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

Primary Purpose

Rheumatoid Arthritis

Status

Completed

Phase

Phase 2

Locations

Japan

Study Type

Interventional

Intervention

E6011

Placebo

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring E6011, rheumatoid arthritis

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Arm Label

E6011 100 milligrams (mg)

E6011 200 mg

E6011 400 mg

Placebo

Arm 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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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

The ACR20 response was defined as if the following 3 criteria (ACR components) were met: >=20% reduction from baseline in the TJC in 68 joints (TJC68); >=20% reduction from baseline in the 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 (VAS), Participant's Global Assessment of Disease Activity (VAS), Participant's Assessment of Pain (VAS), HAQ-DI, and CRP.

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

The ACR50 response was defined as if the following 3 criteria (ACR components) were met: >=50% reduction from baseline in the TJC in 68 joints (TJC68); >=50% reduction from baseline in the SJC in 66 joints (SJC66); >=50% reduction from baseline in at least 3 of the following 5 assessments: Physician's Global Assessment of Disease Activity (VAS), Participant's Global Assessment of Disease Activity (VAS), Participant's Assessment of Pain (VAS), HAQ-DI, and CRP.

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

The ACR70 response was defined as if the following 3 criteria (ACR components) were met: >=70% reduction from baseline in the TJC in 68 joints (TJC68); >=70% reduction from baseline in the SJC in 66 joints (SJC66); >=70% reduction from baseline in at least 3 of the following 5 assessments: Physician's Global Assessment of Disease Activity (VAS), Participant's Global Assessment of Disease Activity (VAS), Participant's Assessment of Pain (VAS), HAQ-DI, and CRP.

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

A total of 68 joints were examined for tenderness by applying pressure to the joint line or by moving joints through their respective ranges of motion. Joints were examined for tenderness by applying pressure to the joint line or by moving joints through their respective ranges of motion. Tender joints were marked with tick or cross in corresponding frames of the Assessment Sheet for Tender Joint Counts. Data reported for the Extension Phase from Baseline to Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase.

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

A total of 66 joints (minus 2 hip joints from evaluated tender joints) were examined for swollen joints. Swollen joints were marked with open circles in corresponding frames of the Assessment Sheet for Swollen Joint Counts. Data reported for the Extension Phase from Baseline to Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase.

Change From Baseline in Participant's Assessment of Pain Based on VAS Score at Each Visit Based on LOCF

Intensity and severity of pain associated with rheumatoid arthritis (RA) were indicated by the participant on a score sheet, Pain/disease activity assessments reported by the participant, by placing a mark on a 100 millimeter (mm) horizontal VAS. The scale ranged from 0-100 mm, where 0 indicated no disease activity (symptom free and no arthritis symptoms) and 100 represented maximum disease activity (maximum arthritis disease activity). Data reported for the Extension Phase from Baseline to Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase.

Change From Baseline in Participant's Global Assessment of Disease Activity Based on VAS Score at Each Visit Based on LOCF

Participants were evaluated on their disease activity of RA, and entered the result on the score sheet, disease activity assessments reported by the participant, by placing a mark on a 100 mm horizontal VAS. The scale ranged from 0-100 mm, where 0 indicated no disease activity (symptom free and no arthritis symptoms) and 100 represented maximum disease activity (maximum arthritis disease activity). Data reported for the Extension Phase from Baseline to Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase.

Change From Baseline in Physician's Global Assessment of Disease Activity Scale Based on VAS Score at Each Visit Based on LOCF

The Physician's Global Assessment of Disease Activity was recorded using the 100 mm horizontal VAS. Physician rated participant's RA disease activity on a scale ranged from 0-100 mm, where 0 indicated no disease activity (no arthritis) and 100 represented maximum disease activity (maximum arthritis). Data reported for the Extension Phase from Baseline to Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase.

Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Each Visit Based on LOCF

The degree of disability was self-evaluated by the participant using the HAQ-DI. The assessment was made based on the activities capable without any aids or devices. The 20-question instrument assessed the degree of difficulty a person had in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area were scored from 0, indicated no difficulty, to 3, indicated inability to perform a task in that area. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range: 0-3 where 0 = least difficulty and 3 = extreme difficulty. Data reported for the Extension Phase from Baseline to Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase.

