Rationale and design of the granulocyte-macrophage colony stimulating factor in peripheral arterial disease (GPAD-3) study
Anurag Mehta, Kreton Mavromatis, Yi-An Ko, Steven C Rogers, Devinder S Dhindsa, Cydney Goodwin, Risha Patel, Mohammad A Martini, Mahadev Prasad, Ali Mokhtari, Iraj G Hesaroieh, Stephen C Frohwein, Michael H Kutner, Arash Harzand, Bryan J Wells, Yazan Duwayri, Olamide Alabi, Ravi R Rajani, Luke P Brewster, Edmund K Waller, Arshed A Quyyumi, Anurag Mehta, Kreton Mavromatis, Yi-An Ko, Steven C Rogers, Devinder S Dhindsa, Cydney Goodwin, Risha Patel, Mohammad A Martini, Mahadev Prasad, Ali Mokhtari, Iraj G Hesaroieh, Stephen C Frohwein, Michael H Kutner, Arash Harzand, Bryan J Wells, Yazan Duwayri, Olamide Alabi, Ravi R Rajani, Luke P Brewster, Edmund K Waller, Arshed A Quyyumi
Abstract
Background: Lower extremity peripheral arterial disease (PAD) is a public health problem and many patients with PAD experience claudication despite adequate medical and/or surgical management. Mobilization of endogenous progenitor cells using Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) is a novel therapeutic option that has shown promising results in experimental models and phase I/IIA clinical trials. The GPAD-3 trial will study the effect of two successive administrations of GM-CSF at 3-month interval for improving claudication among patients with lower extremity PAD.
Methods: We plan to recruit 176 patients in this ongoing randomized, double-blind, placebo-controlled Phase IIB trial. After screening for inclusion and exclusion criteria, eligible subjects undergo a 4-week screening phase where they perform subcutaneous placebo injections thrice weekly and walk at least three times a day until they develop claudication. After the screening phase, eligible subjects undergo baseline testing and are randomized 2:1 to receive 500 μg/day of GM-CSF subcutaneously thrice weekly for three weeks or placebo injections. After 3 months, follow-up endpoint testing is performed and subjects in the GM-CSF group receive the second administration of the drug for three weeks while subjects in placebo group receive matching placebo injections. All participants undergo endpoint testing at six-month and nine-month follow-up. The primary endpoint is change in 6-min walk distance between baseline and 6-month follow-up.
Conclusion: GPAD-3 explores a novel approach to address the need for alternative therapies that can alleviate symptoms among patients with lower extremity PAD. If successful, this study will pave the way for a pivotal Phase III trial.
Trial registration: ClinicalTrials.gov NCT03304821.
Keywords: Angiogenesis; Claudication; GM-CSF; Peripheral artery disease.
Conflict of interest statement
Declaration of Competing Interest No authors have any competing interests.
Copyright © 2020. Published by Elsevier Inc.
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Source: PubMed