Study to assess the efficacy and safety of FKB327 compared with Humira®, when each is administered in combination with Methotrexate in patients with Rheumatoid Arthritis.

Phase 1

Conditions: Rheumatoid Arthritis
MedDRA version: 17.1Level: PTClassification code 10039073Term: Rheumatoid arthritisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Registration Number: EUCTR2014-000109-11-ES

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

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 600

Inclusion Criteria

_ Men or women aged ? 18 years.
_ RA, diagnosed to revised American College of Rheumatology (ACR) criteria (2010 version) at least 3 months prior to Screening.
_ Active RA, as confirmed by tender and swollen joint counts ?6 out of 68/66, respectively, at Screening and at Baseline.
_ C-reactive protein (CRP) level ?1.0 mg/dL at Screening.
_ Taking MTX (oral or parenteral) for at least 3 months prior to Screening and at a stable dose of between 10 and 25 mg/week for at least 8 weeks, with concomitant folic/folinic acid of at least 5 mg/week. Patients can start treatment with folic acid if not already receiving it.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 510
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 90

Exclusion Criteria

Patients will be excluded from the study if any of the following exclusion criteria are met (list not comprehensive):
_ Prior treatment with adalimumab.
_ Prior treatment with 2 or more biological disease modifying anti-rheumatic drugs (DMARDs) or protein kinase inhibitors for RA.
_ Prior treatment with tumour necrosis factor (TNF) inhibitors with lack of efficacy.
_ Prior treatment with cyclophosphamide or other cytotoxic agents.
_ Treatment with an investigational agent within 12 weeks or 5 half-lives of the drug.
_ Immunisation with a live or attenuated vaccine within 4 weeks prior to study drug dosing.
_ Intra-articular or parenteral steroids within 28 days prior to Screening.
_ Treatment with any DMARDs, other than MTX.
_ History of relevant allergy/hypersensitivity to monoclonal antibodies or any of the excipients of FKB327 or Humira.
_ Presence of autoimmune disease or joint disease other than RA.
_ ACR functional Class IV.
_ Major surgery within 8 weeks prior to Screening or planned to take place during the study period.
_ Presence of chronic or acute infection at Screening including positive result for human immunodeficiency virus (HIV) 1 or 2, hepatitis B (HBV), hepatitis C (HCV), and active tuberculosis (TB) or untreated latent TB.
_ Acute infection requiring parenteral antibiotics within 4 weeks of study dosing.
_ Presence of serious, uncontrolled disease of another body system including cardiovascular, neurological, pulmonary, renal and hepatic disease.
_ Presence of New York Heart Association (NYHA) Class III/IV heart failure.
_ Presence of any uncontrolled disease for which steroid treatment is regularly required for flares.
_ Presence of any malignancy or history of malignancy in the 5 years.
_ Patients with aspartate transaminase or alanine transaminase >1.5 × ULN, haemoglobin <8 g/dL, absolute neutrophil count<1500/?L, platelets <100,000/?L, and/or creatinine >1.5 × ULN.
_ Patients with demyelinating diseases.
_ Pregnant or breastfeeding women.
_ Patients with any condition or circumstances, which, in the opinion of the Investigator, make them unlikely or unable to comply with study procedures and requirements.
_ Body weight >120 kg.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of this study is to assess the efficacy of FKB327 compared with Humira®, when each is administered in combination with methotrexate.;Secondary Objective: The secondary objectives of this study are as follows:<br>_ To compare the safety profiles of FKB327 and Humira, each in combination with methotrexate treatment.<br>_ To assess the efficacy profiles of FKB327 and Humira over time, including initial onset of effect.<br>_ To compare the proportions of patients on FKB327 and Humira, who develop anti drug antibodies (ADAs) and to summarise the distribution of the level of ADA activity between patients on FKB327 and Humira.<br>_ To compare the steady state pharmacokinetics of FKB327 and Humira administered by multiple dosing in patients with RA receiving concomitant treatment with methotrexate.;Primary end point(s): The primary efficacy endpoint is the ACR20 response rate.;Timepoint(s) of evaluation of this end point: The ACR20 response rate is evaluated at Week 24.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): The key secondary efficacy endpoint is as follows:<br>_ DAS28-CRP score.<br><br>Other secondary efficacy endpoints are as follows:<br>_ ACR20, ACR50 and ACR70 response rates.<br>_ Values of the individual ACR core set variables (swollen joint count, tender joint count, CRP, patient?s assessment of disease activity, physician?s assessment of disease activity, patient?s assessment of pain, Health Assessment Questionnaire Disability Index [HAQ DI]) .<br>_ DAS28-RP score and change in DAS28-CRP score .<br>_ DAS28 score based on erythrocyte sedimentation rate (DAS28-ESR).;Timepoint(s) of evaluation of this end point: _ DAS28-CRP score is evaluated at Week 24.<br>_ ACR20, ACR50 and ACR70 response rates are evaluated over time.<br>_ Values of the individual ACR core set variables are evaluated over time.<br>_ DAS28-CRP score and change in DAS28-CRP score are evaluated over time.<br>_ DAS28-ESR score is evaluated at Weeks 12 and 24.

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