Change From Baseline in C-reactive Protein (CRP) Values at Each Visit Based on LOCF

CRP of each participants was measured as a part of blood biochemical tests. Data reported for the Extension Phase from Baseline to Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase.

Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Values at Each Visit Based on LOCF

ESR were a type of blood test. An ESR was used to monitor the arthritis condition. Data reported for the Extension Phase from Baseline to Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase.

Change From Baseline in Disease Activity Score 28 (DAS28)-ESR Values at Each Visit Based on LOCF

The DAS28 index was a composite score of weighted components including tender joint counts of 28, swollen joint counts of 28, participant global assessment of disease activity score, and ESR value. Total score ranged between 0-10. A DAS28-ESR score of 5.1 or above = high disease activity, a value between 3.2 and 5.1 = moderate disease activity and value between 2.6 and 3.2 = low disease activity, value <2.6 = disease remission. A positive change in score indicates worsening, and a negative change indicates improvement. Data reported for the Extension Phase from Baseline to Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase.

Change From Baseline in DAS28-CRP Values at Each Visit Based on LOCF

The DAS28 index was a composite score of weighted components including tender joint counts of 28, swollen joint counts of 28, participant global assessment of disease activity score, and CRP value. Total score ranged between 0-10. A DAS28-CRP score of 5.1 or above = high disease activity, a value between 3.2 and 5.1 = moderate disease activity and value between 2.6 and 3.2 = low disease activity, value <2.6 = disease remission. A positive change in score indicates worsening, and a negative change indicates improvement. Data reported for the Extension Phase from Baseline to Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase.

Change From Baseline in Simple Disease Activity Index (SDAI) Values at Each Visit Based on LOCF

The SDAI was calculated from tender joint counts of 28, swollen joint counts of 28, participant's global assessment of disease activity, physician global assessment of disease activity score, and CRP value. Total score ranged between 0-86. SDAI score of 26 or above = high disease activity, a value between 11 and 26 = moderate disease activity and value less than or equal to (<=) 11 = low disease activity, value <=33 = disease remission. Higher scores indicated higher disease activity. Data reported for the Extension Phase from Baseline to Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase.

Change From Baseline in Clinical Disease Activity Index (CDAI) Values at Each Visit Based on LOCF

The CDAI was calculated from tender joint counts of 28, swollen joint counts of 28, participant's global assessment of disease activity, physician global assessment of disease activity score, and CRP value. Total score ranged between 0-76. CDAI score of 22 or above = high disease activity, a value between 10 and 22 = moderate disease activity and value less than or equal to <=10 = low disease activity, value <=2.8 = disease remission. Higher scores indicated higher disease activity. Data reported for the Extension Phase from Baseline to Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase.

Number of Participants With a European League Against Rheumatism (EULAR) Good, Moderate or No Response Using DAS28-ESR at Each Visit Based on NRI

The Disease Activity Score Based on 28-joints Count based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline >1.2 with DAS28 <=3.2; moderate responders: change from baseline >1.2 with DAS28 >3.2 to <=5.1 or change from baseline >0.6 to <=1.2 with DAS28 <=5.1; non-responders: change from baseline <=0.6 or change from baseline >0.6 and <=1.2 with DAS28 >5.1. Data reported for the Extension Phase from Week 2 to Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase.

Number of Participants With a EULAR Good or Moderate Response Using DAS28-CRP at Each Visit Based on NRI

Percentage of Participants Who Achieved SDAI Remission at Each Visit Based on NRI

The SDAI was calculated from tender joint counts of 28, swollen joint counts of 28, participant's global assessment of disease activity, physician global assessment of disease activity score, and CRP value. Total score ranged between 0-86. SDAI score of 26 or above = high disease activity, a value between 11 and 26 = moderate disease activity and value <=11 = low disease activity. Higher scores indicated higher disease activity. SDAI Remission was defined as SDAI score <=3.3. Data reported for the Extension Phase from Week 2 to Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase.

