A Dose Response Study of E6011 in Participants With Rheumatoid Arthritis Inadequately Responding to Methotrexate

Eisai

Status and phase: Completed; Phase 2

Conditions: Rheumatoid Arthritis

Treatments: Drug: Placebo; Drug: E6011

Study type: Interventional

Funder types: Industry

Identifiers

NCT02960438

E6011-J081-201

Details and patient eligibility

About

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

Enrollment: 273 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

• Aged greater than or equal to (>=) 18 and less than (<)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 methotrexate (MTX) treatment at 6 to 16 milligram (mg)/week for >=12 weeks before screening and 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 MTX at 6 to 16 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
• Erosions at >=3 sites in radiographic image in the Screening Phase, or those with erosions at >=1 site and either positive for rheumatoid factor (RF) or anti-cyclic citrullinated peptide (CCP) antibody 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 (example, 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 (example, 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®TB Gold Test or T-SPOT®.TB 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 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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273 participants in 4 patient groups, including a placebo group

E6011 100 milligrams (mg)

Experimental group

Description:

In the Treatment Phase, E6011 100 mg will be subcutaneously administered at Weeks 0, 1, and 2, and then every 2 weeks up to Week 22. In the Extension Phase, E6011 200 mg will be subcutaneously administered every 2 weeks until Week 102.

Treatment:

Drug: E6011

E6011 200 mg

Experimental group

Description:

In the Treatment Phase, E6011 200 mg will be subcutaneously administered at Weeks 0, 1, and 2, and then every 2 weeks up to Week 22. In the Extension Phase, E6011 200 mg will be subcutaneously administered every 2 weeks until Week 102.

Treatment:

Drug: E6011

E6011 400 mg

Experimental group

Description:

In the Treatment Phase, E6011 400 mg will be subcutaneously administered at Weeks 0, 1, 2, 4, 6, 8, and 10, and then E6011 200 mg will be subcutaneously administered every 2 weeks up to Week 22. In the Extension Phase, E6011 200 mg will be subcutaneously administered every 2 weeks until Week 102.

Treatment:

Drug: E6011

Placebo

Placebo Comparator group

Description:

In the Treatment Phase, placebo will be subcutaneously administered at Weeks 0, 1, and 2, and then every 2 weeks up to Week 22. In the Extension Phase, E6011 200 mg will be subcutaneously administered every 2 weeks until Week 102.

Treatment:

Drug: Placebo