A Study of E6011 in Japanese Subjects With Rheumatoid Arthritis

Study Overview
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Brief Summary
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This study consist of treatment phase (12 weeks) and extension phase (40 weeks). This study is a multicenter, open-label, uncontrolled, multiple ascending dose (MAD) study to evaluate mainly the safety and tolerability of 12-week repeated subcutaneous administration of E6011 in Japanese subjects with Rheumatoid Arthritis. First 12 subjects will enroll as 100 mg group, next 12 subjects will enroll as 200 mg group, and last 9 subjects will enroll as 400 mg group. A total of 33 subjects will receive repeated subcutaneous administration of E6011. Subjects who roll over onto the Extension phase will have continued monitoring until 52 weeks after the initial administration.

Official Title
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A Phase 1/2 Study of Repeated Subcutaneous E6011 Administration in Japanese Subjects With Rheumatoid Arthritis

Conditions
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Arthritis, Rheumatoid

Intervention / Treatment
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* Drug: E6011


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Subjects must meet all of the following criteria to be included in this study: Japanese patients aged 20 to 64 years old at the time of informed consent. Diagnosed with rheumatoid arthritis (RA) who meet the 1987 ACR or 2010 ACR/EULAR criteria. Presenting tenderness in more than 4 joints (out of 68) and swelling in more than 4 joints (out of 66) at Screening and Observation phase. Never been treated with non-anti-TNF biologics or never been treated with 2 or more anti-TNF agents. Subjects with greater than or equal to 0.6 mg/dL of high-sensitivity CRP (hs-CRP) level or greater than or equal to 28 mm/hr of erythrocyte sedimentation rate (ESR) at Screening. Weighs greater than or equal to 30 kg and less than or equal to 100 kg at Screening. Consent to use contraception (both the subject and the subject's partner), for at least 70 days after the last dose of study medication starting on the day of informed consent, if the subject is a man capable of reproduction or a woman of childbearing potential. Has voluntarily consented, in writing, to participate in this study Has been thoroughly briefed on the conditions for participation in the study, and is willing and able to comply with all aspects of the protocol. Exclusion Criteria Subjects who meet any of the following criteria will be excluded from this study: Any history or complication of inflammatory arthritic disorder other than rheumatoid arthritis or Sjogren's syndrome. Meet Class 4 with the Steinbrocker functional classification. History or current clinical condition, or associated complications of malignant tumor, lymphoma, leukemia, or lymphoproliferative disease. Immunodeficiency or history of HIV infection Infection requiring hospitalization or intravenous administration of antibiotics within 4 weeks before the first dose of study treatment, or an infection requiring oral antibiotics within 2 weeks before the first dose of study treatment. History of tuberculosis or current complication of active tuberculosis. History of severe allergy (shock, or anaphylactoid symptoms). History of clinically important vascular edema, hematemesis, hemorrhagic stool, or hemoptysis. History of acute myocardial infarction, cerebral infarction, cerebral hemorrhage, or arteriosclerosis obliterans. History of clinically important vasculitis (such as mononeuritis multiplex). Tested positive for any of the following at Screening: human immunodeficiency virus (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 DNA (HBV DNA), hepatitis C virus antibody (HCV antibody), human T-lymphotrophic virus Type I antibody (HTLV-1 antibody), or syphilis. Any result other than negative in tuberculosis test (T-SPOT.TB Test or QuantiFERON TB Gold Test) at Screening. Findings indicating a history of tuberculosis on chest X-ray at Screening. Ineligible to participate in the study in the opinion of the investigator or sub investigator.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: E6011, 100 mg Arm<br>E6011 will be administered repeatedly, subcutaneously at Week 0, 1, 2, followed by every 2 weeks upto 10 weeks (treatment phase).100 mg group will receive E6011 subcutaneously, 1 ml. If a subject intends to continue administrations; the subject will receive a total of 20 subsequent biweekly administrations (40 weeks) at stable dose (Extension phase). | Drug: E6011<br> <br> |
| Experimental: E6011, 200 mg Arm<br>E6011 will be administered repeatedly, subcutaneously at Week 0, 1, 2, followed by every 2 weeks upto 10 weeks (treatment phase). 200 mg group will receive E6011 subcutaneously, 1 ml each at two sites. If a subject intends to continue administrations; the subject will receive a total of 20 subsequent biweekly administrations (40 weeks) at stable dose (Extension phase). | Drug: E6011<br> <br> |
| Experimental: E6011, 400 mg Arm<br>E6011 will be administered repeatedly, subcutaneously at Week 0, 1, 2, followed by every 2 weeks up to 10 weeks (treatment phase). 400 mg group will receive E6011 subcutaneously, 1 ml each at four sites or 2 ml each at two sites. If a subject intends to continue administrations, the subject will receive a total of 20 subsequent biweekly administrations (40 weeks) at stable dose (Extension Phase). | Drug: E6011<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |  | Up to 52 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Positive Anti-E6011 Antibodies Results |  | Up to 52 weeks | 
| Serum Concentrations of E6011 |  | At Week 0 (predose), Week 1, 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 (postdose) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid Arthritis, Japanese subjects