A Study of Certolizumab Pegol as Additional Therapy in Chinese Patients With Active Rheumatoid Arthritis
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Certolizumab Pegol; Methotrexate; Placebo
Intervention description: Active substance: Certolizumab Pegol
Pharmaceutical Form: Prefilled syringes
Concentration: 200 mg/ml
Route of administration: Subcutaneous injection; Active substance: Methotrexate
Pharmaceutical form: Tablet
Concentration: Maximum dose 10 mg per week
Route of administration: Oral; Active substance: Placebo
Pharmaceutical form: Prefilled syringes
Concentration: 0.9 % saline
Route of Administration: Subcutaneous injection
Intervention MeSH terms: Certolizumab Pegol; Methotrexate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 430.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Rheumatoid Arthritis; TNFα antagonist; Certolizumab Pegol; Chinese patients

Summary:

      This study will evaluate the safety & efficacy of Certolizumab Pegol (CZP) as additional
      medication to Methotrexate (MTX) in Chinese subjects with Rheumatoid Arthritis. 400 patients
      will be randomized to receive either CZP + MTX or placebo + MTX. Anticipated time in the
      study is about 32 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          -  An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved
             written Informed Consent form (ICF) is signed and dated by the subject or by the legal
             representative

          -  Subject is considered reliable and capable of adhering to the protocol (eg, able to
             understand and complete questionnaires), visit schedule, and medication intake
             according to the judgment of the Investigator

          -  Subject is male or female, and at least 18 years of age at the Screening Visit

          -  Subjects must have a diagnosis of adult onset Rheumatoid Arthritis RA of at least 6
             months duration as defined by the 1987 American College of Rheumatology (ACR)
             classification criteria (Arnett et al, 1988).

          -  Subjects must have active RA disease as defined by:

               -  ≥6 tender joints at Screening and Baseline

               -  ≥6 swollen joints at Screening and Baseline

               -  Fulfilling 1 of the following 2 criteria during the Screening Period:

               -  European League Against Rheumatism (ESR) (Westergren) ≥30 mm/hour, or

               -  C-reactive protein (CRP) >15 mg/L

          -  Subjects must have a normal chest x ray within 3 months prior to the Baseline Visit

          -  Female subjects with childbearing potential should have a negative pregnancy test at
             Screening and at Baseline and should have a medically accepted method of contraception
             used during the entire duration of the study and for 10 weeks after the last dose of
             Certolizumab Pegol (CZP).

          -  Male subjects must agree to ensure they use adequate contraception during the study
             and for at least 10 weeks after the subject receives their last dose of study
             medication

          -  Subjects must have received treatment with Methotrexate (MTX) (with or without folic
             acid) for at least 3 months prior to the Baseline Visit. The dose and route of
             administration of MTX must have been stable for at least 2 months prior to the
             Baseline Visit. The minimum stable dose of MTX allowed is 10 mg weekly

        Exclusion Criteria:

        Rheumatoid Arthritis disease-related exclusions:

          -  Subjects have a diagnosis of any other inflammatory arthritis (eg, psoriatic arthritis
             or ankylosing spondylitis)

          -  Subjects have a secondary, noninflammatory type of arthritis (eg, Osteoarthritis or
             Fibromyalgia) that in the Investigator's opinion is symptomatic enough to interfere
             with evaluation of the effect of study medication on the subject's primary diagnosis
             of Rheumatoid Arthritis (RA)

          -  Subjects have a history of an infected joint prosthesis at any time with that
             prosthesis still in situ

          -  Subjects have >3 arthroplasties due to RA and/or Steinbrocker IV functional capacity

        Concomitant medication exclusions:

          -  Subjects must be free of prohibited medication, Analgesics (including Paracetamol and
             Acetominophen), NSAIDs /COX-2 Inhibitors, Oral corticosteroids, DMARDs, etc. as
             detailed in protocol Previous clinical studies and previous biological therapy
             exclusions

          -  Subjects have previously participated in this study or subject has previously been
             assigned to treatment in a study of the medication under investigation in this study

