Trial Outcomes & Findings for A Multicenter, Open-label Study for E7040 in Japanese Subjects With Hypervascular Tumor and Subjects With Arteriovenous Malformation (NCT NCT01677624)

Last Updated: 2016-02-22

Results Overview

Embolization performance was graded per 1 of 4 levels: (1) complete embolization, 100% disappearance of contrast enhancement in the target vessel as evaluated by post-embolization digital subtraction angiography; (2) intensive embolization, ≥80% disappearance; (3) moderate embolization, ≥50% and \<80% disappearance; (4) mild embolization, \<50% disappearance. Success rate was obtained by calculating the percentage of complete embolization and intensive embolization cases. Embolization performance evaluated by both the Imaging Evaluation Committee and by the Investigator or Subinvestigator.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

28 participants

Primary outcome timeframe

Day 1 (embolization) up to Day 30 after treatment

Results posted on

2016-02-22

Participant Flow

'Insufficient response' = Insuf Resp

Participant milestones

Participant milestones
Measure	Device E7040 An optimal dose and size (100 to 300 μm, 300 to 500 μm, 500 to 700 μm) of microsphere that best matches the pathology (i.e., vascular target, vessel size, and target lesion) and the extent of embolization were carefully selected.
Overall Study STARTED	28
Overall Study COMPLETED	27
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Device E7040 An optimal dose and size (100 to 300 μm, 300 to 500 μm, 500 to 700 μm) of microsphere that best matches the pathology (i.e., vascular target, vessel size, and target lesion) and the extent of embolization were carefully selected.
Overall Study Insuf Resp: intra-articular hemorrhage	1

Baseline Characteristics

A Multicenter, Open-label Study for E7040 in Japanese Subjects With Hypervascular Tumor and Subjects With Arteriovenous Malformation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Device E7040 n=28 Participants An optimal dose and size (100 to 300 μm, 300 to 500 μm, 500 to 700 μm) of microsphere that best matches the pathology (i.e., vascular target, vessel size, and target lesion) and the extent of embolization were carefully selected.
Age, Continuous	54.6 Years STANDARD_DEVIATION 12.87 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 (embolization) up to Day 30 after treatment

Population: The analysis was performed using Full Analysis Set defined as all participants who received embolization therapy with E7040 and had at least one evaluable efficacy data after the procedure.

Outcome measures

Outcome measures
Measure	Device E7040 n=28 Participants An optimal dose and size (100 to 300 μm, 300 to 500 μm, 500 to 700 μm) of microsphere that best matches the pathology (i.e., vascular target, vessel size, and target lesion) and the extent of embolization were carefully selected.
Success Rate of Embolization in the Target Vessel Imaging Evaluation Committee	100 Percentage of participants Interval 87.6 to 100.0
Success Rate of Embolization in the Target Vessel Investigator or Subinvestigator	96.4 Percentage of participants Interval 81.6 to 100.0

SECONDARY outcome

Timeframe: Day 1 (embolization) up to Day 30 after treatment

Operability and usability were evaluated by the Investigator on the basis of the sense of resistance when E7040 was injected, and how smoothly the microspheres could pass through the catheter. The evaluation criteria are very easy to use, easy to use, difficult to use, very difficult to use. Success rate was obtained by calculating the percentage of very easy to use and easy to use cases.

Outcome measures

Outcome measures
Measure	Device E7040 n=28 Participants An optimal dose and size (100 to 300 μm, 300 to 500 μm, 500 to 700 μm) of microsphere that best matches the pathology (i.e., vascular target, vessel size, and target lesion) and the extent of embolization were carefully selected.
Success Rate for Operability of Embolization	100 percentage of participants Interval 87.6 to 100.0