Percentage of Participants Who Achieved CDAI Remission at Each Visit Based on NRI

The CDAI was calculated from tender joint counts of 28, swollen joint counts of 28, participant's global assessment of disease activity, physician global assessment of disease activity score, and CRP value. Total score ranged between 0-76. CDAI score of 22 or above = high disease activity, a value between 10 and 22 = moderate disease activity and value less than or equal to <=10 = low disease activity. Higher scores indicated higher disease activity. CDAI Remission was defined as CDAI score <=2.8. Data reported for the Extension Phase from Week 2 to Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase.

Percentage of Participants Who Achieved Boolean Remission at Each Visit Based on NRI

Boolean remission criteria was defined as: tender joint count 68 <=1; swollen joint count 68 <=1; CRP <=1 mg/dL; and disease activity assessments VAS (mm) by participants <=1. Data reported for the Extension Phase from Week 2 to Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase.

Change From Baseline in Modified Total Sharp Score (mTSS) at Each Visit Based on Observed Cases (OC)

The mTSS was a measure of change in joint health. X-rays of hands, wrists, and feet (including distal interphalangeal joints) were obtained. Totals for hands and feet for erosion scores (range 0 to 320) and joint space narrowing scores (range 0 to 208) were calculated and added to obtain the mTSS (range = 0 [normal] to 528 [maximal disease]). An increase in mTSS from Baseline represents disease progression and/or joint worsening; no progression was defined as a change of <=0.5. Data reported for the Extension Phase from Baseline and Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase.

Full Information

NCT ID

NCT02960438

First Posted

November 3, 2016

Last Updated

May 26, 2021

Sponsor

Eisai Co., Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT02960438

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2021

Overall Recruitment Status

Completed

Study Start Date

October 20, 2016 (Actual)

Primary Completion Date

February 28, 2018 (Actual)

Study Completion Date

September 17, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eisai Co., Ltd.

4. Oversight

5. Study Description

Brief Summary

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rheumatoid Arthritis

Keywords

E6011, rheumatoid arthritis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

273 (Actual)

8. Arms, Groups, and Interventions

Arm Title

E6011 100 milligrams (mg)

Arm Type

Experimental

Arm Description

Arm Title

E6011 200 mg

Arm Type

Experimental

Arm Description

Arm Title

E6011 400 mg

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

E6011

Intervention Description

subcutaneous administration

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

subcutaneous administration

Primary Outcome Measure Information:

Title

Treatment Phase: Percentage of Participants Who Achieved an American College of Rheumatology 20 (ACR20) Response at Week 12 Based on Non-responder Imputation (NRI)

Description

Time Frame

Week 12

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

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

Title

Change From Baseline in Participant's Assessment of Pain Based on VAS Score at Each Visit Based on LOCF

Description

Time Frame

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

Title

Change From Baseline in Participant's Global Assessment of Disease Activity Based on VAS Score at Each Visit Based on LOCF

Description

Time Frame

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

Title

Change From Baseline in Physician's Global Assessment of Disease Activity Scale Based on VAS Score at Each Visit Based on LOCF

Description

Time Frame

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

Title

Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Each Visit Based on LOCF

Description

Time Frame

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

Title

Change From Baseline in C-reactive Protein (CRP) Values at Each Visit Based on LOCF

Description

Time Frame

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

Title

Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Values at Each Visit Based on LOCF

Description

Time Frame

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

Title

Change From Baseline in Disease Activity Score 28 (DAS28)-ESR Values at Each Visit Based on LOCF

Description

Time Frame

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

Title

Change From Baseline in DAS28-CRP Values at Each Visit Based on LOCF

Description

The DAS28 index was a composite score of weighted components including tender joint counts of 28, swollen joint counts of 28, participant global assessment of disease activity score, and CRP value. Total score ranged between 0-10. A DAS28-CRP score of 5.1 or above = high disease activity, a value between 3.2 and 5.1 = moderate disease activity and value between 2.6 and 3.2 = low disease activity, value <2.6 = disease remission. A positive change in score indicates worsening, and a negative change indicates improvement. Data reported for the Extension Phase from Baseline to Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase.

