Safety and Efficacy Study of Ad2/Hypoxia Inducible Factor (HIF)-1α/VP16 Gene Transfer in Patients With Intermittent Claudication
Condition: Intermittent Claudication; Peripheral Vascular Disease; Atherosclerosis
MeSH terms: Atherosclerosis; Vascular Diseases; Intermittent Claudication; Peripheral Vascular Diseases; Peripheral Arterial Disease; Hypoxia
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this Phase 2 clinical research study is to examine the safety of an
      experimental gene transfer agent, Ad2/HIF-1α/VP16, and its ability to stimulate the growth of
      new blood vessels from existing blood vessels (a process called angiogenesis) in an attempt
      to improve the flow of blood in the legs of patients with peripheral arterial disease (PAD).

      Specifically, this study will enroll patients with severe intermittent claudication (IC)
      which is the stage of PAD in which a patient's walking ability is severely limited, causing
      pain in the legs upon exercise due to inadequate blood flow to the muscles of the lower
      limbs.
    

Detailed description: 
      This Phase 2 gene transfer study will look at whether different doses of Ad2/HIF-1α/VP16 can
      be tolerated safely by direct injection into the leg muscles where the blood flow is not
      sufficient to meet the oxygen demands of the leg muscles. The study will also assess whether
      patients who receive the investigational drug product are able to increase their maximal
      walking time using a standardized treadmill walking test.

      The study design is a randomized, double-blind, placebo-controlled, parallel group,
      multi-center, Phase 2 dose-selection study. Seventy-five patients will be enrolled into each
      of 4 study drug groups (3 groups of Ad2/HIF-1α/VP16 gene transfer and 1 placebo group) for a
      total of 300 patients overall. Three different doses of Ad2/HIF-1α/VP16 gene transfer will be
      studied. The dose range was previously tested in animals and in the Phase 1 human studies. A
      placebo group is included in the study to compare safety and efficacy of different doses of
      Ad2/HIF-1α/VP16 with placebo. Each patient will receive a single set of 20 injections (100 μL
      each) of gene transfer or placebo in one administration to each leg for a total of 40
      injections.
    

Intervention name(s): Ad2/HIF-1α/VP16; Ad2/HIF-1α/VP16; Ad2/HIF-1α/VP16; Saline (Placebo Control)
Intervention type(s): Biological; Biological; Biological; Other
Intervention description(s): a one time treatment of 20 IM injections of 0.01 ML each into each leg for a total of 40 injections; one time treatment of 20 IM injections of 0.01 ML each into each leg for a total of 40 injections.; a one time treatment of 20 IM injections of 0.01 ML each into each leg for a total of 40 injections.; a one time treatment of 20 IM injections of 0.01 ML each into each leg for a total of 40 injections.
Other intervention name(s): HIF-1alpha; HIF-1alpha; HIF-1alpha
Intervention MeSH terms: Etoposide; Etoposide phosphate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: leg pain; gene transfer; angiogenesis; Phase 2; Genzyme; peripheral arterial disease