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

NCT02960438 | Completed Phase 2 Results

• 1 other identifier: E6011-J081-201
• Study Type: interventional
• Target: 273
• Locations: 1 country
• Sites: 90

Brief Summary

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

Conditions

Rheumatoid Arthritis

Keywords

E6011; rheumatoid arthritis

Outcome Measures

Primary Outcomes (1)

• Treatment Phase: Percentage of Participants Who Achieved an American College of Rheumatology 20 (ACR20) 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 (21)

• Treatment Phase: Percentage of Participants Who Achieved an ACR20 Response at Weeks 2, 4, 8, 16, 20 and 24 Based on NRI

  Weeks 2, 4, 8, 16, 20, and 24

• Treatment Phase: Percentage of Participants Who Achieved an ACR50 Response at Weeks 2, 4, 8, 16, 20 and 24 Based on NRI

  Weeks 2, 4, 8, 16, 20, and 24

• Treatment Phase: Percentage of Participants Who Achieved an ACR70 Response at Weeks 2, 4, 8, 16, 20 and 24 Based on NRI

  Weeks 2, 4, 8, 16, 20, and 24

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

  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, 72, 76, 80, and 84

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

  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, 72, 76, 80, and 84

Study Arms (4)

E6011 100 milligrams (mg)

EXPERIMENTAL

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.

Drug: E6011

E6011 200 mg

EXPERIMENTAL

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.

Drug: E6011

E6011 400 mg

EXPERIMENTAL

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.

Drug: E6011

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

E6011 DRUG

subcutaneous administration

E6011 100 milligrams (mg); E6011 200 mg; E6011 400 mg

Placebo DRUG

subcutaneous administration

Placebo

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 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

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 (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

Sponsors & Collaborators

• Eisai Co., Ltd.: lead

Study Sites (90)

Eisai Trial Site #1

Nagoya, Aichi-ken, Japan

Location

Eisai Trial Site #2

Nagoya, Aichi-ken, Japan

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Eisai Trial Site #3

Nagoya, Aichi-ken, Japan

Location

Eisai Trial Site #4

Nagoya, Aichi-ken, Japan

Location

Eisai Trial Site #1

Toyohashi, Aichi-ken, Japan

Location

Eisai Trial Site #1

Toyota, Aichi-ken, Japan

Location

Eisai Trial Site #1

Funabashi, Chiba, Japan

Location

Eisai Trial Site #1

Matsuyama, Ehime, Japan

Location

Eisai Trial Site #1

Iizuka, Fukuoka, Japan

Location

Eisai Trial Site #1

Kitakyushu, Fukuoka, Japan

Location

Eisai Trial Site #1

Kurume, Fukuoka, Japan

Location

Eisai Trial Site #2

Kurume, 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

Hakodate, Hokkaido, Japan

Location

Eisai Trial Site #1

Kushiro, 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

Tomakomai, Hokkaido, Japan

Location

Eisai Trial Site #1

Kobe, Hyōgo, Japan

Location

Eisai Trial Site #1

Takarazuka, Hyōgo, Japan

Location

Eisai Trial Site #1

Hitachi, Ibaraki, Japan

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Eisai Trial Site #1

Hitachi-Naka, Ibaraki, Japan

Location

Eisai Trial Site #1

Kasama, Ibaraki, Japan

Location

Eisai Trial Site #1

Komatsu, Ishikawa-ken, Japan

Location

Eisai Trial Site #1

Morioka, Iwate, Japan

Location

Eisai Trial Site #1

Kirishima, Kagoshima-ken, Japan

Location

Eisai Trial Site #1

Yokohama, Kanagawa, Japan

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Eisai Trial Site #2

Yokohama, Kanagawa, Japan

Location

Eisai Trial Site #1

Yamaga, Kumamoto, Japan

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Eisai Trial Site #1

Yokkaichi, Mie-ken, Japan

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Eisai Trial Site #1

Ōsaki, Miyagi, Japan

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Eisai Trial Site #1

Sendai, Miyagi, Japan

Location

Eisai Trial Site #2

Sendai, Miyagi, Japan

Location

Eisai Trial Site #1

Hyūga, Miyazaki, Japan

Location

Eisai Trial site #2

Hyūga, Miyazaki, Japan

Location

Eisai Trial Site #1

Matsumoto, Nagano, Japan

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Eisai Trial Site #1

Isahaya, Nagasaki, Japan

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Eisai Trial Site #1

Ōmura, Nagasaki, Japan

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Eisai Trial Site #1

Sasebo, Nagasaki, Japan

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Eisai Trial Site #1

Nagaoka, Niigata, Japan

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Eisai Trial Site #1

Shibata, Niigata, Japan

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Eisai Trial Site #1

Beppu, Oita Prefecture, Japan

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Eisai Trial Site #1

Tomigusuku, Okinawa, Japan

Location

Eisai Trial Site #1

Kawachi-Nagano, Osaka, Japan

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Eisai Trial Site #1

Ureshino, Saga-ken, Japan

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Eisai Trial Site #1

Hiki, Saitama, Japan

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Eisai Trial Site #1

Kawagoe, Saitama, Japan

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Eisai Trial Site #1

Kawaguchi, Saitama, Japan

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Eisai Trial Site #1

Tokorozawa, Saitama, Japan

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Eisai Trial Site #1

Hamamatsu, Shizuoka, Japan

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Eisai Trial Site #1

Shimotsuke, Tochigi, Japan

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Eisai Trial Site #1

Bunkyo, Tokyo, Japan

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Eisai Trial Site #1

Chūō, Tokyo, Japan

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Eisai Trial Site #1

Fuchū, Tokyo, Japan

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Eisai Trial Site #1

Meguro City, Tokyo, Japan

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Eisai Trial Site #1

Musashino, Tokyo, Japan

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Eisai Trial Site #1

Nakano City, Tokyo, Japan

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Eisai Trial Site #1

Ōme, Tokyo, Japan

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Eisai Trial Site #1

Ōta-ku, Tokyo, Japan

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Eisai Trial Site #1

Setagaya City, Tokyo, Japan

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Eisai Trial Site #1

Shinjuku, Tokyo, Japan

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Eisai Trial Site #2

Shinjuku, Tokyo, Japan

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Eisai Trial Site #1

tabashi City, Tokyo, Japan

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Eisai Trial Site #1

Takaoka, Toyama, Japan

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Eisai Trial Site #1

Nishimuro, Wakayama, Japan

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Eisai Trial Site #1

Shimonoseki, Yamaguchi, Japan

Location

Eisai Trial Site #2

Shimonoseki, Yamaguchi, Japan

Location

Eisai Trial Site #1

Fukui, Japan

Location

Eisai Trial Site #2

Fukuoka, Japan

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Eisai Trial Site #1

Gifu, Japan

Location

Eisai Trial Site #1

Hiroshima, Japan

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Eisai Trial Site #2

Hiroshima, Japan

Location

Eisai Trial Site #3

Hiroshima, Japan

Location

Eisai Trial Site #1

Kagoshima, Japan

Location

Eisai Trial Site #2

Kagoshima, Japan

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Eisai Trial Site #3

Kagoshima, Japan

Location

Eisai Trial Site #1

Kochi, Japan

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Eisai Trial Site #2

Kumamoto, Japan

Location

Eisai Trial Site #1

Miyagi, Japan

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Eisai Trial Site #1

Miyazaki, Japan

Location

Eisai Trial Site #1

Nagano, 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

Saitama, Japan

Location

Eisai Trial Site #1

Shizuoka, Japan

Location

Related Publications (1)

• Tanaka Y, Takeuchi T, Yamanaka H, Nanki T, Umehara H, Yasuda N, Tago F, Kitahara Y, Kawakubo M, Torii K, Hojo S, Kawano T, Imai T. Efficacy and Safety of E6011, an Anti-Fractalkine Monoclonal Antibody, in Patients With Active Rheumatoid Arthritis With Inadequate Response to Methotrexate: Results of a Randomized, Double-Blind, Placebo-Controlled Phase II Study. Arthritis Rheumatol. 2021 Apr;73(4):587-595. doi: 10.1002/art.41555. Epub 2021 Feb 18.

  PMID: 33038062 DERIVED

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: No

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: October 20, 2016
• Primary Completion: February 28, 2018
• Study Completion: September 17, 2019
• Last Updated: June 21, 2021
• Results First Posted: June 21, 2021

Record last verified: 2021-05

Locations

JP (90)