Evaluation of the Clinical Safety of a Novel Peptide-Based Topical Therapeutic to Promote Corneal Regeneration
Abstract
Ocular trauma is one of the most common injuries reported by our Armed Forces, accounting for 16% of all injuries in the Middle Eastern wars. Traumatic eye injuries render these injured Service members significantly less likely to return to military duty and carry higher rates of lifelong disability relative to other traumatic injuries. The cornea is a thin layer that protects the front of the eye and is almost universally damaged by blast, burn, and chemical traumatic eye injuries. An intact cornea is essential for normal vision, while also acting as a vital barrier that prevents contaminants and bacteria from causing further harm to the eye. Corneal injuries are extremely painful and increase susceptibility to eye infection, and improper corneal healing or scarring can lead to lifelong impairment or loss of vision. As such, it is paramount to accelerate corneal healing while limiting excessive inflammation that exacerbates tissue damage and can cause corneal scarring. Unfortunately, the current standard of care treatments for corneal injuries, such as antibiotics and corticosteroids, do not accelerate or improve corneal wound healing, and surgical procedures are often required to restore eyesight. There is an urgent military need for new traumatic eye treatments that can improve corneal healing while also preventing damaging inflammation and that can be easily administered in the field and during definitive medical care. FirstString Research is focused on the development and advancement of new therapeutic products for inflammation and injury-based conditions. FirstString has developed a short peptide, aCT1, that modulates cellular junctions to decrease damaging inflammatory responses, prevent the spread of injury, and reboot the healing process to encourage healthy tissue regeneration. FirstString has led investigations of the topical aCT1 formulation (Granexin gel) through Investigational New Drug (IND) approval into evaluation in six clinical trials for multiple skin wounds and scarring. Ongoing preclinical studies and clinical trials show the efficacy and safety of aCT1/Granexin gel in the treatment of skin wounds, we hypothesize that aCT1 s mechanism of action would translate to enhanced corneal healing and regeneration following traumatic ocular injury. Through previous DoD contracts, we completed a comprehensive set of preclinical studies in animal models of corneal injuries simulating military-relevant traumatic events (e.g., blunt, burn, thermal, and chemical trauma, corrective surgery) to test the safety and efficacy of a novel aCT1 eye drop formulation. aCT1 eye drops significantly accelerated healing while reducing harmful inflammation, with no signs of irritation or toxicity in animal models. The ophthalmic formulation containing aCT1 is stable with no significant degradation of peptide or pH changes when stored at appropriate temperatures in an innovative multidose delivery system, which enables easy administration in any setting. We propose to build on promising preclinical data and completed formulation milestones to execute the final steps required for FDA approval and clinical trial evaluation of the novel ophthalmic aCT1 formulation. Our proposal objectives are: (1) Completion of an IND-enabling GLP toxicity and ocular distribution study in a large animal model; (2) Compilation and submission of an Investigational New Drug (IND) application; (3) cGMP aCT1 eye drop scale-up and manufacturing for clinical investigation; and (4) Completion of a Phase 1 safety clinical study in normal, healthy volunteers. The proposed efforts are scheduled with milestones over a 2-year time period. Achieving these objectives will enable us to conduct a Phase II clinical trial to evaluate the efficacy of aCT1 in the treatment of corneal injuries, a vital step towards demonstrating the specific applicability and potential of aCT1 eye drops in the management of ocular trauma. The aCT1 eye drop represents a significant adv
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010879
Entities
People
- Gautam Ghatnekar
Organizations
- FirstString Research (United States)
- United States Army