title: Design of the Del-1 for therapeutic angiogenesis trial (DELTA-1), a phase II multicenter, double-blind, placebo-controlled trial of VLTS-589 in subjects with intermittent claudication secondary to peripheral arterial disease.
abstract: The objective of this phase II investigation is to assess the safety and efficacy of a plasmid mediated approach to induce angiogenesis/arteriogenesis with the angiomatrix protein Del-1 (developmentally regulated endothelial locus 1), in subjects with intermittent claudication (IC) secondary to peripheral arterial disease (PAD). VLTS-589 is an investigational nonviral therapeutic comprising a plasmid-expressing Del-1 formulated with poloxamer 188 (facilitating agent). One hundred subjects with bilateral PAD and IC will be randomized after careful screening to bilateral intramuscular delivery of VLTS-589 or placebo. A total of 84 mg of plasmid or placebo will be delivered as 42 intramuscular injections (2 ml per injection, 21 injections or 42 ml in each extremity of either plasmid or placebo) in both lower extremities. The subjects in the study will be followed at regular intervals for a year after study drug administration (days 30, 90, 180, and 365) with the primary endpoint being the safety and tolerability of VLTS-589 and change in peak walking time (PWT) at day 90. The secondary endpoints include percent and absolute change in resting ankle brachial Index, claudication onset time, and quality of life measured at various time points. DELTA-1 represents the largest plasmid-based gene transfer trial designed to test the efficacy of a Del-1 as a therapeutic approach in patients with IC caused by PAD. The novel aspects of the protocol include the usage of a Del-1 plasmid-polaxamer formulation to enhance gene transfer at doses that are an order of magnitude different than other comparable trials in a unique bilateral intramuscular dosing pattern to maximize transfection/clinical efficacy and general applicability to patients with PAD.
authors.affiliation: Section of Vascular Medicine, Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai School of Medicine, Box #1030, One Gustave Levy Place, New York, NY 10029, USA. sanjay.rajagopalan@mssm.edu
authors.forename: Sanjay
authors.initials: S
authors.lastname: Rajagopalan
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Olin
authors.forename: Stuart
authors.initials: S
authors.lastname: Young
authors.forename: Marlena
authors.initials: M
authors.lastname: Erikson
authors.forename: Paul M
authors.initials: PM
authors.lastname: Grossman
authors.forename: Farrell O
authors.initials: FO
authors.lastname: Mendelsohn
authors.forename: Judith G
authors.initials: JG
authors.lastname: Regensteiner
authors.forename: William R
authors.initials: WR
authors.lastname: Hiatt
authors.forename: Brian H
authors.initials: BH
authors.lastname: Annex
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000627:therapeutic use*; D015815:Cell Adhesion Molecules; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007383:Intermittent Claudication / Q000209:etiology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D016491:Peripheral Vascular Diseases / Q000150:complications / Q000628:therapy*; D010919:Placebos
chemical_list: D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; C491706:Edil3 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D010919:Placebos