R33EY036947

Translational studies to advance filociclovir to IND submission for the treatment of adenoviral conjunctivitis and acute keratoconjunctivitis - project summary/abstract.

The long-term goal of this project is to develop filociclovir (FCV) for the safe and effective treatment of human adenovirus (HADV) ocular infections, especially HADV-related epidemic keratoconjunctivitis (EKC), a stated National Eye Institute (NEI) research priority.

There are currently no treatments for patients suffering from adenoviral conjunctivitis, which is responsible for up to 8.5 million lost work days and $1.9 billion in lost wages every year in the U.S., or EKC, the most severe form of ocular adenoviral infection, which often causes long-term visual sequelae, such as chronic keratitis and vision loss.

As FCV has previously completed Phase 1 clinical studies for a systemic indication of cytomegalovirus (CMV) infection in solid organ transplant recipients, the objective of this R33 proposal is to generate the remaining ocular-specific preclinical (PC) data needed to support an Investigational New Drug (IND) submission to treat ocular HADV infections.

In this proposal, final formulation work and IND-enabling GLP-toxicity studies will be completed, along with confirmatory efficacy parameters, suitable for IND submission.

We will continue to communicate with the FDA to ensure that the correct study designs are in place.

The specific aims of this proposal, along with the research design and milestones, are as follows:

Aim 1. Finalize eye drop formulation with suitable preservatives, confirm efficacy in the rabbit HADV infection model and select a device (eye dropper) (Year 1).

Milestones: Formulation suitable for two species IND-enabling GLP toxicity and advancement into human studies, formulation passes antimicrobial effectiveness testing (AET), efficacy in rabbit eye model and final device selected.

Aim 2. Perform IND-enabling GLP ocular toxicity in rabbits and dose range-finding ocular tolerance and GLP ocular toxicity in rats (Years 2-3).

Milestones: Completion of acute tolerance studies in rats, GLP 14-day ocular toxicity in rabbits and rats to support an IND filing, NOAEL ≥ 0.5% dosed QID.

Aim 3. Complete regulatory requirements, including communications with the FDA, IND application and clinical trial design (Years 2-3).

Milestones: Pre-IND meeting with the FDA (follow-up to the Type C meeting held January 3, 2024), IND application and clinical trial design completed.

Microbiotix

1) TO SUPPORT EYE AND VISION RESEARCH PROJECTS THAT ADDRESS THE LEADING CAUSES OF BLINDNESS AND IMPAIRED VISION IN THE U.S. THESE INCLUDE RETINAL DISEASES, CORNEAL DISEASES, CATARACT, GLAUCOMA AND OPTIC NEUROPATHIES, STRABISMUS, AMBLYOPIA, AND LOW VISION AND BLINDNESS REHABILITATION. 2) TO INCREASE UNDERSTANDING OF THE NORMAL DEVELOPMENT AND FUNCTION OF THE VISUAL SYSTEM IN ORDER TO BETTER PREVENT, DIAGNOSE, AND TREAT SIGHT-THREATENING CONDITIONS, AND, TO ENHANCE THE REHABILITATION, TRAINING, AND QUALITY OF LIFE OF INDIVIDUALS WHO ARE PARTIALLY-SIGHTED OR BLIND. 3) TO SUPPORT A BROAD PROGRAM OF BASIC VISION RESEARCH THROUGH GRANTS AND COOPERATIVE AGREEMENTS, TO ENCOURAGE HIGH QUALITY CLINICAL RESEARCH, INCLUDING CLINICAL TRIALS, OTHER EPIDEMIOLOGICAL STUDIES, AND HEALTH SERVICES RESEARCH, TO ENCOURAGE RESEARCH TRAINING AND CAREER DEVELOPMENT IN THE SCIENCES RELATED TO VISION, AND TO SPONSOR SCIENTIFIC WORKSHOPS IN HIGH PRIORITY RESEARCH AREAS TO ENCOURAGE EXCHANGE OF INFORMATION AMONG SCIENTISTS. 4) SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO ENCOURAGE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.867 - Vision Research

National Eye Institute (NEI) [HHS - NIH]

Worcester, Massachusetts 016054307 United States

Single Zip Code

NEI Translational Research Program for Therapeutics (R33 Clinical Trial Not Allowed) (PAR-23-205)

Amendment Since initial award the total obligations have increased 99% from $674,963 to $1,344,822.