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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02960490
• Date of registration: 03/11/2016
• Prospective Registration: Yes
• Primary sponsor: Eisai Co., Ltd.
• Public title: A Phase 2 Study of E6011 in Subjects With Rheumatoid Arthritis Inadequately Responding to Biologics
• Scientific title: A Phase 2 Study of E6011 in Subjects With Rheumatoid Arthritis Inadequately Responding to Biologics
• Date of first enrolment: November 26, 2016
• Target sample size: 64
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02960490
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Japan

Key inclusion & exclusion criteria

Inclusion Criteria:

- Aged =18 and <75 years old at the time of informed consent

- Diagnosed with rheumatoid arthritis (RA) under the 1987 American College of
Rheumatology (ACR) or 2010 ACR/European League Against Rheumatism (EULAR) criteria =12
weeks before informed consent

- Received biologics treatment under approved dosage and administration for =12 weeks
but discontinued it before screening because of inadequate response

- History of biologics treatment should be limited to 2 agents among adalimumab,
infliximab, golimumab, certolizumab pegol, etanercept, tocilizumab, and abatacept
(including biosimilars).

- Presented =6 tender joints (out of 68 joints) and =6 swollen joints (out of 66 joints)
in the Screening and Observation Phases

- Can continue stable dose regimen of methotrexate at 6 to 16 milligrams (mg)/week from
4 weeks before starting the study treatment until completion of the Extension Phase
(or until study discontinuation)

- C-reactive protein (CRP) level =0.6 mg/deciliter (dL) or erythrocyte sedimentation
rate (ESR) =28 millimeters per hour (mm/hr) in the Screening Phase

- Weighs =30 kilograms (kg) and =100 kg in the Screening Phase

- Has voluntarily consented, in writing, to participate in this study. If a participant
is below the age of 20, also consented, in writing by a legally acceptable
representative.

- Has been thoroughly briefed on the conditions for participation in the study, is able
to understand, and is willing and able to comply with all aspects of the protocol

Exclusion Criteria:

- Any history or complication of inflammatory arthritic disorder other than RA or
Sjogren's syndrome

- Meets the ACR 1991 Revised Criteria for the Classification of Global Functional Status
in RA Class IV in the Screening Phase

- Received immunoglobulin preparations or blood products within 24 weeks before starting
the study treatment

- Received a live vaccine within 12 weeks before starting the study treatment, or is
planning to receive

- Evidence of clinically significant disease (e.g., cardiac, respiratory,
gastrointestinal, or renal disease) that could affect the participant's safety or
interfere with the study assessments in the opinion of the investigator or
subinvestigator

- Complication of uncontrolled disorders such as acute cardiac infarction, unstable
angina, brain infarct, or symptomatic intracerebral hemorrhage

- History of severe allergy (shock or anaphylactoid symptoms)

- History or current clinical condition of malignant tumor, lymphoma, leukemia, or
lymphoproliferative disease, except for skin carcinoma (epithelial carcinoma or basal
cell carcinoma) and cervix carcinoma which has completely excised and without
metastasis or recurrence for more than 5 years before informed consent

- Immunodeficiency or history of human immunodeficiency virus (HIV) infection

- Infection requiring hospitalization or intravenous administration of antibiotics or
disease requiring administration of antivirus drugs (e.g., herpes zoster) within 4
weeks before starting the study treatment

- History of tuberculosis or current complication of active tuberculosis

- History of clinically important vasculitis

- Tested positive for any of the following in the Screening Phase: HIV, hepatitis B
virus surface antigen (HBs antigen), hepatitis B virus surface antibody (HBs
antibody), hepatitis B virus core antibody (HBc antibody), hepatitis B virus
deoxyribonucleic acid (HBV DNA), hepatitis C virus antibody (HCV antibody), human
T-lymphotrophic virus Type I antibody (HTLV-1 antibody), or syphilis

- Positive in tuberculosis test (QuantiFERON®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 (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




Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis

Intervention(s)

Drug: Placebo

Drug: E6011

Primary Outcome(s)

American College of Rheumatology 20 (ACR20) response rate at Week 12 [Time Frame: Week 12]

Secondary Outcome(s)

Change from baseline in DAS28-ESR values at each visit [Time Frame: Baseline; up to Week 104]

Change from baseline in ESR values at each visit [Time Frame: Baseline; up to Week 104]

ACR20 response rate at each visit [Time Frame: up to Week 104]

European League against Rheumatism (EULAR) response criteria at each visit [Time Frame: up to Week 104]

Change from baseline in scores on the health assessment questionnaire at each visit [Time Frame: Baseline; up to Week 104]

Change from baseline in scores on the visual analog scale for disease activity assessed by participants and by physicians at each visit [Time Frame: Baseline; up to Week 104]

Mean disease activity score 28 (DAS28)-ESR values at each visit [Time Frame: up to Week 104]

Mean scores on the simple disease activity index (SDAI) scale at each visit [Time Frame: up to Week 104]

DAS28-ESR remission rate at each visit [Time Frame: up to Week 104]

Mean scores on the health assessment questionnaire at each visit [Time Frame: up to Week 104]

ACR70 response rate at each visit [Time Frame: up to Week 104]

CDAI remission rate at each visit [Time Frame: up to Week 104]

Change from baseline in scores on the SDAI scale at each visit [Time Frame: Baseline; up to Week 104]

Change from baseline in the number of swollen joints at each visit [Time Frame: Baseline; up to Week 104]

Mean scores on the visual analog scale for disease activity assessed by participants and by physicians at each visit [Time Frame: up to Week 104]

Change from baseline in scores on the CDAI scale at each visit [Time Frame: Baseline; up to Week 104]

Mean erythrocyte sedimentation rate (ESR) values at each visit [Time Frame: up to Week 104]

DAS28-CRP remission rate at each visit [Time Frame: up to Week 104]

Mean C-reactive protein (CRP) values at each visit [Time Frame: up to Week 104]

Number of swollen joints at each visit [Time Frame: up to Week 104]

Mean DAS28-CRP values at each visit [Time Frame: up to Week 104]

Number of tender joints at each visit [Time Frame: up to Week 104]

Boolean remission rate at each visit [Time Frame: up to Week 104]

Change from baseline in CRP values at each visit [Time Frame: Baseline; up to Week 104]

ACR50 response rate at each visit [Time Frame: up to Week 104]

Change from baseline in DAS28-CRP values at each visit [Time Frame: Baseline; up to Week 104]

Change from baseline in scores on the visual analog scale for pain assessment assessed by participants and by physicians at each visit [Time Frame: Baseline; up to Week 104]

Change from baseline in the number of tender joints at each visit [Time Frame: Baseline; up to Week 104]

Mean scores on the clinical disease activity index (CDAI) scale at each visit [Time Frame: up to Week 104]

Mean scores on the visual analog scale for pain assessment assessed by participants and by physicians at each visit [Time Frame: up to Week 104]

SDAI remission rate at each visit [Time Frame: up to Week 104]

Secondary ID(s)

E6011-J081-202

Source(s) of Monetary Support

Please refer to primary and secondary sponsors