Time Frame

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

Title

Change From Baseline in Simple Disease Activity Index (SDAI) Values at Each Visit Based on LOCF

Description

Time Frame

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

Title

Change From Baseline in Clinical Disease Activity Index (CDAI) Values at Each Visit Based on LOCF

Description

Time Frame

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

Title

Number of Participants With a European League Against Rheumatism (EULAR) Good, Moderate or No Response Using DAS28-ESR at Each Visit Based on NRI

Description

Time Frame

Treatment Phase: 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

Title

Number of Participants With a EULAR Good or Moderate Response Using DAS28-CRP at Each Visit Based on NRI

Description

Time Frame

Treatment Phase: 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

Title

Percentage of Participants Who Achieved SDAI Remission at Each Visit Based on NRI

Description

The SDAI was calculated from tender joint counts of 28, swollen joint counts of 28, participant's global assessment of disease activity, physician global assessment of disease activity score, and CRP value. Total score ranged between 0-86. SDAI score of 26 or above = high disease activity, a value between 11 and 26 = moderate disease activity and value <=11 = low disease activity. Higher scores indicated higher disease activity. SDAI Remission was defined as SDAI score <=3.3. Data reported for the Extension Phase from Week 2 to Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase.

Time Frame

Treatment Phase: 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, 84, 88, 92, 96, 100, and 104

Title

Percentage of Participants Who Achieved CDAI Remission at Each Visit Based on NRI

Description

The CDAI was calculated from tender joint counts of 28, swollen joint counts of 28, participant's global assessment of disease activity, physician global assessment of disease activity score, and CRP value. Total score ranged between 0-76. CDAI score of 22 or above = high disease activity, a value between 10 and 22 = moderate disease activity and value less than or equal to <=10 = low disease activity. Higher scores indicated higher disease activity. CDAI Remission was defined as CDAI score <=2.8. Data reported for the Extension Phase from Week 2 to Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase.

Time Frame

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, 72, 76, 80, and 84

Title

Percentage of Participants Who Achieved Boolean Remission at Each Visit Based on NRI

Description

Time Frame

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, 72, 76, 80, and 84

Title

Change From Baseline in Modified Total Sharp Score (mTSS) at Each Visit Based on Observed Cases (OC)

Description

Time Frame

Treatment Phase: Baseline and Week 24; Extension Phase: Baseline, Weeks 24, 52, 76, and 104

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility 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

Facility Information:

