Safety of a non-viral plasmid-encoding dual isoforms of hepatocyte growth factor in critical limb ischemia patients: A phase i study

T. D. Henry; A. T. Hirsch; J. Goldman; Y. L. Wang; D. L. Lips; W. D. McMillan; S. Duval; T. A. Biggs; H. H. Keo

doi:10.1038/gt.2011.21

Safety of a non-viral plasmid-encoding dual isoforms of hepatocyte growth factor in critical limb ischemia patients: A phase i study

T. D. Henry, A. T. Hirsch, J. Goldman, Y. L. Wang, D. L. Lips, W. D. McMillan, S. Duval, T. A. Biggs, H. H. Keo

Medicine - Cardiology Division

Research output: Contribution to journal › Article › peer-review

66 Scopus citations

Abstract

We aimed to evaluate in a phase I dose-escalation study, the safety of intramuscular injections of a novel non-viral plasmid DNA expressing two isoforms of human hepatocyte growth factor (HGF) (VM202) in patients with critical limb ischemia (CLI). In total, 12 patients with CLI and unsuitable for revascularization were consecutively assigned to increasing doses (2 to 16 mg) of VM202 administered into the ischemic calf muscle at days 1 and 15. Patients were evaluated for safety and tolerability, changes in ankle-and toe brachial index (ABI and TBI), and pain severity score using a visual analog scale (VAS) throughout a 12-month follow-up period. Median age was 72 years and 53% of the patients were male. VM202 was safe and well tolerated with no death during the 12-month follow-up. Median ABI and TBI significantly increased from 0.35 to 0.52 (P0.005) and from 0.15 to 0.24 (P0.01) at 12 months follow-up. Median VAS decreased from 57.5 to 16.0 mm at 6 months follow-up (P0.03). In this first human clinical trial, VM202, which expresses two isoforms of human HGF, appear to be safe and well tolerated with encouraging clinical results and thus supports the performance of a phase II randomized controlled trial.

Original language	English (US)
Pages (from-to)	788-794
Number of pages	7
Journal	Gene therapy
Volume	18
Issue number	8
DOIs	https://doi.org/10.1038/gt.2011.21
State	Published - Aug 2011

Bibliographical note

Funding Information:
We gratefully acknowledge the dedicated collaboration with Emile R Mohler III, MD, Director of Vascular Medicine, University of Pennsylvania Health System and Tracie C Collins, MD, MPH, Associate Professor, Department of Medicine, University of Minnesota, who are members of the DSMB. This study was funded by the ViroMed Co., Ltd, Seoul, Korea and was supported by grants from the Korean Ministry of Knowledge Economy (grant no. 10031644). We retain the sole responsibility for the data, statistical analysis and manuscript.

Keywords

angiogenesis-inducing agent
hepatocyte growth factor
peripheral vascular disease
two isoforms

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/gt.2011.21

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title = "Safety of a non-viral plasmid-encoding dual isoforms of hepatocyte growth factor in critical limb ischemia patients: A phase i study",

abstract = "We aimed to evaluate in a phase I dose-escalation study, the safety of intramuscular injections of a novel non-viral plasmid DNA expressing two isoforms of human hepatocyte growth factor (HGF) (VM202) in patients with critical limb ischemia (CLI). In total, 12 patients with CLI and unsuitable for revascularization were consecutively assigned to increasing doses (2 to 16 mg) of VM202 administered into the ischemic calf muscle at days 1 and 15. Patients were evaluated for safety and tolerability, changes in ankle-and toe brachial index (ABI and TBI), and pain severity score using a visual analog scale (VAS) throughout a 12-month follow-up period. Median age was 72 years and 53% of the patients were male. VM202 was safe and well tolerated with no death during the 12-month follow-up. Median ABI and TBI significantly increased from 0.35 to 0.52 (P0.005) and from 0.15 to 0.24 (P0.01) at 12 months follow-up. Median VAS decreased from 57.5 to 16.0 mm at 6 months follow-up (P0.03). In this first human clinical trial, VM202, which expresses two isoforms of human HGF, appear to be safe and well tolerated with encouraging clinical results and thus supports the performance of a phase II randomized controlled trial.",

keywords = "angiogenesis-inducing agent, hepatocyte growth factor, peripheral vascular disease, two isoforms",

