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

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 ≥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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

E6011 400 mg/E6011 200 mg

E6011 400 mg/E6011 400 mg

Placebo/E6011 200 mg

Placebo/E6011 400 mg

Arm Description

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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

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. Data for the Core Treatment Phase from Week 0-10 is reported according to the participant's re-randomization in four arms at Week 12. Data reported for the Extension Phase from Week 2 to Week 24, is the same data for the Core Treatment Phase, but excluding the participants who received at least 1 dose of study drug after Week 24 and had at least 1 postdose primary efficacy measurement after Week 24 to Week 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

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. Data for the Core Treatment Phase from Week 0-10 is reported according to the participant's re-randomization in four arms at Week 12. Data reported for the Extension Phase from Week 2 to Week 24, is the same data for the Core Treatment Phase, but excluding the participants who received at least 1 dose of study drug after Week 24 and had at least 1 postdose primary efficacy measurement after Week 24 to Week 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

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. Data for the Core Treatment Phase from Week 0-10 is reported according to the participant's re-randomization in four arms at Week 12. Data reported for the Extension Phase from Week 2 to Week 24, is the same data for the Core Treatment Phase, but excluding the participants who received at least 1 dose of study drug after Week 24 and had at least 1 postdose primary efficacy measurement after Week 24 to Week 72.

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

A total of 28 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 for the Core Treatment Phase from Week 0-10 is reported according to the participant's re-randomization in four arms at Week 12. Data reported for the Extension Phase from Baseline to Week 24, is the same data for the Core Treatment Phase, but excluding the participants who received at least 1 dose of study drug after Week 24 and had at least 1 postdose primary efficacy measurement after Week 24 to Week 72.

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

A total of 28 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 for the Core Treatment Phase from Week 0-10 is reported according to the participant's re-randomization in four arms at Week 12. Data reported for the Extension Phase from Baseline to Week 24, is the same data for the Core Treatment Phase, but excluding the participants who received at least 1 dose of study drug after Week 24 and had at least 1 postdose primary efficacy measurement after Week 24 to Week 72.

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. Pain 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 for the Core Treatment Phase from Week 0-10 is reported according to the participant's re-randomization in four arms at Week 12. Data reported for the Extension Phase from Baseline to Week 24, is the same data for the Core Treatment Phase, but excluding the participants who received at least 1 dose of study drug after Week 24 and had at least 1 postdose primary efficacy measurement after Week 24 to Week 72.

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 for the Core Treatment Phase from Week 0-10 is reported according to the participant's re-randomization in four arms at Week 12. Data reported for the Extension Phase from Baseline to Week 24, is the same data for the Core Treatment Phase, but excluding the participants who received at least 1 dose of study drug after Week 24 and had at least 1 postdose primary efficacy measurement after Week 24 to Week 72.

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 for the Core Treatment Phase from Week 0-10 is reported according to the participant's re-randomization in four arms at Week 12. Data reported for the Extension Phase from Baseline to Week 24, is the same data for the Core Treatment Phase, but excluding the participants who received at least 1 dose of study drug after Week 24 and had at least 1 postdose primary efficacy measurement after Week 24 to Week 72.

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

Degree of disability was self-evaluated by participant using HAQ-DI.Assessment was made based on activities capable without any aids/devices.20-question instrument assessed degree of difficulty 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 task in that area).Overall score computed as: sum of domain scores and divided by number of domains answered.Total possible score range:0-3 where 0=least difficulty and 3=extreme difficulty.Data for Core Treatment Phase from Week 0-10 is reported according to participant re-randomization in 4 arms at Week 12.Data reported for Extension Phase from Baseline to Week 24,is same data for Core Treatment Phase,but excluding participants who received at least 1 dose of drug and had at least 1 postdose primary efficacy measurement after Week 24-72.

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. A normal CRP value is less than (<) 10 milligram per deciliter (mg/dL). A test result showing a CRP level greater than 10 mg/dL is a sign of chronic disease. Data for the Core Treatment Phase from Week 0-10 is reported according to the participant's re-randomization in four arms at Week 12. Data reported for the Extension Phase from Baseline to Week 24, is the same data for the Core Treatment Phase, but excluding the participants who received at least 1 dose of study drug after Week 24 and had at least 1 postdose primary efficacy measurement after Week 24 to Week 72.

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 for the Core Treatment Phase from Week 0-10 is reported according to the participant's re-randomization in four arms at Week 12. Data reported for the Extension Phase from Baseline to Week 24, is the same data for the Core Treatment Phase, but excluding the participants who received at least 1 dose of study drug after Week 24 and had at least 1 postdose primary efficacy measurement after Week 24 to Week 72.

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 greater than (>) 3.2 and less than or equal to (<=) 5.1=moderate disease activity and value <=3.2=low disease activity, value <2.6=disease remission. A positive change in score indicates worsening, and a negative change indicates improvement. Data for the Core Treatment Phase from Week 0-10 is reported according to the participant's re-randomization in four arms at Week 12. Data reported for the Extension Phase from Baseline to Week 24, is the same data for the Core Treatment Phase, but excluding the participants who received at least 1 dose of study drug after Week 24 and had at least 1 postdose primary efficacy measurement after Week 24 to Week 72.

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 4.1 or above=high disease activity, a value >2.7 and <=4.1=moderate disease activity and a value <=2.7=low disease activity, value <2.3=disease remission. A positive change in score indicates worsening, and a negative change indicates improvement. Data for the Core Treatment Phase from Week 0-10 is reported according to the participant's re-randomization in four arms at Week 12. Data reported for the Extension Phase from Baseline to Week 24, is the same data for the Core Treatment Phase, but excluding the participants who received at least 1 dose of study drug after Week 24 and had at least 1 postdose primary efficacy measurement after Week 24 to Week 72.

