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Trial record 2 of 2 for:    FKB327

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.

Brief 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.

Condition or disease Intervention/treatment Phase
Arthritis, Rheumatoid Drug: FKB327 Drug: Humira® Phase 3

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 645 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 10, 2015
Actual Primary Completion Date : January 18, 2018
Actual Study Completion Date : January 18, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Adalimumab

Arm Intervention/treatment
Experimental: FKB327
Patients will receive the drug 40 mg every other week by subcutaneous injection. The treatment period may continue for 76 weeks.
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.
Other Name: adalimumab biosimilar

Active Comparator: Humira®
Patients will receive the drug 40 mg every other week by subcutaneous injection. The treatment period may continue for 76 weeks.
Drug: 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.
Other Name: adalimumab




Primary Outcome Measures :
  1. Number of Patients With Adverse Events as a Measure of Safety Per Treatment Group in Period I [ Time Frame: Period I: from Week 0 up until Week 30; ]

    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.


  2. Number of Patients With Adverse Events as a Measure of Safety in Period II - Single Treatment Period [ Time Frame: Period II: from Week 30 up to Week 80 ]
    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.

  3. Number of Patients With Serious Adverse Events as a Measure of Safety Per Treatment Group in Period I [ Time Frame: Period I: from Week 0 up until Week 30 ]

    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.


  4. Number of Patients With Serious Adverse Events as a Measure of Safety in Period II - Single Treatment Period [ Time Frame: Period II: from Week 30 up to Week 80 ]

    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.


  5. Changes in Vital Signs as a Measure of Safety - Systolic Blood Pressure [ Time Frame: From Week 0 to Week 80 ]

    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.


  6. Changes in Vital Signs as a Measure of Safety - Diastolic Blood Pressure [ Time Frame: From Week 0 to Week 80 ]

    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.


  7. Changes in Vital Signs as a Measure of Safety - Pulse Rate [ Time Frame: From Week 0 to Week 80 ]

    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.


  8. Changes in Vital Signs as a Measure of Safety - Temperature Measurements [ Time Frame: From Week 0 to Week 80 ]

    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).


  9. Summary of Most Common Clinical Significant Laboratory Parameters Reported as Adverse Events (Reported by ≥1% of the Patients) [ Time Frame: From Week 0 to Week 80 ]
    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.


Secondary Outcome Measures :
  1. Changes in Disease Activity Score 28 Based on C Reactive Protein (DAS28 CRP) Score Compared to Baseline as a Measure of Efficacy [ Time Frame: From Week 0 of FKB327-002 to Week 80 ]

    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).


  2. American College of Rheumatology 20 (ACR20) Response Rates From Baseline as a Measure of Efficacy [ Time Frame: From Week 0 to Week 80 ]

    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%

  3. American College of Rheumatology 50 (ACR50) Response Rates From Baseline as a Measure of Efficacy [ Time Frame: From Week 0 to Week 80 ]

    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%

  4. American College of Rheumatology 70 (ACR70) Response Rates From Baseline as a Measure of Efficacy [ Time Frame: From Week 0 to Week 80 ]

    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%


Other Outcome Measures:
  1. Proportion of Patients Developing Anti-drug Antibodies (ADAs) [ Time Frame: From Week 0 to Week 80 ]

    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 (%).


  2. Trough Adalimumab Concentration [ Time Frame: From Week 0 to Week 80 ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02405780


Locations
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Sponsors and Collaborators
Fujifilm Kyowa Kirin Biologics Co., Ltd.
Investigators
Layout table for investigator information
Principal Investigator: Josephine Glover, MD Coephycient Pharmaceutical Consultancy
  Study Documents (Full-Text)

Documents provided by Fujifilm Kyowa Kirin Biologics Co., Ltd.:
Study Protocol  [PDF] April 15, 2016
Statistical Analysis Plan  [PDF] July 10, 2018


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Fujifilm Kyowa Kirin Biologics Co., Ltd.
ClinicalTrials.gov Identifier: NCT02405780    
Other Study ID Numbers: FKB327-003
First Posted: April 1, 2015    Key Record Dates
Results First Posted: March 26, 2019
Last Update Posted: March 26, 2019
Last Verified: March 2019
Keywords provided by Fujifilm Kyowa Kirin Biologics Co., Ltd.:
Rheumatoid
Arthritis
Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Adalimumab
Anti-Inflammatory Agents
Antirheumatic Agents