A Study to Compare FKB327 Long-term Safety, Efficacy and... | NCT02405780

Status Module

Description Module

Label	Type	Description	Intervention Names
FKB327	Experimental	Patients will receive the drug 40 mg every other week by subcutaneous injection. The treatment period may continue for 76 weeks.	Drug: FKB327
Humira®	Active Comparator	Patients will receive the drug 40 mg every other week by subcutaneous injection. The treatment period may continue for 76 weeks.	Drug: Humira®

Name	Type	Description	Arm Group Labels	Other Names
FKB327	Drug	Solution of FKB327 for subcutaneous injection administered in a dose of 40 mg every 2 weeks for 28 weeks. Patients may continue to receive FKB327 40 mg every other week by subcutaneous injection for up to 76 weeks.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Patients With Adverse Events as a Measure of Safety Per Treatment Group in Period I	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.	Period I: from Week 0 up until Week 30;
Number of Patients With Adverse Events as a Measure of Safety in Period II - Single Treatment Period	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.	Period II: from Week 30 up to Week 80
Number of Patients With Serious Adverse Events as a Measure of Safety Per Treatment Group in Period I	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.	Period I: from Week 0 up until Week 30
Number of Patients With Serious Adverse Events as a Measure of Safety in Period II - Single Treatment Period	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.

Secondary Outcomes

Measure	Description	Time Frame
Changes in Disease Activity Score 28 Based on C Reactive Protein (DAS28 CRP) Score Compared to Baseline as a Measure of Efficacy	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).

Other Outcomes

Measure	Description	Time Frame
Proportion of Patients Developing Anti-drug Antibodies (ADAs)	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 (%).

Eligibility Module

Name	Affiliation	Role
Josephine Glover, MD	Coephycient Pharmaceutical Consultancy	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Peoria	Arizona	85381	United States
Research Site

PubMed Identifier	Type	Citation	Retractions
33263165	Derived	Huizinga TWJ, Torii Y, Muniz R. Adalimumab Biosimilars in the Treatment of Rheumatoid Arthritis: A Systematic Review of the Evidence for Biosimilarity. Rheumatol Ther. 2021 Mar;8(1):41-61. doi: 10.1007/s40744-020-00259-8. Epub 2020 Dec 1.
31831079	Derived	Genovese MC, Glover J, Greenwald M, Porawska W, El Khouri EC, Dokoupilova E, Vargas JI, Stanislavchuk M, Kellner H, Baranova E, Matsunaga N, Alten R. FKB327, an adalimumab biosimilar, versus the reference product: results of a randomized, Phase III, double-blind study, and its open-label extension. Arthritis Res Ther. 2019 Dec 12;21(1):281. doi: 10.1186/s13075-019-2046-0.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	FKB327-FKB327-FKB327	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).
FG001	FKB327-Humira-FKB327

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Apr 15, 2016	Jan 18, 2019

Arm/Group Information

ID	Title	Description
BG000	FKB327-FKB327	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.
BG001	FKB327-Humira	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.
BG002	Humira-FKB327	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.
BG003	Humira-Humira	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.
BG004	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Patients With Adverse Events as a Measure of Safety Per Treatment Group in Period I

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.

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.

Posted

Number

participants

Period I: from Week 0 up until Week 30;

ID	Title	Description
OG000	FKB327-FKB327	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).
OG001	FKB327-Humira	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).
OG002	Humira-FKB327	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).
OG003	Humira-Humira	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).

Units	Counts
Participants	OG000216 OG001108 OG002108 OG003

Title

Denominators

Categories

Death

Title	Measurements
	OG0000 OG0010 OG0021 OG003

Primary

Number of Patients With Adverse Events as a Measure of Safety in Period II - Single Treatment Period

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.

Posted

Count of Participants

Participants

Period II: from Week 30 up to Week 80

ID	Title	Description
OG000	FKB327	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)

Units	Counts
Participants	OG000

Primary

Number of Patients With Serious Adverse Events as a Measure of Safety Per Treatment Group in Period I

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.

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.

Posted

Number

participants

Period I: from Week 0 up until Week 30

ID	Title	Description
OG000	FKB327-FKB327	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).
OG001	FKB327-Humira	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).

Primary

Number of Patients With Serious Adverse Events as a Measure of Safety in Period II - Single Treatment Period

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.

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.

Posted

Count of Participants

Participants

Period II: from Week 30 up to Week 80

ID	Title	Description
OG000	FKB327	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)

Units	Counts
Participants

Primary

Changes in Vital Signs as a Measure of Safety - Systolic Blood Pressure

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.

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.

Posted

Median

Full Range

mmHg

From Week 0 to Week 80

ID	Title	Description
OG000	FKB327-FKB327-FKB327	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).
OG001	FKB327-Humira-FKB327	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).

Primary

Changes in Vital Signs as a Measure of Safety - Diastolic Blood Pressure

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.

Posted

Median

Full Range

mmHg

From Week 0 to Week 80

ID	Title	Description
OG000	FKB327-FKB327-FKB327	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).
OG001	FKB327-Humira-FKB327	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).

Primary

Changes in Vital Signs as a Measure of Safety - Pulse Rate

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.

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.

Posted

Median

Full Range

Beats per minute (bpm)

From Week 0 to Week 80

ID	Title	Description
OG000	FKB327-FKB327-FKB327	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).
OG001	FKB327-Humira-FKB327	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).

Primary

Changes in Vital Signs as a Measure of Safety - Temperature Measurements

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).

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.

Posted

Median

Full Range

Centigrades

From Week 0 to Week 80

ID	Title	Description
OG000	FKB327-FKB327-FKB327	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).
OG001	FKB327-Humira-FKB327	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).

Primary

Summary of Most Common Clinical Significant Laboratory Parameters Reported as Adverse Events (Reported by ≥1% of the Patients)

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.

Posted

Number

participants

From Week 0 to Week 80

ID	Title	Description
OG000	FKB327-FKB327	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).
OG001	FKB327-Humira	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).
OG002	Humira-FKB327	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).

Secondary

Changes in Disease Activity Score 28 Based on C Reactive Protein (DAS28 CRP) Score Compared to Baseline as a Measure of Efficacy

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).

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)

Posted

Mean

Full Range

units on a scale

From Week 0 of FKB327-002 to Week 80

ID	Title	Description
OG000	FKB327-FKB327-FKB327	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).
OG001	FKB327-Humira-FKB327

Secondary

American College of Rheumatology 20 (ACR20) Response Rates From Baseline as a Measure of Efficacy

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%

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)

Posted

Count of Participants

Participants

From Week 0 to Week 80

ID	Title	Description
OG000	FKB327-FKB327-FKB327	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).

Secondary

American College of Rheumatology 50 (ACR50) Response Rates From Baseline as a Measure of Efficacy

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%

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)

Posted

Count of Participants

Participants

From Week 0 to Week 80

ID	Title	Description
OG000	FKB327-FKB327-FKB327	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).

Secondary

American College of Rheumatology 70 (ACR70) Response Rates From Baseline as a Measure of Efficacy

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%

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)

Posted

Count of Participants

Participants

From Week 0 to Week 80

ID	Title	Description
OG000	FKB327-FKB327-FKB327	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).

Other Pre-specified

Proportion of Patients Developing Anti-drug Antibodies (ADAs)

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 (%).

Number of patients who had an assay result of positive Anti-Drug Antibodies at given time-points.

Posted

Count of Participants

Participants

From Week 0 to Week 80

ID	Title	Description
OG000	FKB327-FKB327-FKB327	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).
OG001	FKB327-Humira-FKB327	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).
OG002	Humira-FKB327-FKB327

Other Pre-specified

Trough Adalimumab Concentration

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.

Analysis of Serum Concentration Data (ng/mL). Repeated measure of pharmacokinetic(s) (PK) trough concentrations at given time-points.