Adverse Events

Device E7040

Serious events: 2 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Device E7040 n=28 participants at risk An optimal dose and size (100 to 300 μm, 300 to 500 μm, 500 to 700 μm) of microsphere that best matches the pathology (i.e., vascular target, vessel size, and target lesion) and the extent of embolization were carefully selected.
Hepatobiliary disorders cholangitis	3.6% 1/28 • Adverse Events (AEs) were collected from the time of the procedure up to 30 days post procedure (if a surgery or local therapy was performed for the lesions where embolization was applied, AEs were collected up to that point). The analysis was performed using the Safety Analysis Set defined as all participants who received the embolization therapy with E7040 and had at least 1 evaluable safety data after the procedure.
Hepatobiliary disorders hepatic failure	3.6% 1/28 • Adverse Events (AEs) were collected from the time of the procedure up to 30 days post procedure (if a surgery or local therapy was performed for the lesions where embolization was applied, AEs were collected up to that point). The analysis was performed using the Safety Analysis Set defined as all participants who received the embolization therapy with E7040 and had at least 1 evaluable safety data after the procedure.

Other adverse events

Other adverse events
Measure	Device E7040 n=28 participants at risk An optimal dose and size (100 to 300 μm, 300 to 500 μm, 500 to 700 μm) of microsphere that best matches the pathology (i.e., vascular target, vessel size, and target lesion) and the extent of embolization were carefully selected.
Injury, poisoning and procedural complications Post embolisation syndrome	78.6% 22/28 • Adverse Events (AEs) were collected from the time of the procedure up to 30 days post procedure (if a surgery or local therapy was performed for the lesions where embolization was applied, AEs were collected up to that point). The analysis was performed using the Safety Analysis Set defined as all participants who received the embolization therapy with E7040 and had at least 1 evaluable safety data after the procedure.
Investigations Lymphocyte count decreased	32.1% 9/28 • Adverse Events (AEs) were collected from the time of the procedure up to 30 days post procedure (if a surgery or local therapy was performed for the lesions where embolization was applied, AEs were collected up to that point). The analysis was performed using the Safety Analysis Set defined as all participants who received the embolization therapy with E7040 and had at least 1 evaluable safety data after the procedure.
Investigations Aspartate aminotransferase increased	25.0% 7/28 • Adverse Events (AEs) were collected from the time of the procedure up to 30 days post procedure (if a surgery or local therapy was performed for the lesions where embolization was applied, AEs were collected up to that point). The analysis was performed using the Safety Analysis Set defined as all participants who received the embolization therapy with E7040 and had at least 1 evaluable safety data after the procedure.
Investigations Alanine aminotransferase increased	17.9% 5/28 • Adverse Events (AEs) were collected from the time of the procedure up to 30 days post procedure (if a surgery or local therapy was performed for the lesions where embolization was applied, AEs were collected up to that point). The analysis was performed using the Safety Analysis Set defined as all participants who received the embolization therapy with E7040 and had at least 1 evaluable safety data after the procedure.
Investigations Blood bilirubin increased	10.7% 3/28 • Adverse Events (AEs) were collected from the time of the procedure up to 30 days post procedure (if a surgery or local therapy was performed for the lesions where embolization was applied, AEs were collected up to that point). The analysis was performed using the Safety Analysis Set defined as all participants who received the embolization therapy with E7040 and had at least 1 evaluable safety data after the procedure.
Investigations Blood creatinine increased	10.7% 3/28 • Adverse Events (AEs) were collected from the time of the procedure up to 30 days post procedure (if a surgery or local therapy was performed for the lesions where embolization was applied, AEs were collected up to that point). The analysis was performed using the Safety Analysis Set defined as all participants who received the embolization therapy with E7040 and had at least 1 evaluable safety data after the procedure.
Investigations Blood pressure increased	10.7% 3/28 • Adverse Events (AEs) were collected from the time of the procedure up to 30 days post procedure (if a surgery or local therapy was performed for the lesions where embolization was applied, AEs were collected up to that point). The analysis was performed using the Safety Analysis Set defined as all participants who received the embolization therapy with E7040 and had at least 1 evaluable safety data after the procedure.