Facility Name

Eisai Trial Site #1

City

Nagoya

State/Province

Aichi

Country

Japan

Facility Name

Eisai Trial Site #2

City

Nagoya

State/Province

Aichi

Country

Japan

Facility Name

Eisai Trial Site #3

City

Nagoya

State/Province

Aichi

Country

Japan

Facility Name

Eisai Trial Site #4

City

Nagoya

State/Province

Aichi

Country

Japan

Facility Name

Eisai Trial Site #1

City

Toyohashi

State/Province

Aichi

Country

Japan

Facility Name

Eisai Trial Site #1

City

Toyota

State/Province

Aichi

Country

Japan

Facility Name

Eisai Trial Site #1

City

Funabashi

State/Province

Chiba

Country

Japan

Facility Name

Eisai Trial Site #1

City

Matsuyama

State/Province

Ehime

Country

Japan

Facility Name

Eisai Trial Site #1

City

Iizuka

State/Province

Fukuoka

Country

Japan

Facility Name

Eisai Trial Site #1

City

Kitakyushu

State/Province

Fukuoka

Country

Japan

Facility Name

Eisai Trial Site #1

City

Kurume

State/Province

Fukuoka

Country

Japan

Facility Name

Eisai Trial Site #2

City

Kurume

State/Province

Fukuoka

Country

Japan

Facility Name

Eisai Trial Site #1

City

Takasaki

State/Province

Gunma

Country

Japan

Facility Name

Eisai Trial Site #2

City

Takasaki

State/Province

Gunma

Country

Japan

Facility Name

Eisai Trial Site #1

City

Asahikawa

State/Province

Hokkaido

Country

Japan

Facility Name

Eisai Trial Site #1

City

Hakodate

State/Province

Hokkaido

Country

Japan

Facility Name

Eisai Trial Site #1

City

Kushiro

State/Province

Hokkaido

Country

Japan

Facility Name

Eisai Trial Site #1

City

Sapporo

State/Province

Hokkaido

Country

Japan

Facility Name

Eisai Trial Site #2

City

Sapporo

State/Province

Hokkaido

Country

Japan

Facility Name

Eisai Trial Site #3

City

Sapporo

State/Province

Hokkaido

Country

Japan

Facility Name

Eisai Trial Site #1

City

Tomakomai

State/Province

Hokkaido

Country

Japan

Facility Name

Eisai Trial Site #1

City

Kobe

State/Province

Hyogo

Country

Japan

Facility Name

Eisai Trial Site #1

City

Takarazuka

State/Province

Hyogo

Country

Japan

Facility Name

Eisai Trial Site #1

City

Hitachinaka

State/Province

Ibaraki

Country

Japan

Facility Name

Eisai Trial Site #1

City

Hitachi

State/Province

Ibaraki

Country

Japan

Facility Name

Eisai Trial Site #1

City

Kasama

State/Province

Ibaraki

Country

Japan

Facility Name

Eisai Trial Site #1

City

Komatsu

State/Province

Ishikawa

Country

Japan

Facility Name

Eisai Trial Site #1

City

Morioka

State/Province

Iwate

Country

Japan

Facility Name

Eisai Trial Site #1

City

Kirishima

State/Province

Kagoshima

Country

Japan

Facility Name

Eisai Trial Site #1

City

Yokohama

State/Province

Kanagawa

Country

Japan

Facility Name

Eisai Trial Site #2

City

Yokohama

State/Province

Kanagawa

Country

Japan

Facility Name

Eisai Trial Site #1

City

Yamaga

State/Province

Kumamoto

Country

Japan

Facility Name

Eisai Trial Site #1

City

Yokkaichi

State/Province

Mie

Country

Japan

Facility Name

Eisai Trial Site #1

City

Osaki

State/Province

Miyagi

Country

Japan

Facility Name

Eisai Trial Site #1

City

Sendai

State/Province

Miyagi

Country

Japan

Facility Name

Eisai Trial Site #2

City

Sendai

State/Province

Miyagi

Country

Japan

Facility Name

Eisai Trial Site #1

City

Hyuga

State/Province

Miyazaki

Country

Japan

Facility Name

Eisai Trial site #2

City

Hyuga

State/Province

Miyazaki

Country

Japan

Facility Name

Eisai Trial Site #1

City

Matsumoto

State/Province

Nagano

Country

Japan

Facility Name

Eisai Trial Site #1

City

Isahaya

State/Province

Nagasaki

Country

Japan

Facility Name

Eisai Trial Site #1

City

Omura

State/Province

Nagasaki

Country

Japan

Facility Name

Eisai Trial Site #1

City

Sasebo

State/Province

Nagasaki

Country

Japan

Facility Name

Eisai Trial Site #1

City

Nagaoka

State/Province

Niigata

Country

Japan

Facility Name

Eisai Trial Site #1

City

Shibata

State/Province

Niigata

Country

Japan

Facility Name

Eisai Trial Site #1