author = "Henry, {T. D.} and Hirsch, {A. T.} and J. Goldman and Wang, {Y. L.} and Lips, {D. L.} and McMillan, {W. D.} and S. Duval and Biggs, {T. A.} and Keo, {H. H.}",

note = "Funding Information: We gratefully acknowledge the dedicated collaboration with Emile R Mohler III, MD, Director of Vascular Medicine, University of Pennsylvania Health System and Tracie C Collins, MD, MPH, Associate Professor, Department of Medicine, University of Minnesota, who are members of the DSMB. This study was funded by the ViroMed Co., Ltd, Seoul, Korea and was supported by grants from the Korean Ministry of Knowledge Economy (grant no. 10031644). We retain the sole responsibility for the data, statistical analysis and manuscript.",

year = "2011",

month = aug,

doi = "10.1038/gt.2011.21",

language = "English (US)",

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AU - Henry, T. D.

AU - Hirsch, A. T.

AU - Goldman, J.

AU - Wang, Y. L.

AU - Lips, D. L.

AU - McMillan, W. D.

AU - Duval, S.

AU - Biggs, T. A.

AU - Keo, H. H.

N1 - Funding Information: We gratefully acknowledge the dedicated collaboration with Emile R Mohler III, MD, Director of Vascular Medicine, University of Pennsylvania Health System and Tracie C Collins, MD, MPH, Associate Professor, Department of Medicine, University of Minnesota, who are members of the DSMB. This study was funded by the ViroMed Co., Ltd, Seoul, Korea and was supported by grants from the Korean Ministry of Knowledge Economy (grant no. 10031644). We retain the sole responsibility for the data, statistical analysis and manuscript.

PY - 2011/8

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N2 - We aimed to evaluate in a phase I dose-escalation study, the safety of intramuscular injections of a novel non-viral plasmid DNA expressing two isoforms of human hepatocyte growth factor (HGF) (VM202) in patients with critical limb ischemia (CLI). In total, 12 patients with CLI and unsuitable for revascularization were consecutively assigned to increasing doses (2 to 16 mg) of VM202 administered into the ischemic calf muscle at days 1 and 15. Patients were evaluated for safety and tolerability, changes in ankle-and toe brachial index (ABI and TBI), and pain severity score using a visual analog scale (VAS) throughout a 12-month follow-up period. Median age was 72 years and 53% of the patients were male. VM202 was safe and well tolerated with no death during the 12-month follow-up. Median ABI and TBI significantly increased from 0.35 to 0.52 (P0.005) and from 0.15 to 0.24 (P0.01) at 12 months follow-up. Median VAS decreased from 57.5 to 16.0 mm at 6 months follow-up (P0.03). In this first human clinical trial, VM202, which expresses two isoforms of human HGF, appear to be safe and well tolerated with encouraging clinical results and thus supports the performance of a phase II randomized controlled trial.

AB - We aimed to evaluate in a phase I dose-escalation study, the safety of intramuscular injections of a novel non-viral plasmid DNA expressing two isoforms of human hepatocyte growth factor (HGF) (VM202) in patients with critical limb ischemia (CLI). In total, 12 patients with CLI and unsuitable for revascularization were consecutively assigned to increasing doses (2 to 16 mg) of VM202 administered into the ischemic calf muscle at days 1 and 15. Patients were evaluated for safety and tolerability, changes in ankle-and toe brachial index (ABI and TBI), and pain severity score using a visual analog scale (VAS) throughout a 12-month follow-up period. Median age was 72 years and 53% of the patients were male. VM202 was safe and well tolerated with no death during the 12-month follow-up. Median ABI and TBI significantly increased from 0.35 to 0.52 (P0.005) and from 0.15 to 0.24 (P0.01) at 12 months follow-up. Median VAS decreased from 57.5 to 16.0 mm at 6 months follow-up (P0.03). In this first human clinical trial, VM202, which expresses two isoforms of human HGF, appear to be safe and well tolerated with encouraging clinical results and thus supports the performance of a phase II randomized controlled trial.

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KW - hepatocyte growth factor

KW - peripheral vascular disease

KW - two isoforms

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Safety of a non-viral plasmid-encoding dual isoforms of hepatocyte growth factor in critical limb ischemia patients: A phase i study

Abstract

Bibliographical note

Keywords

UN SDGs

Publisher link

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