Study of Hepatocyte Growth Factor (HGF) Via Plasmid Vector to Improve Perfusion in Critical Limb Ischemia Patients With Peripheral Ischemic Ulcers

This study has been completed.

Sponsor:

Information provided by:

AnGes

ClinicalTrials.gov Identifier:

NCT00189540

First received: September 12, 2005

Last updated: July 25, 2011

Last verified: July 2011

History of Changes

Results First Received: June 21, 2011

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Conditions:	Arterial Occlusive Disease Peripheral Vascular Disease Ischemia Ulcers
Interventions:	Genetic: HGF plasmid Genetic: Placebo

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Screening was up to 30 days

Reporting Groups

	Description
Active Group	4.0 mg AMG0001 via IM injections on days 0, 14, and 28
Placebo Group	Placebo (saline)via IM injections on days 0, 14, and 28

Participant Flow: Overall Study

	Active Group	Placebo Group
STARTED	21	6
COMPLETED	14	5
NOT COMPLETED	7	1
Withdrawal by Subject	3	0
Death	4	1

Baseline Characteristics

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Reporting Groups

	Description
Active Group	4.0 mg AMG0001 via IM injections on days 0, 14, and 28
Placebo Group	Placebo (saline)via IM injections on days 0, 14, and 28
Total	Total of all reporting groups

Baseline Measures

	Active Group	Placebo Group	Total
Number of Participants [units: participants]	21	6	27
Age [units: years] Mean ± Standard Deviation	75.7 ± 2.49	78.0 ± 1.86	76.2 ± 1.97
Gender [units: participants]
Female	8	4	12
Male	13	2	15

Outcome Measures

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1. Primary:

Wound Healing (Change in Total Wound Area of All Ischemic Ulcers) [ Time Frame: Baseline, Month 3, Month 6 ]

Measure Type	Primary
Measure Title	Wound Healing (Change in Total Wound Area of All Ischemic Ulcers)
Measure Description	Wound healing measured by change in mean total wound area of all ischemic ulcers at Month 3 and Month 6
Time Frame	Baseline, Month 3, Month 6
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Per protocol population - Efficacy Evaluable or EE

Reporting Groups

	Description
Active Group	4.0 mg AMG0001 via IM injections on days 0, 14, and 28
Placebo Group	Placebo (saline)via IM injections on days 0, 14, and 28

Measured Values

	Active Group	Placebo Group
Number of Participants Analyzed [units: participants]	16	5
Wound Healing (Change in Total Wound Area of All Ischemic Ulcers) [units: total wound area (cm^2)] Mean ± Standard Error
Baseline	5.75 ± 1.8134	12.600 ± 9.4435
Month 3	15.766 ± 6.8421	12.200 ± 8.7022
Month 6	16.375 ± 7.1336	12.700 ± 9.7190

Statistical Analysis 1 for Wound Healing (Change in Total Wound Area of All Ischemic Ulcers)

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.35

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Comparison made is the difference from baseline at Month 3.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

Statistical Analysis 2 for Wound Healing (Change in Total Wound Area of All Ischemic Ulcers)

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.17

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Comparison made is the difference from baseline at Month 6.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

2. Secondary:

Percentage of Participants Where All Ulcers Healed [ Time Frame: Month 3 and Month 6 ]

Measure Type	Secondary
Measure Title	Percentage of Participants Where All Ulcers Healed
Measure Description	This outcome is a percentage of participants where all of their baseline ulcers healed.
Time Frame	Month 3 and Month 6
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Per protocol population Efficacy Evaluable "EE"

Reporting Groups

	Description
Active Group	4.0 mg AMG0001 via IM injections on days 0, 14, and 28
Placebo Group	Placebo (saline)via IM injections on days 0, 14, and 28

Measured Values

	Active Group	Placebo Group
Number of Participants Analyzed [units: participants]	16	5
Percentage of Participants Where All Ulcers Healed [units: Percentage of Participants]
Month 3	6	0
Month 6	19	0
Month 12	31	0

Statistical Analysis 1 for Percentage of Participants Where All Ulcers Healed

Groups ^[1]	All groups
Method ^[2]	Fisher Exact
P Value ^[3]	0.55

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	The comparison of groups at Month 3
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

Statistical Analysis 2 for Percentage of Participants Where All Ulcers Healed

Groups ^[1]	All groups
Method ^[2]	Fisher Exact
P Value ^[3]	0.28

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	The comparison of groups at Month 6.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

3. Secondary:

Change in Pain at Rest as Measured on the Visual Analog Scale (VAS) [ Time Frame: Baseline, Month 3 and Month 6 ]

Measure Type	Secondary
Measure Title	Change in Pain at Rest as Measured on the Visual Analog Scale (VAS)
Measure Description	The mean VAS score where 0 = no pain; 10 = worst possible pain.
Time Frame	Baseline, Month 3 and Month 6
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Per protocol population or Efficacy Evaluable "EE"

Reporting Groups

	Description
Active Group	4.0 mg AMG0001 via IM injections on days 0, 14, and 28
Placebo Group	Placebo (saline)via IM injections on days 0, 14, and 28

Measured Values

	Active Group	Placebo Group
Number of Participants Analyzed [units: participants]	16	5
Change in Pain at Rest as Measured on the Visual Analog Scale (VAS) [units: cm] Mean ± Standard Error
Baseline	5.31 ± 0.60	6.04 ± 1.20
Month 3	4.26 ± 0.92	6.52 ± 1.5
Month 6	3.40 ± 0.99	6.66 ± 1.3

