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

NCT02960490 | Completed Phase 2 Results

• 1 other identifier: E6011-J081-202
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 45

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

Keywords

E6011; rheumatoid arthritis

Outcome Measures

Primary Outcomes (1)

• Core Treatment Phase: Percentage of Participants Who Achieved an American College of Rheumatology (ACR) 20 Response at Week 12 Based on Non-responder Imputation (NRI)

  The ACR20 response was defined as if the following 3 criteria (ACR components) were met: Greater than or equal to (\>=) 20 percent (%) reduction from baseline in the tender joint count (TJC) in 68 joints (TJC68); \>=20% reduction from baseline in the swollen joint count (SJC) in 66 joints (SJC66); \>=20% reduction from baseline in at least 3 of the following 5 assessments: Physician's Global Assessment of Disease Activity (visual analog scale \[VAS\]), Participant's Global Assessment of Disease Activity (VAS), Participant's Assessment of Pain (VAS), Health Assessment Questionnaire disability index (HAQ-DI), and C-reactive protein (CRP).

  Week 12

Secondary Outcomes (20)

• Percentage of Participants Who Achieved an ACR20 Response at Weeks 2, 4, 8, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68 and 72 Based on NRI

  Core Treatment Phase: Weeks 2, 4, 8, 16, 20, 24; Extension Phase: Weeks 2, 4, 8, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68 and 72

• Percentage of Participants Who Achieved an ACR50 Response at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68 and 72 Based on NRI

  Core Treatment Phase: Weeks 2, 4, 8, 12, 16, 20 and 24; Extension Phase: Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68 and 72

• Percentage of Participants Who Achieved an ACR70 Response at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68 and 72 Based on NRI

  Core Treatment Phase: Weeks 2, 4, 8, 12, 16, 20 and 24; Extension Phase: Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68 and 72

• Change From Baseline in Tender Joint Counts (TJC) at Each Visit Based on Last Observation Carried Forward (LOCF)

  Core Treatment Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20 and 24; Extension Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68 and 72

• Change From Baseline in Swollen Joint Counts (SJC) at Each Visit Based on LOCF

  Core Treatment Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20 and 24; Extension Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68 and 72

Study Arms (4)

E6011 400 mg/E6011 200 mg

EXPERIMENTAL

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.

Drug: E6011

E6011 400 mg/E6011 400 mg

EXPERIMENTAL

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.

Drug: E6011

Placebo/E6011 200 mg

EXPERIMENTAL

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.

Drug: E6011; Drug: Placebo

Placebo/E6011 400 mg

EXPERIMENTAL

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.

Drug: E6011; Drug: Placebo

Interventions

E6011 DRUG

subcutaneous administration

E6011 400 mg/E6011 200 mg; E6011 400 mg/E6011 400 mg; Placebo/E6011 200 mg; Placebo/E6011 400 mg

Placebo DRUG

subcutaneous administration

Placebo/E6011 200 mg; Placebo/E6011 400 mg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eisai Co., Ltd.: lead

Study Sites (45)

Eisai Trial Site #1

Yotsukaidō, Chiba, Japan

Location

Eisai Trial Site #1

Matsuyama, Ehime, Japan

Location

Eisai Trial Site #1

Kitakyushu, Fukuoka, Japan

Location

Eisai Trial Site #1

Takasaki, Gunma, Japan

Location

Eisai Trial Site #2

Takasaki, Gunma, Japan

Location

Eisai Trial Site #1

Asahikawa, Hokkaido, Japan

Location

Eisai Trial Site #1

Sapporo, Hokkaido, Japan

Location

Eisai Trial Site #2

Sapporo, Hokkaido, Japan

Location

Eisai Trial Site #3

Sapporo, Hokkaido, Japan

Location

Eisai Trial Site #1

Katō, Hyōgo, Japan

Location

Eisai Trial Site #1

Ono, Hyōgo, Japan

Location

Eisai Trial Site #1

Tsukuba, Ibaraki, Japan

Location

Eisai Trial Site #1

Sagamihara, Kanagawa, Japan

Location

Eisai Trial Site #1

Yokohama, Kanagawa, Japan

Location

Eisai Trial Site #1

Sasebo, Nagasaki, Japan

Location

Eisai Trial Site #1

Tomigusuku, Okinawa, Japan

Location

Eisai Trial Site #1

Kawachi-Nagano, Osaka, Japan

Location

Eisai Trial Site #1

Kawagoe, Saitama, Japan

Location

Eisai Trial Site #1

Kawaguchi, Saitama, Japan

Location

Eisai Trial Site #1

Tokorozawa, Saitama, Japan

Location

Eisai Trial Site #1

Hamamatsu, Shizuoka, Japan

Location

Eisai Trial Site #1

Shimotsuke, Tochigi, Japan

Location

Eisai Trial Site #1

Chūō, Tokyo, Japan

Location

Eisai Trial Site #1

Fuchū, Tokyo, Japan

Location

Eisai Trial Site #1

Meguro-ku, Tokyo, Japan

Location

Eisai Trial Site #1

Ōta-ku, Tokyo, Japan

Location

Eisai Trial Site #1

Setagaya City, Tokyo, Japan

Location

Eisai Trial Site #1

Shinjuku, Tokyo, Japan

Location

Eisai Trial Site #2

Shinjuku, Tokyo, Japan

Location

Eisai Trial Site #1

Takaoka, Toyama, Japan

Location

Eisai Trial Site #1

Chiba, Japan

Location

Eisai Trial Site #1

Fukui, Japan

Location

Eisai Trial Site #2

Fukuoka, Japan

Location

Eisai Trial Site #3

Fukuoka, Japan

Location

Eisai Trial Site #4

Fukuoka, Japan

Location

Eisai Trial Site #5

Fukuoka, Japan

Location

Eisai Trial Site #1

Hiroshima, Japan

Location

Eisai Trial Site #1

Kagoshima, Japan

Location

Eisai Trial Site #1

Kochi, Japan

Location

Eisai Trial Site #1

Kyoto, Japan

Location

Eisai Trial Site #1

Nagasaki, Japan

Location

Eisai Trial Site #2

Nagasaki, Japan

Location

Eisai Trial Site #3

Nagasaki, Japan

Location

Eisai Trial Site #1

Ōita, Japan

Location

Eisai Trial Site #1

Toyama, Japan

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

quetmolimab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Inquiry Service.
• Organization: Eisai Co., Ltd.

eisai-chiken_hotline@hhc.eisai.co.jp

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2016
• First Posted: November 9, 2016
• Study Start: November 26, 2016
• Primary Completion: May 16, 2018
• Study Completion: November 25, 2019
• Last Updated: August 23, 2021
• Results First Posted: August 23, 2021

Record last verified: 2019-12

Locations

JP (45)