UMIN-CTR Clinical Trial

Public title

Randomized, double-blind, placebo-controlled study of AMG0001(HGF plasmid) for patients with arteriosclerosis obliterans

Acronym

Randomized, double-blind, placebo-controlled study of AMG0001(HGF plasmid) for patients with arteriosclerosis obliterans

Scientific Title

Randomized, double-blind, placebo-controlled study of AMG0001(HGF plasmid) for patients with arteriosclerosis obliterans

Scientific Title:Acronym

Randomized, double-blind, placebo-controlled study of AMG0001(HGF plasmid) for patients with arteriosclerosis obliterans

Region

Japan

Condition

Arteriosclerosis obliterans

Classification by specialty

Cardiology

Vascular surgery

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

The superiority of the efficacy of AMG0001 for arteriosclerosis obliterans (ASO) over placebo will be determined using the ischemic ulcer improvement rate and resting pain improvement rate as major variables.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Developmental phase

Phase III

Primary outcomes

Improvement of pain at rest and ischemic ulcer

Key secondary outcomes

Time course of pain at rest and Ischemic ulcer
Ankle brachial index
Fontaine classification
Angiogenesis
Incidence of subjects without analgesic
Quality of life
Amputation of drug-administered leg
Adverse events
Investigations and vital signs
Serum HGF level
Serum anti-HGF antibody
Serum anti-Escherichia protein antibody
Serum anti-DNA antibody

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Double blind -all involved are blinded

Control

Placebo

Stratification

YES

Dynamic allocation

YES

Institution consideration

Institution is considered as adjustment factor in dynamic allocation.

Blocking

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

An AMG0001 formulation (2.5 mg/ml, 1.85 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).

Interventions/Control_2

A placebo, an injectable form externally indistinguishable from the AMG0001 formulation, will be prepared before use and administered to 8 sites in the same manner as the AMG0001 formulation.

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

40

years-old

<=

Age-upper limit

85

years-old

>

Gender

Male and Female

Key inclusion criteria

1. Patients who personally give informed consent in writing
2. Patients aged 40 or older but younger than 85
3. Fontaine III (resting pain) or IV (ischemic ulcer)
4. Patients in whom hemodynamic parameters meet both of the following criteria:
* ABPI at rest is not more than 0.6 during the observation period.
* The mean ankle pressure is less than 70 mmHg during the observation period.
5. Patients in whom revascularization in the treated limb is difficult
6. Patients in whom symptoms are not improved in the treated limbs despite the conduct of conventional medical treatment or intervention for 4 weeks or more
7. Patients who agree to contraception by a sperm passage blocking method until the end of Week 12 of treatment after giving informed consent

Key exclusion criteria

1. Patients with a necrotized ulcer and/or an ulcer with exposed tendon or bone
2. Patients in whom alcohol or drug dependence had been noted 90 days or less before informed consent was obtained or who had been treated for it
3. Past history of or complication with cancer
4. Patients with serious cardiac, hepatic, renal, or hematological disease
5. Patients with intercurrent hepatitis B or C, AIDS, or ATL
6. Patients who underwent revascularization or amputation (not necrotomy) 90 days or less before giving informed consent
7. Patients who underwent sympathectomy or sympathetic block 180 days or less before giving informed consent
8. Patients with an invasive infectious disease which is difficult to control with antibiotics
9. Patients with proliferating diabetic retinopathy (untreated or in the middle or late stage of proliferating retinopathy) or neovascularization-type age-related macular degeneration
10. Participation in another clinical trial 90 days or less before giving informed consent
11. Pregnant or breast-feeding women, women with suspected pregnancy, and women who desire to become pregnant during the trial
12. Past history of cell therapy
13. Past history of gene therapy
14. Blood sampling (or donation) of 200 ml or more, 30 days or less before giving informed consent, or 400 ml or more, 90 (120 in the case of women) days or less before giving informed consent

Target sample size

120

Name of lead principal investigator

1st name
Middle name
Last name	Hiroshi Shigematsu

Organization

Tokyo Medical University

Division name

Second Department of Surgery

Zip code

Address

6-7-1, nishi-shinjuku, Shinjuku-ku, Tokyo, Japan 160-0023

TEL

Email

Name of contact person

1st name
Middle name
Last name

Organization

Anges MG, Inc.

Division name

Regulatory affairs

Zip code

Address

5-20-14, shiba, Minato-ku, Tokyo, Japan 108-0014

TEL

Homepage URL

Email

Institute

Anges MG, Inc.

Institute

Department

Personal name

Organization

Anges MG, Inc.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

YES

Study ID_1

JapicCTI-050186

Org. issuing International ID_1

Japan Pharmaceutical Information Center

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2007

Year

06

Month

04

Day

URL releasing protocol

Publication of results

Published

URL related to results and publications

http://www.ncbi.nlm.nih.gov/pubmed/20393508

Number of participants that the trial has enrolled

Results

Analysis of efficacy was performed in 40 patients with critical limb ischemia (CLI).
The primary end point was the improvement of rest pain in patients without ulcers (Rutherford 4) or the reduction of ulcer size in patients with ulcer(s) (Rutherford 5).
The overall improvement rate of the primary end point was 70.4% (19/27) in HGF group and 30.8% (4/13) in placebo group, showing a significant difference (P=0.014). In Rutherford 5 patients, HGF achieved a significantly higher improvement rate (100% [11/11]) than placebo (40% [2/5]; P=0.018). HGF plasmid also improved QOL. There were no major safety problems. HGF gene therapy is safe and effective for CLI.

Gene Ther. 2010 Sep;17(9):1152-61. Epub 2010 Apr 15.

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2003

Year

11

Month

14

Day

Date of IRB

Anticipated trial start date

2004

Year

02

Month

01

Day

Last follow-up date

2008

Year

08

Month

01

Day

Date of closure to data entry

2008

Year

09

Month

01

Day

Date trial data considered complete

2008

Year

10

Month

01

Day

Date analysis concluded

2009

Year

03

Month

01

Day

Other related information

Registered date

2007

Year

06

Month

04

Day

Last modified on

2010

Year

10

Month

06

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000000877