Group Title FKB327-FKB327-FKB327 FKB327-Humira-FKB327 Humira-FKB327-FKB327 Humira-Humira-FKB327
Hide Arm/Group Description:

Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to FKB327 in Period I of study FKB327-003 (F-F).

Period II: From week 30 all subjects received FKB327 (F-F-F).

Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study FKB327-002 and were re-randomized to the reference product, Humira, during Period I of study FKB327-003 (F-H).

Period II: From week 30 all subjects received FKB327 (F-H-F).

Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to FKB327 during Period I of study FKB327-003 (H-F).

Period II: From week 30 all subjects received FKB327 (H-F-F).

Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002, and were re-randomized to the reference product Humira during Period I of study FKB327-003 (H-H).

Period II: From week 30 all subjects received FKB327 (H-H-F).

Overall Number of Participants Analyzed 216 108 108 213
Measure Type: Count of Participants
Unit of Measure: Participants
Week 0 Number Analyzed 216 participants 108 participants 108 participants 212 participants
163
  75.5%
87
  80.6%
82
  75.9%
175
  82.5%
Week 4 Number Analyzed 210 participants 105 participants 107 participants 208 participants
171
  81.4%
83
  79.0%
84
  78.5%
165
  79.3%
Week 8 Number Analyzed 205 participants 103 participants 104 participants 204 participants
160
  78.0%
84
  81.6%
79
  76.0%
173
  84.8%
Week 12 Number Analyzed 203 participants 102 participants 103 participants 203 participants
160
  78.8%
89
  87.3%
82
  79.6%
171
  84.2%
Week 24 Number Analyzed 197 participants 100 participants 95 participants 198 participants
162
  82.2%
83
  83.0%
75
  78.9%
176
  88.9%
Period II: Week 30 Number Analyzed 185 participants 98 participants 92 participants 189 participants
154
  83.2%
82
  83.7%
79
  85.9%
158
  83.6%
Week 42 Number Analyzed 184 participants 96 participants 90 participants 187 participants
156
  84.8%
79
  82.3%
81
  90.0%
164
  87.7%
Week 54 Number Analyzed 180 participants 93 participants 90 participants 180 participants
149
  82.8%
78
  83.9%
77
  85.6%
152
  84.4%
Week 66 Number Analyzed 174 participants 89 participants 84 participants 175 participants
140
  80.5%
73
  82.0%
74
  88.1%
150
  85.7%
Week 76 Number Analyzed 175 participants 90 participants 81 participants 172 participants
140
  80.0%
77
  85.6%
71
  87.7%
147
  85.5%
Week 80/EOS Number Analyzed 173 participants 88 participants 81 participants 170 participants
133
  76.9%
72
  81.8%
62
  76.5%
140
  82.4%
12.Secondary Outcome
Title American College of Rheumatology 50 (ACR50) Response Rates From Baseline as a Measure of Efficacy
Hide Description

An ACR50 response means that the patient achieved a 50% improvement in Tender Joint Count (TJC) and Swollen Joint Count (SJC) and in at least 3 of the other 5 Core Data Set elements listed below:

  • Acute phase reactant (C-reactive protein, CRP) A high level of CRP in the blood is a marker of inflammation.
  • Patient global assessment of disease activity assessed on a Visual Analog Scale (VAS) ranging from very well to extremely bad was assessed on a 100 point scale. (from 0 to 100)
  • Physician global assessment of disease activity assessed on a VAS ranging from very low to very high was assessed on 100 point scale
  • Patient pain scale assessed on a VAS ranging from very well to extremely bad was assessed on 100 point scale
  • Disability/functional questionnaire (patient completed Heath Assessment Questionnaire Disability Index (HAQ-DI)) A higher response rate is a better outcome. The minimum possible value is 0% and the maximum possible value is 100%
Time Frame From Week 0 to Week 80
Hide Outcome Measure Data
Hide Analysis Population Description
Number of patients at a given time-point with an observed ACR50 score defined as a 50% improvement in tender and swollen joints and at least in 3 out of 5 other indicators from Baseline_002 (Week 0 of FKB327-002; NCT02260791)
Arm/Group Title FKB327-FKB327-FKB327 FKB327-Humira-FKB327 Humira-FKB327-FKB327 Humira-Humira-FKB327
Hide Arm/Group Description:

Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to FKB327 in Period I of study FKB327-003 (F-F).

Period II: From week 30 all subjects received FKB327 (F-F-F).

Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study FKB327-002 and were re-randomized to the reference product, Humira, during Period I of study FKB327-003 (F-H).

Period II: From week 30 all subjects received FKB327 (F-H-F).

Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to FKB327 during Period I of study FKB327-003 (H-F).

Period II: From week 30 all subjects received FKB327 (H-F-F).

Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002, and were re-randomized to the reference product Humira during Period I of study FKB327-003 (H-H).

Period II: From week 30 all subjects received FKB327 (H-H-F).

Overall Number of Participants Analyzed 216 108 108 213
Measure Type: Count of Participants
Unit of Measure: Participants
Week 0 Number Analyzed 215 participants 108 participants 108 participants 212 participants
104
  48.4%
52
  48.1%
50
  46.3%
109
  51.4%
Week 4 Number Analyzed 211 participants 105 participants 107 participants 208 participants
110
  52.1%
50
  47.6%
52
  48.6%
115
  55.3%
Week 8 Number Analyzed 205 participants 103 participants 104 participants 204 participants
106
  51.7%
53
  51.5%
51
  49.0%
124
  60.8%
Week 12 Number Analyzed 202 participants 102 participants 103 participants 203 participants
106
  52.5%
53
  52.0%
55
  53.4%
131
  64.5%
Week 24 Number Analyzed 197 participants 100 participants 95 participants 199 participants
114
  57.9%
56
  56.0%
49
  51.6%
127
  63.8%
Period II: Week 30 Number Analyzed 185 participants 98 participants 92 participants 189 participants
112
  60.5%
57
  58.2%
50
  54.3%
113
  59.8%
Week 42 Number Analyzed 184 participants 96 participants 90 participants 187 participants
113
  61.4%
47
  49.0%
54
  60.0%
115
  61.5%
Week 54 Number Analyzed 180 participants 92 participants 90 participants 180 participants
106
  58.9%
47
  51.1%
44
  48.9%
110
  61.1%
Week 66 Number Analyzed 174 participants 89 participants 84 participants 175 participants
110
  63.2%
48
  53.9%
46
  54.8%
114
  65.1%
Week 76 Number Analyzed 175 participants 90 participants 81 participants 173 participants
108
  61.7%
59
  65.6%
43
  53.1%
108
  62.4%
Week 80/EOS Number Analyzed 173 participants 88 participants 81 participants 170 participants
102
  59.0%
47
  53.4%
43
  53.1%
112
  65.9%
13.Secondary Outcome
Title American College of Rheumatology 70 (ACR70) Response Rates From Baseline as a Measure of Efficacy
Hide Description

An ACR70 response means that the patient achieved a 70% improvement in Tender Joint Count (TJC) and Swollen Joint Count (SJC) and in at least 3 of the other 5 Core Data Set elements listed below:

  • Acute phase reactant (C-reactive protein,CRP) A high level of CRP in the blood is a marker of inflammation.
  • Patient global assessment of disease activity assessed on a Visual Analog Scale (VAS) ranging from very well to extremely bad was assessed on a 100 point scale. (from 0 to 100)
  • Physician global assessment of disease activity assessed on a VAS ranging from very low to very high was assessed on 100 point scale
  • Patient pain scale assessed on a VAS ranging from very well to extremely bad was assessed on 100 point scale
  • Disability/functional questionnaire (patient completed Heath Assessment Questionnaire Disability Index (HAQ-DI)) A higher response rate is a better outcome. The minimum possible value is 0% and the maximum possible value is 100%
Time Frame From Week 0 to Week 80
Hide Outcome Measure Data
Hide Analysis Population Description
Number of patients at a given time-point with an observed ACR70 score defined as a 70% improvement in tender and swollen joints and at least 3 out of 5 other indicators from Baseline_002 (Week 0 of FKB327-002; NCT02260791)
Arm/Group Title FKB327-FKB327-FKB327 FKB327-Humira-FKB327 Humira-FKB327-FKB327 Humira-Humira-FKB327
Hide Arm/Group Description:

Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to FKB327 in Period I of study FKB327-003 (F-F).

Period II: From week 30 all subjects received FKB327 (F-F-F).

Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study FKB327-002 and were re-randomized to the reference product, Humira, during Period I of study FKB327-003 (F-H).

Period II: From week 30 all subjects received FKB327 (F-H-F).

Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to FKB327 during Period I of study FKB327-003 (H-F).

Period II: From week 30 all subjects received FKB327 (H-F-F).

Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002, and were re-randomized to the reference product Humira during Period I of study FKB327-003 (H-H).

Period II: From week 30 all subjects received FKB327 (H-H-F).