Investigations Blood urea increased	10.7% 3/28 • Adverse Events (AEs) were collected from the time of the procedure up to 30 days post procedure (if a surgery or local therapy was performed for the lesions where embolization was applied, AEs were collected up to that point). The analysis was performed using the Safety Analysis Set defined as all participants who received the embolization therapy with E7040 and had at least 1 evaluable safety data after the procedure.
Investigations C-reactive protein increased	10.7% 3/28 • Adverse Events (AEs) were collected from the time of the procedure up to 30 days post procedure (if a surgery or local therapy was performed for the lesions where embolization was applied, AEs were collected up to that point). The analysis was performed using the Safety Analysis Set defined as all participants who received the embolization therapy with E7040 and had at least 1 evaluable safety data after the procedure.
Investigations Blood urine present	10.7% 3/28 • Adverse Events (AEs) were collected from the time of the procedure up to 30 days post procedure (if a surgery or local therapy was performed for the lesions where embolization was applied, AEs were collected up to that point). The analysis was performed using the Safety Analysis Set defined as all participants who received the embolization therapy with E7040 and had at least 1 evaluable safety data after the procedure.
Investigations Protein urine present	10.7% 3/28 • Adverse Events (AEs) were collected from the time of the procedure up to 30 days post procedure (if a surgery or local therapy was performed for the lesions where embolization was applied, AEs were collected up to that point). The analysis was performed using the Safety Analysis Set defined as all participants who received the embolization therapy with E7040 and had at least 1 evaluable safety data after the procedure.
Investigations Blood alkaline phosphatase increased	10.7% 3/28 • Adverse Events (AEs) were collected from the time of the procedure up to 30 days post procedure (if a surgery or local therapy was performed for the lesions where embolization was applied, AEs were collected up to that point). The analysis was performed using the Safety Analysis Set defined as all participants who received the embolization therapy with E7040 and had at least 1 evaluable safety data after the procedure.
Investigations Blood albumin decreased	7.1% 2/28 • Adverse Events (AEs) were collected from the time of the procedure up to 30 days post procedure (if a surgery or local therapy was performed for the lesions where embolization was applied, AEs were collected up to that point). The analysis was performed using the Safety Analysis Set defined as all participants who received the embolization therapy with E7040 and had at least 1 evaluable safety data after the procedure.
Investigations Blood glucose increased	7.1% 2/28 • Adverse Events (AEs) were collected from the time of the procedure up to 30 days post procedure (if a surgery or local therapy was performed for the lesions where embolization was applied, AEs were collected up to that point). The analysis was performed using the Safety Analysis Set defined as all participants who received the embolization therapy with E7040 and had at least 1 evaluable safety data after the procedure.
Investigations Blood lactate dehydrogenase increased	7.1% 2/28 • Adverse Events (AEs) were collected from the time of the procedure up to 30 days post procedure (if a surgery or local therapy was performed for the lesions where embolization was applied, AEs were collected up to that point). The analysis was performed using the Safety Analysis Set defined as all participants who received the embolization therapy with E7040 and had at least 1 evaluable safety data after the procedure.
Investigations White blood cell count increased	7.1% 2/28 • Adverse Events (AEs) were collected from the time of the procedure up to 30 days post procedure (if a surgery or local therapy was performed for the lesions where embolization was applied, AEs were collected up to that point). The analysis was performed using the Safety Analysis Set defined as all participants who received the embolization therapy with E7040 and had at least 1 evaluable safety data after the procedure.
Gastrointestinal disorders Constipation	28.6% 8/28 • Adverse Events (AEs) were collected from the time of the procedure up to 30 days post procedure (if a surgery or local therapy was performed for the lesions where embolization was applied, AEs were collected up to that point). The analysis was performed using the Safety Analysis Set defined as all participants who received the embolization therapy with E7040 and had at least 1 evaluable safety data after the procedure.
Gastrointestinal disorders Nausea	21.4% 6/28 • Adverse Events (AEs) were collected from the time of the procedure up to 30 days post procedure (if a surgery or local therapy was performed for the lesions where embolization was applied, AEs were collected up to that point). The analysis was performed using the Safety Analysis Set defined as all participants who received the embolization therapy with E7040 and had at least 1 evaluable safety data after the procedure.
