Efficacy and Safety of DVC1-0101 for Intermittent Claudication Secondary to Peripheral Artery Disease: Study Protocol of a Randomized Phase IIb Trial

Abstract

1.1. Background: We have developed a new gene transfer vector based on nontransmissible recombinant Sendai virus expressing the human fibroblast growth factor-2 gene (DVC1-0101) to treat peripheral arterial disease. A phase I/IIa open-label four dose-escalation clinical trial for critical limb ischemia was completed. We concluded that DVC1-0101 is safe and well tolerated, and resulted in significant improvement of limb function. We present the protocol of the next phase of our study. 1.2. Methods: We plan to conduct a phase IIb clinical trial, which will be a randomized, placebo-controlled, parallel design, single-dose blinded and single center clinical trial in Japan. This study will enroll 60 patients diagnosed with PAD with intermittent claudication. Subjects who meet eligibility criteria will be randomized to receive a single dose of either placebo, 5 × 109 ciu/limb of DVC1-0101, or 1 × 109 ciu/limb of DVC1-0101 administered by direct intramuscular injection. The participation length in this trial for subjects will be approximately 12 months with nine visits. The primary endpoints are to evaluate the efficacy of DVC1-0101 versus placebo on peak walking time, and to evaluate the safety and tolerability of two dosage levels of DVC1-0101. The secondary endpoints are 1) to evaluate the effect of DVC1-0101 on claudication onset time, measured by a treadmill test and quality of life, measured using the Walking Impairment Questionnaire, 2) to determine the effect of DVC1-0101 on qualifying limb hemodynamics, and 3) to explore the pharmacodynamics of DVC1-0101 by evaluating biomarkers. 1.3. Discussion: The results of this trial will provide insights into the potential of DVC1-0101 for improving walking activities. The results will also help with the design of a possible phase III study.