Overall Number of Participants Analyzed 216 108 108 213
Measure Type: Count of Participants
Unit of Measure: Participants
Week 0 Number Analyzed 216 participants 108 participants 108 participants 212 participants
45
  20.8%
23
  21.3%
23
  21.3%
56
  26.4%
Week 4 Number Analyzed 211 participants 104 participants 107 participants 207 participants
54
  25.6%
30
  28.8%
29
  27.1%
54
  26.1%
Week 8 Number Analyzed 204 participants 103 participants 104 participants 204 participants
61
  29.9%
29
  28.2%
26
  25.0%
72
  35.3%
Week 12 Number Analyzed 203 participants 102 participants 103 participants 203 participants
59
  29.1%
28
  27.5%
29
  28.2%
69
  34.0%
Week 24 Number Analyzed 197 participants 99 participants 95 participants 199 participants
65
  33.0%
30
  30.3%
25
  26.3%
80
  40.2%
Period II: Week 30 Number Analyzed 185 participants 99 participants 92 participants 189 participants
67
  36.2%
33
  33.3%
28
  30.4%
74
  39.2%
Week 42 Number Analyzed 184 participants 96 participants 90 participants 187 participants
72
  39.1%
27
  28.1%
26
  28.9%
74
  39.6%
Week 54 Number Analyzed 180 participants 93 participants 90 participants 180 participants
69
  38.3%
29
  31.2%
19
  21.1%
69
  38.3%
Week 66 Number Analyzed 174 participants 89 participants 84 participants 175 participants
69
  39.7%
29
  32.6%
25
  29.8%
73
  41.7%
Week 76 Number Analyzed 175 participants 90 participants 81 participants 173 participants
72
  41.1%
31
  34.4%
20
  24.7%
71
  41.0%
Week 80/EOS Number Analyzed 172 participants 88 participants 81 participants 170 participants
64
  37.2%
27
  30.7%
25
  30.9%
69
  40.6%
14.Other Pre-specified Outcome
Title Proportion of Patients Developing Anti-drug Antibodies (ADAs)
Hide Description

Blood samples for assessment of Anti-Drug antibodies (ADA) were collected prior to dosing (trough samples) at Baseline (Week 0) and at Weeks 12, 24, 30, 54, 76 and 80/EOS.

All ADA activity was listed and summarized for each treatment sequence by time point during the overall treatment period as well as by treatment group for each period (Period I and Period II). Descriptive statistics included absolute counts (n) and percentage (%).

Time Frame From Week 0 to Week 80
Hide Outcome Measure Data
Hide Analysis Population Description
Number of patients who had an assay result of positive Anti-Drug Antibodies at given time-points.
Arm/Group Title FKB327-FKB327-FKB327 FKB327-Humira-FKB327 Humira-FKB327-FKB327 Humira-Humira-FKB327
Hide Arm/Group Description:

Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to FKB327 in Period I of study FKB327-003 (F-F).

Period II: From week 30 all subjects received FKB327 (F-F-F).

Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study FKB327-002 and were re-randomized to the reference product Humira during Period I of study FKB327-003 (F-H).

Period II: From week 30 all subjects received FKB327 (F-H-F).

Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to FKB327 during Period I of study FKB327-003 (H-F).

Period II: From week 30 all subjects received FKB327 (H-F-F).

Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002, and were re-randomized to the reference product Humira during Period I of study FKB327-003 (H-H).

Period II: From week 30 all subjects received FKB327 (H-H-F).

Overall Number of Participants Analyzed 216 108 108 213
Measure Type: Count of Participants
Unit of Measure: Participants
Week 0 Number Analyzed 216 participants 108 participants 108 participants 212 participants
133
  61.6%
69
  63.9%
67
  62.0%
123
  58.0%
Week 12 Number Analyzed 202 participants 103 participants 103 participants 202 participants
107
  53.0%
60
  58.3%
54
  52.4%
101
  50.0%
Week 24 Number Analyzed 197 participants 100 participants 96 participants 199 participants
99
  50.3%
58
  58.0%
47
  49.0%
100
  50.3%
Period II: Week 30 Number Analyzed 187 participants 100 participants 93 participants 190 participants
97
  51.9%
61
  61.0%
42
  45.2%
98
  51.6%
Week 54 Number Analyzed 181 participants 93 participants 89 participants 181 participants
103
  56.9%
49
  52.7%
41
  46.1%
77
  42.5%
Week 76 Number Analyzed 176 participants 90 participants 81 participants 174 participants
90
  51.1%
49
  54.4%
39
  48.1%
74
  42.5%
Week 80/EOS Number Analyzed 173 participants 87 participants 80 participants 170 participants
91
  52.6%
48
  55.2%
37
  46.3%
72
  42.4%
Last Sampling Day Number Analyzed 216 participants 108 participants 108 participants 213 participants
115
  53.2%
63
  58.3%
49
  45.4%
99
  46.5%
15.Other Pre-specified Outcome
Title Trough Adalimumab Concentration
Hide Description Blood samples for the quantification of adalimumab concentration in serum were collected prior to dosing (trough samples) at Baseline (Week 0), and at weeks 12, 24 , 30, 54, 76 and 80/EOS.
Time Frame From Week 0 to Week 80
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis of Serum Concentration Data (ng/mL). Repeated measure of pharmacokinetic(s) (PK) trough concentrations at given time-points.
Arm/Group Title FKB327-FKB327-FKB327 FKB327-Humira-FKB327 Humira-FKB327-FKB327 Humira-Humira-FKB327
Hide Arm/Group Description:

Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to FKB327 in Period I of study FKB327-003 (F-F).

Period II: From week 30 all subjects received FKB327 (F-F-F).

Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study FKB327-002 and were re-randomized to the reference product, Humira, during Period I of study FKB327-003 (F-H).

Period II: From week 30 all subjects received FKB327 (F-H-F).

Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to FKB327 during Period I of study FKB327-003 (H-F).

Period II: From week 30 all subjects received FKB327 (H-F-F).

Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002, and were re-randomized to the reference product Humira during Period I of study FKB327-003 (H-H).

Period I: From week 30 all subjects received FKB327 (H-H-F).

Overall Number of Participants Analyzed 208 105 107 210
Mean (Standard Deviation)
Unit of Measure: ng/mL
Week 0 Number Analyzed 208 participants 105 participants 107 participants 209 participants
6500  (4640) 6000  (4520) 5170  (3440) 5720  (3470)
Week 12 Number Analyzed 202 participants 103 participants 103 participants 202 participants
6310  (4720) 5380  (4150) 6180  (3970) 6010  (3730)
Week 24 Number Analyzed 197 participants 100 participants 95 participants 199 participants
5970  (4500) 5100  (3990) 6320  (4320) 5950  (3750)
Period II: Week 30 Number Analyzed 187 participants 100 participants 93 participants 190 participants
6000  (4450) 4790  (4290) 5730  (3750) 5750  (3680)
Week 54 Number Analyzed 180 participants 93 participants 89 participants 181 participants
6090  (4620) 5830  (4290) 5840  (4100) 6620  (3920)
Week 76 Number Analyzed 176 participants 90 participants 80 participants 173 participants
6460  (4140) 5900  (4020) 6070  (4350) 6730  (4080)
Week 80 Number Analyzed 173 participants 87 participants 80 participants 170 participants
4320  (3130) 4000  (3280) 4060  (3310) 4520  (3100)
Time Frame Overall Adverse Events and Serious Adverse Events were collected and monitored up to week 80 for subjects completing the study and 4 weeks after an Early Termination Visit. Period I - from signing of informed consent up to week 30. During this period subjects received either FKB327 or the reference product Humira. Period II: From week 30 to week 76 all subjects received FKB327 hence the maximum duration of FKB327 treatment was about 2.5 times greater compared to the Humira (581 vs 222 days).
Adverse Event Reporting Description The overall exposure in patient-years was nearly 4 times greater for FKB327 (673.7) compared to Humira (175.4), due to patients switching from Humira to FKB327 for Period II, which should be taken into account when reviewing the safety results where FKB327 and Humira are directly compared.
 
