A Phase 2 Study of E6011 in Subjects With Rheumatoid Arthritis Inadequately Responding to Biologics

NCT ID: NCT02960490

Last Updated: 2021-08-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-26
• Study Completion Date: 2019-11-25

Brief Summary

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

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

E6011 400 mg/E6011 200 mg

In the Treatment Phase (24 weeks), participants will receive E6011 400 milligrams (mg) at Weeks 0, 1, and 2, and then every 2 weeks subsequently until Week 10, and will then receive E6011 200 mg every 2 weeks between Weeks 12 and 22 in a double-blind manner. Participants who complete evaluations at Week 24 of the Treatment Phase will enter the Extension Phase (conducted up to Week 104 from the start of the study treatment), in which they will receive open-label E6011 200 mg every 2 weeks until Week 102.

Group Type: EXPERIMENTAL

E6011

Intervention Type: DRUG

subcutaneous administration

E6011 400 mg/E6011 400 mg

In the Treatment Phase (24 weeks), participants will receive E6011 400 mg at Weeks 0, 1, and 2, and then every 2 weeks subsequently until Week 10, and will then receive E6011 400 mg every 2 weeks between Weeks 12 and 22 in a double-blind manner. Participants who complete evaluations at Week 24 of the Treatment Phase will enter the Extension Phase (conducted up to Week 104 from the start of the study treatment), in which they will receive open-label E6011 200 mg every 2 weeks until Week 102.

Group Type: EXPERIMENTAL

E6011

Intervention Type: DRUG

subcutaneous administration

Placebo/E6011 200 mg

In the Treatment Phase (24 weeks), participants will receive placebo at Weeks 0, 1, and 2, and then every 2 weeks subsequently until Week 10, and will then receive E6011 200 mg every 2 weeks between Weeks 12 and 22 in a double-blind manner. Participants who complete evaluations at Week 24 of the Treatment Phase will enter the Extension Phase (conducted up to Week 104 from the start of the study treatment), in which they will receive open-label E6011 200 mg every 2 weeks until Week 102.

Group Type: EXPERIMENTAL

E6011

Intervention Type: DRUG

subcutaneous administration

Placebo

Intervention Type: DRUG

subcutaneous administration

Placebo/E6011 400 mg

In the Treatment Phase (24 weeks), participants will receive placebo at Weeks 0, 1, and 2, and then every 2 weeks subsequently until Week 10, and will then receive E6011 400 mg every 2 weeks between Weeks 12 and 22 in a double-blind manner. Participants who complete evaluations at Week 24 of the Treatment Phase will enter the Extension Phase (conducted up to Week 104 from the start of the study treatment), in which they will receive open-label E6011 200 mg every 2 weeks until Week 102.

Group Type: EXPERIMENTAL

E6011

Intervention Type: DRUG

subcutaneous administration

Placebo

Intervention Type: DRUG

subcutaneous administration

Interventions

E6011

subcutaneous administration

Intervention Type: DRUG

Placebo

subcutaneous administration

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eisai Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Eisai Trial Site #1

Yotsukaidō, Chiba, Japan

Eisai Trial Site #1

Matsuyama, Ehime, Japan

Eisai Trial Site #1

Kitakyushu, Fukuoka, Japan

Eisai Trial Site #1

Takasaki, Gunma, Japan

Eisai Trial Site #2

Takasaki, Gunma, Japan

Eisai Trial Site #1

Asahikawa, Hokkaido, Japan

Eisai Trial Site #1

Sapporo, Hokkaido, Japan

Eisai Trial Site #2

Sapporo, Hokkaido, Japan

Eisai Trial Site #3

Sapporo, Hokkaido, Japan

Eisai Trial Site #1

Katō, Hyōgo, Japan

Eisai Trial Site #1

Ono, Hyōgo, Japan

Eisai Trial Site #1

Tsukuba, Ibaraki, Japan

Eisai Trial Site #1

Sagamihara, Kanagawa, Japan

Eisai Trial Site #1

Yokohama, Kanagawa, Japan

Eisai Trial Site #1

Sasebo, Nagasaki, Japan

Eisai Trial Site #1

Tomigusuku, Okinawa, Japan

Eisai Trial Site #1

Kawachi-Nagano, Osaka, Japan

Eisai Trial Site #1

Kawagoe, Saitama, Japan

Eisai Trial Site #1

Kawaguchi, Saitama, Japan

Eisai Trial Site #1

Tokorozawa, Saitama, Japan

Eisai Trial Site #1

Hamamatsu, Shizuoka, Japan

Eisai Trial Site #1

Shimotsuke, Tochigi, Japan

Eisai Trial Site #1

Chūō, Tokyo, Japan

Eisai Trial Site #1

Fuchū, Tokyo, Japan

Eisai Trial Site #1

Meguro-ku, Tokyo, Japan

Eisai Trial Site #1

Ōta-ku, Tokyo, Japan

Eisai Trial Site #1

Setagaya City, Tokyo, Japan

Eisai Trial Site #1

Shinjuku, Tokyo, Japan

Eisai Trial Site #2

Shinjuku, Tokyo, Japan

Eisai Trial Site #1

Takaoka, Toyama, Japan

Eisai Trial Site #1

Chiba, , Japan

Eisai Trial Site #1

Fukui, , Japan

Eisai Trial Site #2

Fukuoka, , Japan

Eisai Trial Site #3

Fukuoka, , Japan

Eisai Trial Site #4

Fukuoka, , Japan

Eisai Trial Site #5

Fukuoka, , Japan

Eisai Trial Site #1

Hiroshima, , Japan

Eisai Trial Site #1

Kagoshima, , Japan

Eisai Trial Site #1

Kochi, , Japan

Eisai Trial Site #1

Kyoto, , Japan

Eisai Trial Site #1

Nagasaki, , Japan

Eisai Trial Site #2

Nagasaki, , Japan

Eisai Trial Site #3

Nagasaki, , Japan

Eisai Trial Site #1

Ōita, , Japan

Eisai Trial Site #1

Toyama, , Japan

Countries

Japan

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan: Core and Entire Treatment Phase

View Document

Document Type: Statistical Analysis Plan: Extension Phase

View Document

Other Identifiers

E6011-J081-202

Identifier Type: -

Identifier Source: org_study_id