Posted

Mean

Standard Deviation

ng/mL

From Week 0 to Week 80

ID	Title	Description
OG000	FKB327-FKB327-FKB327	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).
OG001	FKB327-Humira-FKB327	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).
OG002	Humira-FKB327-FKB327	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).

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	FKB327	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.	3	614	43	614	125	614
EG001	Humira®	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.	1	321	14	321	46	321

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute myocardial infarction	Cardiac disorders	MedDRA (17.1)	Systematic Assessment	EG0002 events2 affected614 at risk EG0010 events0 affected321 at risk
Angina unstable	Cardiac disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected614 at risk EG0012 events1 affected321 at risk
Myocardial infarction	Cardiac disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Oesophageal rupture	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Death	General disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Non-cardiac chest pain	General disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Pyrexia	General disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected614 at risk EG0011 events1 affected321 at risk
Sudden death	General disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Cholangitis	Hepatobiliary disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected614 at risk EG0011 events1 affected321 at risk
Cholecystitis chronic	Hepatobiliary disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Hepatocellular injury	Hepatobiliary disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Pneumonia	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0004 events4 affected614 at risk EG0011 events1 affected321 at risk
Pyelonephritis acute	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0004 events4 affected614 at risk EG0011 events1 affected321 at risk
Bronchitis	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0011 events1 affected321 at risk
Pyelonephritis	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0002 events2 affected614 at risk EG0010 events0 affected321 at risk
Sepsis	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0002 events2 affected614 at risk EG0010 events0 affected321 at risk
Appendicitis	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected614 at risk EG0011 events1 affected321 at risk
Erysipelas	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Meningitis	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Pulmonary mycosis	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected614 at risk EG0011 events1 affected321 at risk
Urinary tract infection	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Fracture	Injury, poisoning and procedural complications	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Maternal exposure during pregnancy	Injury, poisoning and procedural complications	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Muscle rupture	Injury, poisoning and procedural complications	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Tendon rupture	Injury, poisoning and procedural complications	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Systematic Assessment	EG0002 events2 affected614 at risk EG0010 events0 affected321 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0011 events1 affected321 at risk
Back disorder	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Bursitis	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Intervertebral disc degeneration	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Rheumatoid arthritis	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Rotator cuff syndrome	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Spinal column stenosis	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Spondylolisthesis	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Synovitis	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected614 at risk EG0011 events1 affected321 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Cervix carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Anterior spinal artery syndrome	Nervous system disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected614 at risk EG0011 events1 affected321 at risk
Sciatica	Nervous system disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Pregnancy	Pregnancy, puerperium and perinatal conditions	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Calculus urinary	Renal and urinary disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Renal failure chronic	Renal and urinary disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected614 at risk EG0011 events1 affected321 at risk
Cervical dysplasia	Reproductive system and breast disorders	MedDRA (17.1)	Systematic Assessment	EG0002 events2 affected614 at risk EG0010 events0 affected321 at risk
Endometrial hyperplasia	Reproductive system and breast disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0011 events1 affected321 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Lung disorder	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Pulmonary mass	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Hip arthroplasty	Surgical and medical procedures	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Joint surgery	Surgical and medical procedures	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected614 at risk EG0011 events1 affected321 at risk
Knee Arthroplasty	Surgical and medical procedures	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected614 at risk EG0011 events1 affected321 at risk
Synovectomy	Surgical and medical procedures	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk
Lymphostatis	Vascular disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected321 at risk

ID	Term
D007592	Joint Diseases
D009140	Musculoskeletal Diseases
D012216	Rheumatic Diseases
D003240	Connective Tissue Diseases
D017437	Skin and Connective Tissue Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG00077 events68 affected614 at risk EG00125 events22 affected321 at risk
Bronchitis	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG00034 events32 affected614 at risk EG00115 events14 affected321 at risk
Rheumatoid Arthritis	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Systematic Assessment	EG00053 events37 affected614 at risk EG00118 events15 affected321 at risk

ID	Term
C000711167	FKB327
C000712789	adalimumab biosimilar HS016
D000068879	Adalimumab