          -  Subjects have participated in another study of an investigational medicinal product
             (or a medical device) within the previous 3 months or are currently participating in
             another study of an investigational medicinal product (or a medical device)

          -  Subjects have received any experimental nonbiological therapy, within or outside a
             clinical study in the 3 months or within 5 half lives (whichever is longer) prior to
             Baseline Visit

          -  Subjects have received any biological therapy for RA within 3 months or within 5 half
             lives (whichever is longer) prior to Baseline Visit, except for Etanercept and
             Anakinra where only a 1 month washout prior to the Baseline Visit is necessary

          -  Subjects have received Rituximab or Tocilizumab

          -  Subjects have received Yunke (technetium-99 conjugated with methylene diphosphonate)
             other than for diagnostic purpose within 5 years prior to Baseline

          -  Subjects have received previous treatment with a biological therapy for RA that
             resulted in a severe hypersensitivity reaction or an anaphylactic reaction

          -  Subjects who failed to respond to previous treatment with a Tumor Necrosis Factor
             (TNF) blocking drug are excluded. Subjects who initially responded to a maximum of 2
             TNF blocking agents but who later discontinued the agent(s) due to loss of efficacy or
             other reasons may be included

        Medical history exclusions:

          -  Female subjects who are breast feeding, pregnant, or plan to become pregnant during
             the study or for 3 months following last dose of study medication

          -  Subjects with a history of chronic infection, recent serious or life threatening
             infection (within 6 months, including herpes zoster), or a current sign or symptom
             that may indicate an infection (eg, fever, cough)

          -  Subjects with a history or active systemic/respiratory infection due to fungal,
             parasitic, or mycotic pathogens including but not limited to histoplasmosis,
             coccidiosis, paracoccidiosis, pneumocystis, blastomyces, aspergillus, and
             nontuberculous mycobacteria (NTMB)

          -  Radiographic evidence suggestive of any of these infections is sufficient grounds for
             exclusion

          -  Subjects with known Tuberculosis (TB) infection, at high risk of acquiring TB
             infection, or Latent Tuberculosis (LTB) infection are excluded

          -  Subjects at a high risk of infection (eg, leg ulcers, indwelling urinary catheter,
             persistent or recurrent chest infections, and subjects that are permanently bedridden
             or wheelchair bound)

          -  Subjects with a positive Hepatitis B surface antigen (HBsAg) test and/or Hepatitis C
             virus antibody (anti HCV) test result

          -  Subjects with positive human immunodeficiency virus (HIV) test

          -  Subjects receiving any live (includes attenuated) vaccination within 56 days prior to
             Baseline (eg, injectable influenza and pneumococcal vaccines are allowed, but nasal
             influenza vaccine is not)

          -  Subjects with a history of a lymphoproliferative disorder including lymphoma or signs
             and symptoms suggestive of lymphoproliferative disease at any time

          -  Subjects with an active malignancy of any type or a history of malignancy (other than
             carcinoma of the cervix or basal cell carcinoma successfully treated more than 5 years
             prior to Screening)

          -  Subjects with a history of blood dyscrasias, eg, leukemia or hemophilia where the
             blood constituents are abnormal or are present in abnormal quantity

          -  Subjects with class III or IV congestive heart failure New York Heart Association
             (NYHA) 1994

          -  Subjects with a history of, or suspected, demyelinating disease of the central nervous
             system (eg, multiple sclerosis or optic neuritis)

          -  Subjects with a current or recent history, as determined by the Investigator, of
             severe, progressive, and/or uncontrolled renal, hepatic, hematological, GI, endocrine,
             pulmonary, cardiac, neurological, or cerebral disease which would interfere with the
             subject's participation in the study. Abnormal laboratory parameters as detailed in
             protocol that require exclusion of a subject

          -  Subjects with a history of an adverse reaction to Polyethylene Glycol (PEG) or a
             protein based medicinal product or known hypersensitivity to any components of the
             study medication or comparative drugs as stated in this protocol