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Gene Therapy using Intramuscular Administration of AMG0001 in Patients with Peripheral Arterial Disease (Gene Therapy using Intramuscular Administration of AMG0001 in Patients with Peripheral Arterial Disease)

Angiogenic Gene Therapy with HGF Gene (Angiogenic Gene Therapy with HGF Gene)

6

Subject ID Target disease name Total dose (Number of doses) Age Sex medical history GM1401-01-001 Buerger disease 8mg (2) 48 Female None GM1401-02-001 Buerger disease 12mg (3) 42 Male None GM1401-03-001 Buerger disease 12mg (3) 70 Male None GM1401-04-001 Atherosclerosis obliterans 12mg (3) 80 Male Yes GM1401-06-001 Atherosclerosis obliterans 8mg (2) 80 Male Yes GM1401-06-002 Buerger disease 12mg (3) 81 Male Yes

Example of informed consent: 8 Complete registration: 6 Not registered: 2 Test substance administration example: 6 Untreated sample: 2 Clinical study completed cases: 6(Number of doses Twice/ 2 Patients Number of doses3 times/4 Patients) Clinical study discontinued cases: 0 Followup survey completion example: 5 Examples of followup not completed: 1 Prognostic survey completion example: 3 Prognostic survey incomplete cases: 2

Subject ID: GM1401-01-001 Preferred Term: Back pain, Anxiety disorder Subject ID: GM1401-02-001 Preferred Term: Pain Subject ID: GM1401-03-001 Preferred Term: Rash, Gastric cancer, Anaemia, Myocardial rupture, Pneumonia aspiration, Shunt occlusion, Wound dehiscence, Gangrene, Osteonecrosis Subject ID: GM1401-04-001 Preferred Term: Arthralgia, Ligament sprain, Lower limb fracture, Cerebral infarction Subject ID: GM1401-06-002 Preferred Term: Gastrooesophageal reflux di

Primary endpoint Improvement rate of resting pain (VAS) or ulcer size (major axis x minor axis) after 12 weeks (or when discontinued)(FAS) The improvement rate of resting pain (VAS) or ulcer size (major axis x minor axis) after 12 weeks after discontinuation (7%) was 75.0%. Admitted. Secondary endpoint (1) Transition of improvement rate of resting pain (VAS) or ulcer size (major axis x minor axis) (FAS) The transition of improvement rate of resting pain (VAS) or ulcer size (major axis x minor axis) is shown below.The improvement rate after 8 weeks of the post observation period or 8 weeks after the test treatment period was 80.0%, and the improvement rate after 12 weeks of the post observation period or when discontinued was 75.0%.There was no significant change in the improvement rate after 8 weeks of the post observation period or 8 weeks after the study treatment period and 12 weeks after the post observation period or at the time of discontinuation. (3) Ulcer size (major axis x minor axis) (FAS) A list of changes in ulcer size by subject is shown below. The size of ulcer (major axis x minor axis) as the main evaluation target was 0 after 8 weeks of the post observation period or 8 weeks of the test treatment period, and was 0 after 12 weeks of the post observation period or until discontinuation. There was no improvement for other ulcers that were not the primary assessment. (4) ABI improvement rate(FAS) The improvement rate of ABI and the change of ABI by patient are shown below.Overall, improvement was observed in 1 out of 5 cases, but when limited to obstructive arteriosclerosis, 1 out of 2 cases showed improvement. (5) Fontaine classification(FAS) The fontaine classification by subject immediately before administration and 12 weeks after the observation period (or at the time of discontinuation) is shown below.There were no subjects whose Fontaine classification changed from 1 week after the preobservation period to 12 weeks after the postobservation period or at the time of discontinuation. (6) Frequency of painless patients(FAS) Subjects who no longer used analgesics after 2 weeks from the previous observation period to 12 weeks after the subsequent observation period or when discontinued are shown below.For subjects who used analgesics after 2 weeks of the preobservation period, one patient no longer needed the analgesics after 12 weeks or when discontinued.In addition, for subjects who did not use analgesics after 2 weeks of the preobservation period, no analgesics were continuously used after 12 weeks of the postobservation period or even when discontinued.

