Clinical trial NCT02960490: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: E6011
rheumatoid arthritis
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2016-11-09
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility 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 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

Primary outcomes:
measure: 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)
timeFrame: Week 12
Secondary outcomes:
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: Change From Baseline in Tender Joint Counts (TJC) at Each Visit Based on Last Observation Carried Forward (LOCF)
timeFrame: Core 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 and 72
measure: Change From Baseline in Swollen Joint Counts (SJC) at Each Visit Based on LOCF
timeFrame: Core 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 and 72
measure: Change From Baseline in Participant's Assessment of Pain Based on VAS Score at Each Visit Based on LOCF
timeFrame: Core 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 and 72
measure: Change From Baseline in Participant's Global Assessment of Disease Activity Based on VAS Score at Each Visit Based on LOCF
timeFrame: Core 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 and 72
measure: Change From Baseline in Physician's Global Assessment of Disease Activity Scale Based on VAS Score at Each Visit Based on LOCF
timeFrame: Core 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 and 72
measure: Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Each Visit Based on LOCF
timeFrame: Core 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 and 72
measure: Change From Baseline in C-reactive Protein (CRP) Values at Each Visit Based on LOCF
timeFrame: Core 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 and 72
measure: Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Values at Each Visit Based on LOCF
timeFrame: Core 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 and 72
measure: Change From Baseline in Disease Activity Score 28 (DAS28)-ESR Values at Each Visit Based on LOCF
timeFrame: Core 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 and 72
measure: Change From Baseline in DAS28-CRP Values at Each Visit Based on LOCF
timeFrame: Core 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 and 72
measure: Change From Baseline in Simple Disease Activity Index (SDAI) Values at Each Visit Based on LOCF
timeFrame: Core 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 and 72
measure: Change From Baseline in Clinical Disease Activity Index (CDAI) Values at Each Visit Based on LOCF
timeFrame: Core 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 and 72
measure: Number of Participants With a European League Against Rheumatism (EULAR) Good, Moderate or No Response Using DAS28-ESR at Each Visit Based on NRI
timeFrame: 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
measure: Number of Participants With a EULAR Good, Moderate or No Response Using DAS28-CRP at Each Visit Based on NRI
timeFrame: 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
measure: Percentage of Participants Who Achieved SDAI Remission at Each Visit Based on NRI
timeFrame: 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
measure: Percentage of Participants Who Achieved CDAI Remission at Each Visit Based on NRI
timeFrame: 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
measure: Percentage of Participants Who Achieved Boolean Remission at Each Visit Based on NRI
timeFrame: 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
Other outcomes:
Locations:
city: Yotsukaido
country: Japan
facility: Eisai Trial Site #1
state: Chiba
city: Matsuyama
country: Japan
facility: Eisai Trial Site #1
state: Ehime
city: Kitakyushu
country: Japan
facility: Eisai Trial Site #1
state: Fukuoka
city: Takasaki
country: Japan
facility: Eisai Trial Site #1
state: Gunma
city: Takasaki
country: Japan
facility: Eisai Trial Site #2
state: Gunma
city: Asahikawa
country: Japan
facility: Eisai Trial Site #1
state: Hokkaido
city: Sapporo
country: Japan
facility: Eisai Trial Site #1
state: Hokkaido
city: Sapporo
country: Japan
facility: Eisai Trial Site #2
state: Hokkaido
city: Sapporo
country: Japan
facility: Eisai Trial Site #3
state: Hokkaido
city: Kato
country: Japan
facility: Eisai Trial Site #1
state: Hyogo
city: Ono
country: Japan
facility: Eisai Trial Site #1
state: Hyogo
city: Tsukuba
country: Japan
facility: Eisai Trial Site #1
state: Ibaraki
city: Sagamihara
country: Japan
facility: Eisai Trial Site #1
state: Kanagawa
city: Yokohama
country: Japan
facility: Eisai Trial Site #1
state: Kanagawa
city: Sasebo
country: Japan
facility: Eisai Trial Site #1
state: Nagasaki
city: Tomigusuku
country: Japan
facility: Eisai Trial Site #1
state: Okinawa
city: Kawachinagano
country: Japan
facility: Eisai Trial Site #1
state: Osaka
city: Kawagoe
country: Japan
facility: Eisai Trial Site #1
state: Saitama
city: Kawaguchi
country: Japan
facility: Eisai Trial Site #1
state: Saitama
city: Tokorozawa
country: Japan
facility: Eisai Trial Site #1
state: Saitama
city: Hamamatsu
country: Japan
facility: Eisai Trial Site #1
state: Shizuoka
city: Shimotsuke
country: Japan
facility: Eisai Trial Site #1
state: Tochigi
city: Chuo
country: Japan
facility: Eisai Trial Site #1
state: Tokyo
city: Fuchu
country: Japan
facility: Eisai Trial Site #1
state: Tokyo
city: Meguro-ku
country: Japan
facility: Eisai Trial Site #1
state: Tokyo
city: Ota
country: Japan
facility: Eisai Trial Site #1
state: Tokyo
city: Setagaya
country: Japan
facility: Eisai Trial Site #1
state: Tokyo
city: Shinjuku
country: Japan
facility: Eisai Trial Site #1
state: Tokyo
city: Shinjuku
country: Japan
facility: Eisai Trial Site #2
state: Tokyo
city: Takaoka
country: Japan
facility: Eisai Trial Site #1
state: Toyama
city: Chiba
country: Japan
facility: Eisai Trial Site #1
city: Fukui
country: Japan
facility: Eisai Trial Site #1
city: Fukuoka
country: Japan
facility: Eisai Trial Site #2
city: Fukuoka
country: Japan
facility: Eisai Trial Site #3
city: Fukuoka
country: Japan
facility: Eisai Trial Site #4
city: Fukuoka
country: Japan
facility: Eisai Trial Site #5
city: Hiroshima
country: Japan
facility: Eisai Trial Site #1
city: Kagoshima
country: Japan
facility: Eisai Trial Site #1
city: Kochi
country: Japan
facility: Eisai Trial Site #1
city: Kyoto
country: Japan
facility: Eisai Trial Site #1
city: Nagasaki
country: Japan
facility: Eisai Trial Site #1
city: Nagasaki
country: Japan
facility: Eisai Trial Site #2
city: Nagasaki
country: Japan
facility: Eisai Trial Site #3
city: Oita
country: Japan
facility: Eisai Trial Site #1
city: Toyama
country: Japan
facility: Eisai Trial Site #1
Study officials:
References: