A Phase 2 Study of E6011 in Subjects With Rheumatoid Arthritis Inadequately Responding to Biologics
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: E6011; Placebo
Intervention description: subcutaneous administration; subcutaneous administration
Intervention MeSH terms: Quetmolimab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 66.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: E6011; rheumatoid arthritis

Summary:

      This study is a multicenter, randomized, double-blind, placebo-controlled, parallel-group
      comparison study in rheumatoid arthritis participants inadequately responding to biologics.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Aged ≥18 and <75 years old at the time of informed consent

          -  Diagnosed with rheumatoid arthritis (RA) under the 1987 American College of
             Rheumatology (ACR) or 2010 ACR/European League Against Rheumatism (EULAR) criteria ≥12
             weeks before informed consent

          -  Received biologics treatment under approved dosage and administration for ≥12 weeks
             but discontinued it before screening because of inadequate response

          -  History of biologics treatment should be limited to 2 agents among adalimumab,
             infliximab, golimumab, certolizumab pegol, etanercept, tocilizumab, and abatacept
             (including biosimilars)

          -  Presented ≥6 tender joints (out of 68 joints) and ≥6 swollen joints (out of 66 joints)
             in the Screening and Observation Phases

          -  Can continue stable dose regimen of methotrexate at 6 to 16 milligrams (mg)/week from
             4 weeks before starting the study treatment until completion of the Extension Phase
             (or until study discontinuation)

          -  C-reactive protein (CRP) level ≥0.6 mg/deciliter (dL) or erythrocyte sedimentation
             rate (ESR) ≥28 millimeters per hour (mm/hr) in the Screening Phase

          -  Weighs ≥30 kilograms (kg) and ≤100 kg in the Screening Phase

          -  Has voluntarily consented, in writing, to participate in this study. If a participant
             is below the age of 20, also consented, in writing by a legally acceptable
             representative

          -  Has been thoroughly briefed on the conditions for participation in the study, is able
             to understand, and is willing and able to comply with all aspects of the protocol

        Exclusion Criteria:

          -  Any history or complication of inflammatory arthritic disorder other than RA or
             Sjogren's syndrome

          -  Meets the ACR 1991 Revised Criteria for the Classification of Global Functional Status
             in RA Class IV in the Screening Phase

          -  Received immunoglobulin preparations or blood products within 24 weeks before starting
             the study treatment

          -  Received a live vaccine within 12 weeks before starting the study treatment, or is
             planning to receive

          -  Evidence of clinically significant disease (e.g., cardiac, respiratory,
             gastrointestinal, or renal disease) that could affect the participant's safety or
             interfere with the study assessments in the opinion of the investigator or
             subinvestigator

          -  Complication of uncontrolled disorders such as acute cardiac infarction, unstable
             angina, brain infarct, or symptomatic intracerebral hemorrhage

          -  History of severe allergy (shock or anaphylactoid symptoms)

          -  History or current clinical condition of malignant tumor, lymphoma, leukemia, or
             lymphoproliferative disease, except for skin carcinoma (epithelial carcinoma or basal
             cell carcinoma) and cervix carcinoma which has completely excised and without
             metastasis or recurrence for more than 5 years before informed consent

          -  Immunodeficiency or history of human immunodeficiency virus (HIV) infection

          -  Infection requiring hospitalization or intravenous administration of antibiotics or
             disease requiring administration of antivirus drugs (e.g., herpes zoster) within 4
             weeks before starting the study treatment

          -  History of tuberculosis or current complication of active tuberculosis

          -  History of clinically important vasculitis

          -  Tested positive for any of the following in the Screening Phase: HIV, hepatitis B
             virus surface antigen (HBs antigen), hepatitis B virus surface antibody (HBs
             antibody), hepatitis B virus core antibody (HBc antibody), hepatitis B virus
             deoxyribonucleic acid (HBV DNA), hepatitis C virus antibody (HCV antibody), human
             T-lymphotrophic virus Type I antibody (HTLV-1 antibody), or syphilis

          -  Positive in tuberculosis test (QuantiFERON Tuberculosis Gold Test or T-SPOT
             Tuberculosis Test) in the Screening Phase

          -  Findings indicating a history of tuberculosis on chest x-ray in the Screening Phase

          -  Neurological findings such as paralysis, visual impairment, or language disorder in
             the Screening Phase

          -  Demonstrated prolonged QTcF (Fridericia's Correction Formula) interval (>450
             milliseconds [ms]) in repeated electrocardiogram examinations

          -  Females of childbearing potential who have a positive pregnancy test in the Screening
             or Observation Phase or are breastfeeding

          -  Females of childbearing potential who:

               -  Had unprotected sexual intercourse within 30 days before study entry and who do
                  not agree to use a highly effective method of contraception (e.g., total
                  abstinence, an intrauterine device, a double-barrier method [such as condom plus
                  diaphragm with spermicide], a contraceptive implant, an oral contraceptive, or
                  have a vasectomized partner with confirmed azoospermia) throughout the entire
                  study period or for 28 days after study drug discontinuation

               -  Are currently abstinent, and do not agree to use a double-barrier method (as
                  described above) or refrain from being sexually active during the study period or
                  for 28 days after study drug discontinuation

               -  Are using hormonal contraceptives but are not on a stable dose of the same
                  hormonal contraceptive product for at least 4 weeks before dosing and who do not
                  agree to use the same contraceptive during the study or for 28 days after study
                  drug discontinuation.

        (NOTE: All females will be considered to be of childbearing potential unless they are
        postmenopausal [amenorrheic for at least 12 consecutive months, in the appropriate age
        group, and without other known or suspected cause] or have been sterilized surgically
        [i.e., bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with
        surgery at least 1 month before dosing]).

          -  Males who have not had a successful vasectomy (confirmed azoospermia) or they and
             their female partners do not meet the criteria above (i.e., not of childbearing
             potential or practicing highly effective contraception throughout the study period or
             for 28 days after study drug discontinuation). No sperm donation is allowed during the
             study period or for 28 days after study drug discontinuation.

          -  Scheduled for surgery during the study

          -  Currently enrolled in another clinical study or used any investigational drug or
             device within 28 days (or 5× the half-life, whichever is longer) before informed
             consent

          -  Has been treated with E6011 or any biologics for use in RA that has not been approved

          -  Use of a psychotropic agent as recreational purpose other than therapeutic purpose

          -  Any history of a medical condition or a concomitant medical condition that in the
             opinion of the investigator or subinvestigator would compromise the participant's
             ability to safely complete the study