Nine adverse events occurred in 5 of 6 cases (83.3%) and adverse reactions occurred in 2 of 6 cases (33.3%) during the period from the study treatment period to the postobservation period. Serious adverse events occurred in 1 of 6 cases (16.7%). The improvement rate of the primary endpoint, resting pain (VAS) or ulcer size (major axis x minor axis) after 12 weeks after discontinuation (or discontinuation) was 75% (3 of 4 cases) More patients showed improvement.

Dec. 05, 2019

No

Not applicable

https://jrct.mhlw.go.jp/latest-detail/jRCTs053180162

Rakugi Hiromi

Osaka University Hospital

2-15 Yamadaoka, Suita, Osaka

rakugi@geriat.med.osaka-u.ac.jp

Shimamura Munehisa

Osaka University

2-2 Yamadaoka, Suita, Osaka

+81-6-6210-8359

shimamuu@cgt.med.osaka-u.ac.jp

Complete

Sept. 01, 2014

Interventional

single arm study

open(masking not used)

no treatment control/standard of care control

single assignment

other

1. Patients who personally give informed consent in writing
2. Patients aged 20 or older but younger than 85
3. Patients who have a stenosis or occlusion in superficial femoral artery, popliteal artery, or artery below the popliteal of the treated limb confirmed by MRA or CTA.
4. The mean ankle pressure is less than 70 mmHg or ABI is not more than 0.6 during the observation period. (However, this shall not apply in the case of Buerger's disease.)
5. Those who have the following clinical symptoms due to stenosis or occlusion.
Rest pain (Fontaine III ) VAS is at least 20mm during the observation period
Ulcer (Fontaine IV )
6. Patients in whom revascularization in the treated limb is difficult, or patients who are determined that the adaptation is not impossible but there are some risks in surgery
7. Patients showing no symptom of improvement in the treated limb despite the conduct of conventional medical treatment or intervention for more than two weeks in the observation period after obtaining informed consent. The conventional medical treatment or intervention needs to be continued more than two weeks before obtaining the informed consent.
8. Patients who agree to contraception by a sperm passage blocking method until the end of Week 12 of treatment after obtaining informed consent
9. Inpatient, outpatient allowed

1. Patients with a necrotized ulcer and/or an ulcer with exposed tendon or bone in the treated or non-treated limb
2. Patients in whom alcohol or drug dependence had been noted 90 days or less before obtaining informed consent
3. Patient with malignant tumor history or merger. Patients with no recurrence of breast cancer more than 10 years, and with no recurrence of all other tumor types before obtaining informed consent, may be enrolled in the clinical research. Patients must been completed the cancer screening tests as defined in the protocol.
4. Patient with serious cardiac, renal or hematological disease, but excluding plateau chronic maintenance dialysis patients.
5. Patients with HIV antigen or antibody positive
6. Patients who underwent revascularization or amputation in the treated or non-treated limb, excluding small incision, necrotomy or onychectomy etc.
7. Patients who underwent sympathectomy or sympathetic block 90 days or less before obtaining informed consent
8. Patients with an invasive infectious disease which is difficult to control with antibiotics
9. Patients with proliferative diabetic retinopathy of untreated or treatment-resistant, or patients with neovascularization-type age-related macular degeneration
10. Patients with diabetic neuropathy (diffuse symmetrical neuropathy)
11. Participation in another clinical trial 30 days or less before obtaining informed consent
12. Past history of gene therapy excluding AMG0001
13. Pregnant or breast-feeding women, women with suspected pregnancy, and women who desire to become pregnant during the clinical research
14. Patients who were judged to be unsuitable for the clinical research by the attending physician

Both

Peripheral Arterial Disease

An AMG0001 formulation (2.5 mg/ml, 2.1 ml/vial) will be prepared before use and administered to 8 sites with ischemia in the target limb, 0.5 mg of AMG0001 per site (total dose: 4.0 mg).

Pain at rest
ulcer

1. Efficacy
1) Pain at rest
2) Ulcer
3) ABI (ankle-brachial systolic pressure index)
4) Fontaine classification
5) Frequency of analgesics-free patients
2. Safety
Adverse events , Adverse reaction , Serious adverse events by referring to vital sings , physical examination , laboratory test , urine test , ECG .

+81-6-6210-8296

Jan. 04, 2019

none