Statistical Analysis 1 for Change in Pain at Rest as Measured on the Visual Analog Scale (VAS)

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.2

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Comparison between groups at Month 3
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

Statistical Analysis 2 for Change in Pain at Rest as Measured on the Visual Analog Scale (VAS)

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.04

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Comparison between groups at Month 6
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

4. Secondary:

Number of Subjects Who Undergo a Major Amputation [ Time Frame: Month 3 and Month 6 ]

Measure Type	Secondary
Measure Title	Number of Subjects Who Undergo a Major Amputation
Measure Description	No text entered.
Time Frame	Month 3 and Month 6
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Active Group	4.0 mg AMG0001 via IM injections on days 0, 14, and 28
Placebo Group	Placebo (saline)via IM injections on days 0, 14, and 28

Measured Values

	Active Group	Placebo Group
Number of Participants Analyzed [units: participants]	16	5
Number of Subjects Who Undergo a Major Amputation [units: participants]
3 months	3	0
6 months	3	0

Statistical Analysis 1 for Number of Subjects Who Undergo a Major Amputation

Groups ^[1]	All groups
Method ^[2]	Fisher Exact
P Value ^[3]	1.00

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

5. Secondary:

Change in Hemodynamic Measurements - Mean Change in Ankle Brachial Index (ABI) [ Time Frame: Baseline, Month 3, Month 6 ]

Measure Type	Secondary
Measure Title	Change in Hemodynamic Measurements - Mean Change in Ankle Brachial Index (ABI)
Measure Description	No text entered.
Time Frame	Baseline, Month 3, Month 6
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Population is per protocol - Efficacy Evaluable (EE)

Reporting Groups

	Description
Active Group	4.0 mg AMG0001 via IM injections on days 0, 14, and 28
Placebo Group	Placebo (saline)via IM injections on days 0, 14, and 28

Measured Values

	Active Group	Placebo Group
Number of Participants Analyzed [units: participants]	16	5
Change in Hemodynamic Measurements - Mean Change in Ankle Brachial Index (ABI) [units: mm Hg / mm Hg] Mean ± Standard Error
Baseline	0.492 ± 0.0662	0.430 ± 0.0957
Month 3	0.476 ± 0.0657	0.448 ± 0.1248
Month 6	0.472 ± 0.0846	0.303 ± 0.1481

Statistical Analysis 1 for Change in Hemodynamic Measurements - Mean Change in Ankle Brachial Index (ABI)

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.77

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Comparison at Month 3
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

Statistical Analysis 2 for Change in Hemodynamic Measurements - Mean Change in Ankle Brachial Index (ABI)

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.45

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Comparison at Month 6
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

6. Secondary:

Change in Hemodynamic Measurements - Mean Change in Toe Brachial Index (TBI) [ Time Frame: Baseline, Month 3, Month 6 ]

Measure Type	Secondary
Measure Title	Change in Hemodynamic Measurements - Mean Change in Toe Brachial Index (TBI)
Measure Description	No text entered.
Time Frame	Baseline, Month 3, Month 6
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Population is per protocol - Efficacy Evaluable (EE)

Reporting Groups

	Description
Active Group	4.0 mg AMG0001 via IM injections on days 0, 14, and 28
Placebo Group	Placebo (saline)via IM injections on days 0, 14, and 28

Measured Values

	Active Group	Placebo Group
Number of Participants Analyzed [units: participants]	16	5
Change in Hemodynamic Measurements - Mean Change in Toe Brachial Index (TBI) [units: mm Hg / mm Hg] Mean ± Standard Error
Baseline	0.19 ± 0.04	0.28 ± 0.06
Month 3	0.22 ± 0.05	0.14 ± 0.06
Month 6	0.24 ± 0.06	0.11 ± 0.07

Statistical Analysis 1 for Change in Hemodynamic Measurements - Mean Change in Toe Brachial Index (TBI)

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.06

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Comparison between groups for mean TBI at Month 3 versus baseline.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

Statistical Analysis 2 for Change in Hemodynamic Measurements - Mean Change in Toe Brachial Index (TBI)

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.05

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Comparison between groups for mean TBI at Month 6 versus baseline.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Multi-center all inclusive initial publication planned. Any proposed publications must be submitted to the steering committee and sponsor thirty (30) days prior to publication submission.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: Director of Clinical Operations
Organization: AnGes
phone: 240-780-9031
e-mail: information@anges-mg.com

Publications of Results:

Powell RJ, Goodney P, Mendelsohn FO, Moen EK, Annex BH; HGF-0205 Trial Investigators. Safety and efficacy of patient specific intramuscular injection of HGF plasmid gene therapy on limb perfusion and wound healing in patients with ischemic lower extremity ulceration: results of the HGF-0205 trial. J Vasc Surg. 2010 Dec;52(6):1525-30.

Responsible Party:	Prannath Marrott, M.D., AnGes, Inc.
ClinicalTrials.gov Identifier:	NCT00189540 History of Changes
Other Study ID Numbers:	AG-CLI-0205
Study First Received:	September 12, 2005
Results First Received:	June 21, 2011
Last Updated:	July 25, 2011
Health Authority:	United States: Food and Drug Administration

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