Arm/Group Title FKB327 Humira®
Hide Arm/Group Description FKB327: Solution of FKB327 for subcutaneous injection administered in a dose of 40 mg/0.8mL every 2 weeks for 28 weeks. From week 30 all patients were transferred to receive FKB327 40 mg/0.8 mL every other week presented in an auto-injector (AI) or a pre-filled syringe (PFS). Some patients received continuous FKB327 40 mg every other week by subcutaneous injection for up to 76 weeks. Humira®: Solution of Humira® for subcutaneous injection administered in a dose of 40 mg every 2 weeks for 28 weeks. From week 30 to week 76 all patients were transferred to receive FKB327 40 mg/0.8 mL in a pre-filled syringe (PFS) every other week by subcutaneous injection.
All-Cause Mortality
FKB327 Humira®
Affected / at Risk (%) Affected / at Risk (%)
Total   3/614 (0.49%)      1/321 (0.31%)    
Hide Serious Adverse Events
FKB327 Humira®
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   43/614 (7.00%)      14/321 (4.36%)    
Cardiac disorders     
Acute myocardial infarction  1  2/614 (0.33%)  2 0/321 (0.00%)  0
Angina unstable  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Cardiac failure congestive  1  0/614 (0.00%)  0 1/321 (0.31%)  2
Myocardial infarction  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Gastrointestinal disorders     
Oesophageal rupture  1  1/614 (0.16%)  1 0/321 (0.00%)  0
General disorders     
Death  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Non-cardiac chest pain  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Pyrexia  1  0/614 (0.00%)  0 1/321 (0.31%)  1
Sudden death  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Hepatobiliary disorders     
Cholangitis  1  0/614 (0.00%)  0 1/321 (0.31%)  1
Cholecystitis chronic  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Cholelithiasis  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Hepatocellular injury  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Infections and infestations     
Pneumonia  1  4/614 (0.65%)  4 1/321 (0.31%)  1
Pyelonephritis acute  1  4/614 (0.65%)  4 1/321 (0.31%)  1
Bronchitis  1  1/614 (0.16%)  1 1/321 (0.31%)  1
Pyelonephritis  1  2/614 (0.33%)  2 0/321 (0.00%)  0
Sepsis  1  2/614 (0.33%)  2 0/321 (0.00%)  0
Appendicitis  1  0/614 (0.00%)  0 1/321 (0.31%)  1
Erysipelas  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Meningitis  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Pulmonary mycosis  1  0/614 (0.00%)  0 1/321 (0.31%)  1
Urinary tract infection  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Injury, poisoning and procedural complications     
Femur fracture  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Fracture  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Maternal exposure during pregnancy  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Muscle rupture  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Tendon rupture  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Metabolism and nutrition disorders     
Hyponatraemia  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Back pain  1  2/614 (0.33%)  2 0/321 (0.00%)  0
Osteoarthritis  1  1/614 (0.16%)  1 1/321 (0.31%)  1
Back disorder  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Bursitis  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Intervertebral disc degeneration  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Rheumatoid arthritis  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Rotator cuff syndrome  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Spinal column stenosis  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Spondylolisthesis  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Synovitis  1  0/614 (0.00%)  0 1/321 (0.31%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Breast cancer  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Cervix carcinoma  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Nervous system disorders     
Anterior spinal artery syndrome  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Cerebrovascular accident  1  0/614 (0.00%)  0 1/321 (0.31%)  1
Sciatica  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Pregnancy, puerperium and perinatal conditions     
Pregnancy  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Renal and urinary disorders     
Calculus urinary  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Hydronephrosis  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Nephrolithiasis  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Renal failure chronic  1  0/614 (0.00%)  0 1/321 (0.31%)  1
Reproductive system and breast disorders     
Cervical dysplasia  1  2/614 (0.33%)  2 0/321 (0.00%)  0
Endometrial hyperplasia  1  1/614 (0.16%)  1 1/321 (0.31%)  1
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Lung disorder  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Pulmonary mass  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Surgical and medical procedures     
Hip arthroplasty  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Joint surgery  1  0/614 (0.00%)  0 1/321 (0.31%)  1
Knee Arthroplasty  1  0/614 (0.00%)  0 1/321 (0.31%)  1
Synovectomy  1  1/614 (0.16%)  1 0/321 (0.00%)  0
Vascular disorders     
Lymphostatis  1  1/614 (0.16%)  1 0/321 (0.00%)  0
1
Term from vocabulary, MedDRA (17.1)
Indicates events were collected by systematic assessment
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   125/614 (20.36%)      46/321 (14.33%)    
Infections and infestations     
Nasopharyngitis  1  68/614 (11.07%)  77 22/321 (6.85%)  25
Bronchitis  1  32/614 (5.21%)  34 14/321 (4.36%)  15
Musculoskeletal and connective tissue disorders     
Rheumatoid Arthritis  1  37/614 (6.03%)  53 15/321 (4.67%)  18
1
Term from vocabulary, MedDRA (17.1)
Indicates events were collected by 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 Investigator an Sponsor, in accordance with recognized principles of scientific collaboration.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Clinical Trial Information
Organization: Fujifilm Kyowa Kirin Biologics Co., Ltd., EU Branch
Phone: 0044 1896 668 173
EMail: Clinical-Trials@fk-b.com
Layout table for additonal information
Responsible Party: Fujifilm Kyowa Kirin Biologics Co., Ltd.
ClinicalTrials.gov Identifier: NCT02405780    
Other Study ID Numbers: FKB327-003
First Submitted: March 17, 2015
First Posted: April 1, 2015
Results First Submitted: January 18, 2019
Results First Posted: March 26, 2019
Last Update Posted: March 26, 2019