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 (score range as 0-28), swollen joint counts of 28 (score range as 0-28), participant's global assessment of disease activity (score range as 0-10), physician global assessment of disease activity score (score range as 0-10), and CRP value (score range as 0-10). Total score ranged between 0-86. SDAI score of 26 or above=high disease activity, a value >11 and <=26=moderate disease activity and value <=11=low disease activity, value <=3.3=disease remission. Higher scores indicated higher disease activity. Data for the Core Treatment Phase from Week 0-10 is reported according to the participant's re-randomization in four arms at Week 12. Data reported for the Extension Phase from Baseline to Week 24, is the same data for the Core Treatment Phase, but excluding the participants who received at least 1 dose of study drug after Week 24 and had at least 1 postdose primary efficacy measurement after Week 24 to Week 72.

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 (score range as 0-28), swollen joint counts of 28 (score range as 0-28), participant's global assessment of disease activity (score range as 0-10) and physician global assessment of disease activity (score range as 0-10). Total score ranged between 0-76. CDAI score of 22 or above=high disease activity, a value >10 and <=22=moderate disease activity, a value <=10=low disease activity, and a value <=2.8=disease remission. Higher scores indicated higher disease activity. Data for the Core Treatment Phase from Week 0-10 is reported according to the participant's re-randomization in four arms at Week 12. Data reported for the Extension Phase from Baseline to Week 24, is the same data for the Core Treatment Phase, but excluding the participants who received at least 1 dose of study drug after Week 24 and had at least 1 postdose primary efficacy measurement after Week 24 to Week 72.

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-ESR 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 for the Core Treatment Phase from Week 0-10 is reported according to the participant's re-randomization in four arms at Week 12. Data reported for the Extension Phase from Week 2 to Week 24, is the same data for the Core Treatment Phase, but excluding the participants who received at least 1 dose of study drug after Week 24 and had at least 1 postdose primary efficacy measurement after Week 24 to Week 72.

Number of Participants With a EULAR Good, Moderate or No Response Using DAS28-CRP at Each Visit Based on NRI

The Disease Activity Score Based on 28-joints Count-CRP 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 for the Core Treatment Phase from Week 0-10 is reported according to the participant's re-randomization in four arms at Week 12. Data reported for the Extension Phase from Week 2 to Week 24, is the same data for the Core Treatment Phase, but excluding the participants who received at least 1 dose of study drug after Week 24 and had at least 1 postdose primary efficacy measurement after Week 24 to Week 72.

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

The SDAI was calculated from tender joint counts of 28 (score range as 0-28), swollen joint counts of 28 (score range as 0-28), participant's global assessment of disease activity (score range as 0-10), physician global assessment of disease activity score (score range as 0-10), and CRP value (score range as 0-10). Total score ranged between 0-86. SDAI score of 86 or above=high disease activity, a value >11 and <=26=moderate disease activity, a value >=3.4 and <=11=low disease activity. Higher scores indicated higher disease activity. SDAI Remission was defined as SDAI score <=3.3. Data for Core Treatment Phase from Week 0-10 is reported according to participant's re-randomization in four arms at Week 12. Data reported for Extension Phase from Week 2 to Week 24, is same data for Core Treatment Phase, but excluding participants who received at least 1 dose of study drug after Week 24 and had at least 1 postdose primary efficacy measurement after Week 24 to Week 72.

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

The CDAI was calculated from tender joint counts of 28 (score range as 0-28), swollen joint counts of 28 (score range as 0-28), participant's global assessment of disease activity (score range as 0-10), and physician global assessment of disease activity score (score range as 0-10). Total score ranged between 0-76. CDAI score of 76 or above=high disease activity, a value >10 and <=22=moderate disease activity, a value >2.9 and <=10=low disease activity. Higher scores indicated higher disease activity. CDAI Remission was defined as CDAI score <=2.8. Data for the Core Treatment Phase from Week 0-10 is reported according to the participant's re-randomization in four arms at Week 12. Data reported for the Extension Phase from Week 2 to Week 24, is the same data for the Core Treatment Phase, but excluding the participants who received at least 1 dose of study drug after Week 24 and had at least 1 postdose primary efficacy measurement after Week 24 to Week 72.

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 66 <=1; CRP <=1 mg/dL; and disease activity assessments VAS (mm) by participants <=10. Data for the Core Treatment Phase from Week 0-10 is reported according to the participant's re-randomization in four arms at Week 12. Data reported for the Extension Phase from Week 2 to Week 24, is the same data for the Core Treatment Phase, but excluding the participants who received at least 1 dose of study drug after Week 24 and had at least 1 postdose primary efficacy measurement after Week 24 to Week 72.

Full Information

NCT ID

NCT02960490

First Posted

November 3, 2016

Last Updated

July 28, 2021

Sponsor

Eisai Co., Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT02960490

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2019

Overall Recruitment Status

Completed

Study Start Date

November 26, 2016 (Actual)

Primary Completion Date

May 16, 2018 (Actual)

Study Completion Date

November 25, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eisai Co., Ltd.

4. Oversight

Data Monitoring Committee

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 biologics.

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

66 (Actual)

8. Arms, Groups, and Interventions

Arm Title

E6011 400 mg/E6011 200 mg

Arm Type

Experimental

Arm Description

Arm Title

E6011 400 mg/E6011 400 mg

Arm Type

Experimental

Arm Description

Arm Title

Placebo/E6011 200 mg

Arm Type

Experimental

Arm Description

Arm Title

Placebo/E6011 400 mg

Arm Type

Experimental

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

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)

Description

Time Frame

Week 12

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame