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

Arthritis, Rheumatoid Clinical Trial

— ARABESC-OLE  

Official title:

An Open-label Extension Study to Compare the Long-term Efficacy, Safety, Immunogenicity and Pharmacokinetics of FKB327 and Humira® in Patients With Rheumatoid Arthritis on Concomitant Methotrexate

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02405780
• Other study ID #: FKB327-003
• Status: Completed
• Phase: Phase 3
• Start date: June 10, 2015
• Est. completion date: January 18, 2018

Study information

• Verified date: March 2019
• Source: Fujifilm Kyowa Kirin Biologics Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to compare the long-term safety, effectiveness and immunogenicity of FKB327 in comparison to Humira® in rheumatoid arthritis patients who have completed study FKB327-002 and have inadequate disease control on methotrexate.

Description:

The first period of this extension study was an open label, randomised, comparative, multi centre, 2 arm extension Phase 3 study in patients with RA who were taking a stable dose of MTX and who had continued from the preceding Study FKB327-002 (NCT02260791). The transition from Study FKB327-002 was ideally to occur without interruption: the Week 24 visit of Study FKB327-002 was to be on the same day as the Week 0 visit of Study FKB327-003. Patients who had received FKB327 in Study FKB327-002 received FKB327 or Humira in a 2:1 ratio and patients who had received Humira in Study FKB327-002 received Humira or FKB327 in a 2:1 ratio (Period I). The second period of the study was an open label, single arm extension in which all patients received FKB327 treatment from Week 30 to Week 76 (Period II), followed by a 4 week Follow up period.

Clinic visits were scheduled for Weeks 0, 2, 4, 8, 12, 24, 30, 32, 34, 42, 54, 66, 76, and

80. The patient or carer was allowed to administer interim doses of study drug at home every other week (eow) between clinic visits.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 645
• Est. completion date: January 18, 2018
• Est. primary completion date: January 18, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patient has completed the Week 24 visit procedures of Study FKB327-002 (NCT02260791) and are continuing with methotrexate

2. In the investigator's opinion, the patient showed a clinical response to treatment during Study FKB327-002 (NCT02260791)

Exclusion Criteria:

1. Patient has evidence of a serious adverse event (SAE) ongoing from Study FKB327-002

2. Patient has presence of active and/or untreated latent tuberculosis (TB)

Other Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid

Intervention

Drug:
• FKB327
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.
• Humira®
Solution of Humira® for subcutaneous injection administered in a dose of 40 mg every 2 weeks for 28 weeks. Patients may then receive FKB327 40 mg every other week by subcutaneous injection from week 30 to week 76.

Locations

Country	Name	City	State
Canada	Research Site	St. Catherines	Ontario
Canada	Research Site	Trois-Rivieres	Quebec
Chile	Research Site	Osorno
Chile	Research Site	Puerto Varas
Chile	Research Site G	Santiago
Chile	Research Site M	Santiago
Chile	Research Site	Temuco
Czechia	Research Site	Brno
Czechia	Research Site	Hlucin
Czechia	Research Site	Prague
Czechia	Research Site U	Prague
Czechia	Research Site	Uherske Hradiste
Czechia	Research Site	Zlin
Germany	Research Site	Aachen
Germany	Research Site	Berlin
Germany	Research Site	Hamburg
Germany	Research Site	Munich
Germany	Research Site	Ratingen
Peru	Research Site B	Arequipa
Peru	Research Site M	Arequipa
Peru	Research Site CA	Lima
Peru	Research Site CH	Lima
Peru	Research Site PA	Lima
Peru	Research Site S	Lima
Poland	Research Site D	Bialystok
Poland	Research Site R	Bialystok
Poland	Research Site	Gdynia
Poland	Research Site	Katowice
Poland	Research Site KL	Krakow
Poland	Research Site KR	Krakow
Poland	Research Site	Lublin
Poland	Research Site P	Poznan
Poland	Research Site RH	Poznan
Poland	Research Site	Torun
Romania	Research Site	Braila
Romania	Research Site	Brasov
Romania	Research Site C	Bucharest
Romania	Research Site R	Bucharest
Romania	Research Site T	Bucharest
Romania	Research Site	Galati
Romania	Research Site	Oradea	Bihor
Romania	Research Site	Sfantu Gheorghe	Covasna
Russian Federation	Research Site	Kazan	Tatarstan Republic
Russian Federation	Research Site D	Moscow
Russian Federation	Research Site SM	Moscow
Russian Federation	Research Site ST	Moscow
Russian Federation	Research Site	Nizhny Novgorod
Russian Federation	Research Site	Penza
Russian Federation	Research Site	Perm
Russian Federation	Research Site	Petrozavodsk	Karelia Republic
Russian Federation	Research Site	Ryazan
Russian Federation	Research Site B	Saint-Petersburg
Russian Federation	Research Site Z	Saint-Petersburg
Russian Federation	Research Site	Saratov
Russian Federation	Research Site	Smolensk
Russian Federation	Research Site	Ufa	Bashkortostan Republic
Russian Federation	Research Site	Vladimir
Russian Federation	Research Site E	Yaroslavl
Russian Federation	Research Site S	Yaroslavl
Spain	Research Site G	Barcelona
Spain	Research Site	Bilbao	Vizcaya
Spain	Research Site	Malaga
Spain	Research Site	Santiago de Compostela	La Coruna
Ukraine	Research Site	Chernivtsi
Ukraine	Research Site	Ivano-Frankivsk
Ukraine	Research Site A	Kyiv
Ukraine	Research Site B	Kyiv
Ukraine	Research Site P	Kyiv
Ukraine	Research Site	Lutsk
Ukraine	Research Site C	Lviv
Ukraine	Research Site N	Lviv
Ukraine	Research Site	Poltava
Ukraine	Research Site	Ternopil
Ukraine	Research Site	Uzhgorod
Ukraine	Research Site G	Vinnytsia
Ukraine	Research Site Sh	Vinnytsia
Ukraine	Research Site St	Vinnytsia
United States	Research Site	Amarillo	Texas
United States	Research Site	Austin	Texas
United States	Research Site	Boca Raton	Florida
United States	Research Site	Brandon	Florida
United States	Research Site	Duncansville	Pennsylvania
United States	Research Site	Durham	North Carolina
United States	Research Site	Jacksonville	Florida
United States	Research Site	Lansing	Michigan
United States	Research Site	Mesquite	Texas
United States	Research Site	Miami	Florida
United States	Research Site	Middleburg Heights	Ohio
United States	Research Site	Palm Desert	California
United States	Research Site	Peoria	Arizona
United States	Research Site	Sarasota	Florida
United States	Research Site	Shreveport	Louisiana

Sponsors (1)

Lead Sponsor	Collaborator
Fujifilm Kyowa Kirin Biologics Co., Ltd.

Countries where clinical trial is conducted

United States,  Canada,  Chile,  Czechia,  Germany,  Peru,  Poland,  Romania,  Russian Federation,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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 (%).	From Week 0 to Week 80
Other	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.	From Week 0 to Week 80
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.	Period I: from Week 0 up until Week 30;
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.	Period II: from Week 30 up to Week 80
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.	Period I: from Week 0 up until Week 30
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.	Period II: from Week 30 up to Week 80
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.	From Week 0 to Week 80
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.	From Week 0 to Week 80
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.	From Week 0 to Week 80
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).	From Week 0 to Week 80
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.	From Week 0 to Week 80
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).	From Week 0 of FKB327-002 to Week 80
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%	From Week 0 to Week 80
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%	From Week 0 to Week 80
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%	From Week 0 to Week 80