Gastrointestinal disorders Vomiting	21.4% 6/28 • Adverse Events (AEs) were collected from the time of the procedure up to 30 days post procedure (if a surgery or local therapy was performed for the lesions where embolization was applied, AEs were collected up to that point). The analysis was performed using the Safety Analysis Set defined as all participants who received the embolization therapy with E7040 and had at least 1 evaluable safety data after the procedure.
Gastrointestinal disorders Abdominal pain	10.7% 3/28 • Adverse Events (AEs) were collected from the time of the procedure up to 30 days post procedure (if a surgery or local therapy was performed for the lesions where embolization was applied, AEs were collected up to that point). The analysis was performed using the Safety Analysis Set defined as all participants who received the embolization therapy with E7040 and had at least 1 evaluable safety data after the procedure.
Musculoskeletal and connective tissue disorders Back pain	21.4% 6/28 • Adverse Events (AEs) were collected from the time of the procedure up to 30 days post procedure (if a surgery or local therapy was performed for the lesions where embolization was applied, AEs were collected up to that point). The analysis was performed using the Safety Analysis Set defined as all participants who received the embolization therapy with E7040 and had at least 1 evaluable safety data after the procedure.
Metabolism and nutrition disorders Decreased appetite	17.9% 5/28 • Adverse Events (AEs) were collected from the time of the procedure up to 30 days post procedure (if a surgery or local therapy was performed for the lesions where embolization was applied, AEs were collected up to that point). The analysis was performed using the Safety Analysis Set defined as all participants who received the embolization therapy with E7040 and had at least 1 evaluable safety data after the procedure.
Metabolism and nutrition disorders Hypocalcaemia	7.1% 2/28 • Adverse Events (AEs) were collected from the time of the procedure up to 30 days post procedure (if a surgery or local therapy was performed for the lesions where embolization was applied, AEs were collected up to that point). The analysis was performed using the Safety Analysis Set defined as all participants who received the embolization therapy with E7040 and had at least 1 evaluable safety data after the procedure.
Hepatobiliary disorders Hepatic function abnormal	7.1% 2/28 • Adverse Events (AEs) were collected from the time of the procedure up to 30 days post procedure (if a surgery or local therapy was performed for the lesions where embolization was applied, AEs were collected up to that point). The analysis was performed using the Safety Analysis Set defined as all participants who received the embolization therapy with E7040 and had at least 1 evaluable safety data after the procedure.
Nervous system disorders Headache	10.7% 3/28 • Adverse Events (AEs) were collected from the time of the procedure up to 30 days post procedure (if a surgery or local therapy was performed for the lesions where embolization was applied, AEs were collected up to that point). The analysis was performed using the Safety Analysis Set defined as all participants who received the embolization therapy with E7040 and had at least 1 evaluable safety data after the procedure.
Nervous system disorders Dizziness	7.1% 2/28 • Adverse Events (AEs) were collected from the time of the procedure up to 30 days post procedure (if a surgery or local therapy was performed for the lesions where embolization was applied, AEs were collected up to that point). The analysis was performed using the Safety Analysis Set defined as all participants who received the embolization therapy with E7040 and had at least 1 evaluable safety data after the procedure.
Reproductive system and breast disorders Pelvic pain	14.3% 4/28 • Adverse Events (AEs) were collected from the time of the procedure up to 30 days post procedure (if a surgery or local therapy was performed for the lesions where embolization was applied, AEs were collected up to that point). The analysis was performed using the Safety Analysis Set defined as all participants who received the embolization therapy with E7040 and had at least 1 evaluable safety data after the procedure.
General disorders Pyrexia	10.7% 3/28 • Adverse Events (AEs) were collected from the time of the procedure up to 30 days post procedure (if a surgery or local therapy was performed for the lesions where embolization was applied, AEs were collected up to that point). The analysis was performed using the Safety Analysis Set defined as all participants who received the embolization therapy with E7040 and had at least 1 evaluable safety data after the procedure.
Blood and lymphatic system disorders Anaemia	10.7% 3/28 • Adverse Events (AEs) were collected from the time of the procedure up to 30 days post procedure (if a surgery or local therapy was performed for the lesions where embolization was applied, AEs were collected up to that point). The analysis was performed using the Safety Analysis Set defined as all participants who received the embolization therapy with E7040 and had at least 1 evaluable safety data after the procedure.

Additional Information

Shin Maeda

Eisai Co., Ltd.

Phone: +81-3-3817-5252

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER