A Phase 1/2 Study of Repeated Intravenous E6011 Administration in Japanese Subjects With Crohn's Disease

Phase 1

Completed

Conditions: Crohn's Disease

Interventions: Drug: E6011 10 mg/kg
Drug: E6011 5 mg/kg
Drug: E6011 2 mg/kg
Drug: E6011 15 mg/kg

Registration Number: NCT02039063

Lead Sponsor: EA Pharma Co., Ltd.

Brief Summary: This study is a multicenter, open-label, uncontrolled, multiple ascending dose (MAD) study to evaluate mainly the safety and tolerability of 12-week repeated intravenous administration of E6011. A total of 24 subjects will enroll into four cohorts. Six subjects per cohort will receive repeated intravenous administration of E6011.

Detailed Description: This study consists of Screening Phase, Observation Phase, Treatment Phase, Extension Phase, and Follow-up Phase. Screening assessments will be performed between 42 to 2 days before study drug administration. Observation Phase assessments will be performed a day before or on a day of the initial administration to confirm the eligibility of subjects. The eligible subjects will receive the repeated intravenous administration of E6011. E6011 will be dissolved in physiological saline (nearly 100 mL) for approximately 30-minute infusion. During the Treatment Phase, for the first and second cohorts, E6011 will be administered every 2 weeks up to Week 10, a total of 6 times (with a double dose at Week 0). For the third and fourth cohorts, E6011 will be administered at Weeks 0, 1 and 2, then every 2 weeks up to Week 10, a total of 7 times. Under no safety concerns, Crohn's Disease Activity (CDAI) is less than 150 or a decrease in CDAI from the Observation Phase is greater than 70 and a subject intends to continue administrations, the subject will receive a total of 20 subsequent biweekly administrations (40 weeks) at stable dose (Extension Phase). Subjects will be hospitalized for 24 hours after the initial and second administrations for postdose monitoring and will have out-patient monitoring until 12 weeks after the initial administration. If hospitalization is difficult after the second administration, the subjects can be held at the hospital for 6 hours and then allowed to go home after confirmation of the safety. Subjects who roll over onto the Extension Phase will have continued monitoring until 52 weeks after the initial administration. When the subjects complete (Week 12 or Week 52) or discontinue the study, they will undergo an on-site follow-up 28 days after the study completion or discontinuation and an off-site follow-up or telephone interview 70 days after the final administration. The investigator will conduct full assessments of subjects safety next day of the second administration (24 hours after the second administration) to confirm presence of absence of study-related manifestations which may affect the study drug administration of next cohort. When the sponsor is informed of investigator's judgment on the sixth subject in each cohort, the appropriateness of next cohort will be judged based on the safety data available including the judgment of individual investigator on the next day of the second administration.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 28

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
3	E6011 10 mg/kg	E6011 10 mg/kg
2	E6011 5 mg/kg	E6011 5 mg/kg
1	E6011 2 mg/kg	E6011 2 mg/kg
4	E6011 15 mg/kg	E6011 15 mg/kg

Primary Outcome Measures

Name	Time	Method
Number of Participants With Clinically Significant Change in Laboratory Parameters	Baseline up to Week 52	Clinical laboratory parameters included biochemistry, hematology, urinalysis and other screening test. Number of participants with clinically significant abnormalities in laboratory parameters which were deemed clinically significant by the investigator were reported.
Number of Participants With Clinically Significant Change in Vital Sign Measurements	Baseline up to Week 52	Vital sign measurements included blood pressure (systolic and diastolic blood pressure) and pulse rate. Number of participants with clinically significant change in vital signs measurements which were deemed clinically significant by the investigator were reported.
Number of Participants With Abnormal Chest X-ray Findings	Baseline up to Week 52	Number of participants with abnormal chest X-ray findings were reported.
Number of Participants With Neurological Findings	Baseline up to Week 52	Number of participants with neurological findings were reported.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	Baseline up to Week 62 (70 days after last dose of study drug)	TEAEs was defined as adverse event (AEs) that emerged during the treatment, having been absent at pretreatment (Baseline) or re-emerged during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous. An AE was defined as any untoward medical occurrence in a participants or clinical study participant temporally associated with the use of study treatment, whether or not considered related to the study treatment. A SAE was defined as any untoward medical occurrence at any dose if it resulted in death or life-threatening AE or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions or was a congenital anomaly/birth defect.
Number of Participants With Treatment-emergent Clinically Significant Abnormal Electrocardiogram (ECG) Findings	Baseline up to Week 52	Number of participants with treatment-emergent clinically significant abnormal ECG findings which were deemed clinically significant by the investigator were reported.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Serum Anti-E6011 Antibody at Week 12 and 52	At Week 12 and Week 52	Number of participants with serum anti-E6011 antibody were reported.
Mean Trough Serum Concentration of E6011 at Week 12 and 52	Week 12: Pre-dose; Week 52: Pre-dose