City

Beppu

State/Province

Oita

Country

Japan

Facility Name

Eisai Trial Site #1

City

Tomigusuku

State/Province

Okinawa

Country

Japan

Facility Name

Eisai Trial Site #1

City

Kawachinagano

State/Province

Osaka

Country

Japan

Facility Name

Eisai Trial Site #1

City

Ureshino

State/Province

Saga

Country

Japan

Facility Name

Eisai Trial Site #1

City

Hiki

State/Province

Saitama

Country

Japan

Facility Name

Eisai Trial Site #1

City

Kawagoe

State/Province

Saitama

Country

Japan

Facility Name

Eisai Trial Site #1

City

Kawaguchi

State/Province

Saitama

Country

Japan

Facility Name

Eisai Trial Site #1

City

Tokorozawa

State/Province

Saitama

Country

Japan

Facility Name

Eisai Trial Site #1

City

Hamamatsu

State/Province

Shizuoka

Country

Japan

Facility Name

Eisai Trial Site #1

City

Shimotsuke

State/Province

Tochigi

Country

Japan

Facility Name

Eisai Trial Site #1

City

Bunkyo

State/Province

Tokyo

Country

Japan

Facility Name

Eisai Trial Site #1

City

Chuo

State/Province

Tokyo

Country

Japan

Facility Name

Eisai Trial Site #1

City

Fuchu

State/Province

Tokyo

Country

Japan

Facility Name

Eisai Trial Site #1

City

Itabashi

State/Province

Tokyo

Country

Japan

Facility Name

Eisai Trial Site #1

City

Meguro

State/Province

Tokyo

Country

Japan

Facility Name

Eisai Trial Site #1

City

Musashino

State/Province

Tokyo

Country

Japan

Facility Name

Eisai Trial Site #1

City

Nakano

State/Province

Tokyo

Country

Japan

Facility Name

Eisai Trial Site #1

City

Ome

State/Province

Tokyo

Country

Japan

Facility Name

Eisai Trial Site #1

City

Ota

State/Province

Tokyo

Country

Japan

Facility Name

Eisai Trial Site #1

City

Setagaya

State/Province

Tokyo

Country

Japan

Facility Name

Eisai Trial Site #1

City

Shinjuku

State/Province

Tokyo

Country

Japan

Facility Name

Eisai Trial Site #2

City

Shinjuku

State/Province

Tokyo

Country

Japan

Facility Name

Eisai Trial Site #1

City

Takaoka

State/Province

Toyama

Country

Japan

Facility Name

Eisai Trial Site #1

City

Nishimuro

State/Province

Wakayama

Country

Japan

Facility Name

Eisai Trial Site #1

City

Shimonoseki

State/Province

Yamaguchi

Country

Japan

Facility Name

Eisai Trial Site #2

City

Shimonoseki

State/Province

Yamaguchi

Country

Japan

Facility Name

Eisai Trial Site #1

City

Fukui

Country

Japan

Facility Name

Eisai Trial Site #2

City

Fukuoka

Country

Japan

Facility Name

Eisai Trial Site #1

City

Gifu

Country

Japan

Facility Name

Eisai Trial Site #1

City

Hiroshima

Country

Japan

Facility Name

Eisai Trial Site #2

City

Hiroshima

Country

Japan

Facility Name

Eisai Trial Site #3

City

Hiroshima

Country

Japan

Facility Name

Eisai Trial Site #1

City

Kagoshima

Country

Japan

Facility Name

Eisai Trial Site #2

City

Kagoshima

Country

Japan

Facility Name

Eisai Trial Site #3

City

Kagoshima

Country

Japan

Facility Name

Eisai Trial Site #1

City

Kochi

Country

Japan

Facility Name

Eisai Trial Site #2

City

Kumamoto

Country

Japan

Facility Name

Eisai Trial Site #1

City

Miyagi

Country

Japan

Facility Name

Eisai Trial Site #1

City

Miyazaki

Country

Japan

Facility Name

Eisai Trial Site #1

City

Nagano

Country

Japan

Facility Name

Eisai Trial Site #1

City

Nagasaki

Country

Japan

Facility Name

Eisai Trial Site #2

City

Nagasaki

Country

Japan

Facility Name

Eisai Trial Site #3

City

Nagasaki

Country

Japan

Facility Name

Eisai Trial Site #1

City

Oita

Country

Japan

Facility Name

Eisai Trial Site #1

City

Saitama

Country

Japan

Facility Name

Eisai Trial Site #1

City

Shizuoka

Country

Japan

12. IPD Sharing Statement

Citations:

PubMed Identifier

33038062

Citation

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.

Results Reference

derived

Learn more about this trial

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

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

Rheumatoid Arthritis

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial