Study of TN-001 Topical Eyedrops for Keratoconus

A Proof of Concept, Open-label, Two-arm Study to Investigate the Safety and Preliminary Efficacy of TN-001 Topical Eyedrops in Male and Female Patients With Progressive Keratoconus.

The goal of this clinical trial is to learn if TN-001, a new eye-drop therapy, is safe and well-tolerated in adult patients with progressive keratoconus. It will also provide data on whether this therapy is effective in treating keratoconus.

The main questions it aims to answer are:

What medical problems do participants have when using TN-001 eyedrops? Does TN-001 eyedrop therapy stop keratoconus from progressing further?

Participants will:

Take TN-001 eyedrops twice a day, every day, for 3-6 weeks. Visit the clinic once every week for checkups and tests. Keep a diary of their symptoms.

TN-001, the study drug, is a topical eyedrop containing Transforming Growth Factor Beta 3 (TGFB3) and Dexamethasone Sodium Phosphate (DexSP). It is anticipated that TN-001 may produce collagen in the eye, which is believed to stiffen the cornea. Stiffening of the cornea is desirable in patients with keratoconus as it helps to stop disease progression.

The purpose of this study is to:

• Evaluate the safety of TN-001
• Evaluate whether TN-001 eye drops are well tolerated in and around the eye
• Provide an initial indication on whether TN-001 may be effective in treating progressive keratoconus.
• Provide an indication of the duration of treatment impact.

Inclusion Criteria:

1. Participants must be 18 to 40 years of age inclusive, at the time of signing the informed consent.
2. Diagnosed with progressive keratoconus in one or both eyes.
3. Minimum corneal thickness equal to or greater than 400 microns.
4. Maximum corneal keratometry of 45 D to 54 D.
5. Willing and able to comply with all clinic visits and study-related procedures and instructions.
6. Able to self-medicate or be assisted with applying study eye drops twice daily for trial duration.
7. Provide signed informed consent to participate in the study.

Exclusion Criteria:

1. Concurrent use of contact lenses, including rigid gas permeable lenses
2. Known allergy to steroids, growth factors or gellan gum
3. Presence of ocular surface inflammation at any screening visit
4. Recurrent corneal erosions
5. Significant central corneal scarring or hydrops
6. Previous corneal cross-linking
7. Previous corneal transplant
8. Previous corneal or intraocular surgeries
9. Presence of any other ocular disease of the eye (not limited to cornea) e.g. glaucoma, uveitis, uncontrolled diabetic retinopathy
10. Presence or history of ocular cancer
11. Prior ocular trauma or prior retinal detachment involving the macula
12. Received an ocular corticosteroid within the past 6 months (within the past 3 months, for topical ocular corticosteroids), or any intravitreal injection within the last 6 months in the study eye prior to day 0
13. Any severe comorbid condition or other issue that renders the participant unsuitable for participation in the study
14. A comorbid condition with an estimated life expectancy of ≤6 months at the time of consent
15. Systemic comorbidities that pose a significant surgical risk
16. Current use or anticipated use during the study of a systemic corticosteroid with a dose greater than 10mg daily, or an immunosuppressant agent by any route (oral, injectable)
17. Current use or anticipated use during the study of medicated lubricating eye drops or topical ophthalmic antihistamines
18. History of connective tissue disorders, collagenoses, collagen vascular diseases, autoimmune or other immune deficiency disease
19. Pregnancy or planning to become pregnant
20. Participation in another interventional clinical trial within 30 days or 5 half-lives of that Investigational Product prior to consent for this trial, or planning to participate in another clinical trial at the time of consent
21. Known alcohol, drug or medication abuse within 1 year prior to consent for this study
22. Treatment with an anticancer therapy (chemotherapy, immunotherapy, radiotherapy, targeted therapy or gene therapy) within 3 months prior to day 0 or at any time during the study. Recovery from any associated toxicities must be documented prior to inclusion
23. Mental condition rendering the participant unable to understand the nature, scope, and possible consequences of the study
24. Participants who are employees of the Sponsor, study site or their immediate families
25. Inability or unwillingness to comply with all follow-up through to the end of the study, and/or unwilling to allow access to review medical records in accordance with local regulatory requirements at the time of consent
26. Retinal disease, including proliferative diabetic retinopathy, retinal fibrosis, neovascular age-related macular degeneration
27. Participants in whom corneal thinning has stabilized by ophthalmologist's opinion during screening
28. Myopic degeneration with potential acuity less than 20/40 in either eye
29. Any reason for which in the opinion of the principal investigator the participant should not be enrolled into the study