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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Arthritis, Rheumatoid

Intervention / Treatment
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* Drug: FKB327
* Drug: Humira®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient has completed the Week 24 visit procedures of Study FKB327-002 (NCT02260791) and are continuing with methotrexate In the investigator's opinion, the patient showed a clinical response to treatment during Study FKB327-002 (NCT02260791) Exclusion Criteria: Patient has evidence of a serious adverse event (SAE) ongoing from Study FKB327-002 Patient has presence of active and/or untreated latent tuberculosis (TB) Other Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FKB327<br>Patients will receive the drug 40 mg every other week by subcutaneous injection. The treatment period may continue for 76 weeks. | Drug: FKB327<br>* 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.<br>* Other names: adalimumab biosimilar;|
| Active Comparator: Humira®<br>Patients will receive the drug 40 mg every other week by subcutaneous injection. The treatment period may continue for 76 weeks. | Drug: Humira®<br>* 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.<br>* Other names: adalimumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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. | Period II: from Week 30 up to Week 80 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 Outcome Measures

| Outcome Measure | 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). | From Week 0 of FKB327-002 to Week 80 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid, Arthritis