Keratoconus
Conditions
Keywords
keratoconus, eyedrops, non-invasive, Transforming Growth Factor
Brief summary
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.
Detailed description
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.
Interventions
DRUGLow-dose TGF-B3 and Dexamethasone Sodium Phosphate
Low-dose TGF-B3 and Dexamethasone Sodium Phosphate
DRUGHigh-dose TGF-B3 and Dexamethasone Sodium Phosphate
High-dose TGF-B3 and Dexamethasone Sodium Phosphate
Sponsors
TheiaNova Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a two-arm study investigating a low and a high dose of TN-001. A total of 20 participants will be enrolled (ten in each arm).
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participant-reported ocular tolerability score (5-point scale) | Baseline (Day 1) to Day 180 of treatment initiation | Participant-reported ocular tolerability was assessed using a study-specific eye questionnaire measured on a 5-point ordinal scale in the treatment eye. |
| Incidence of ocular and peri-ocular inflammation by slit-lamp examination | Baseline (Day 1) through Day 180 | Incidence of inflammation of the eye and surrounding tissues, including redness, aqueous cells, flare, limbus, fornices, tear ducts, and meibomian glands, assessed by slit-lamp microscopy using the Efron scale or a similar numerical grading scale in the treatment eye. |
| Incidence of corneal scarring and conjunctival inflammation | Baseline (Day 1) through Day 180 | Incidence of corneal scarring and conjunctival inflammation assessed by slit-lamp microscopy using the Efron scale or a similar numerical grading scale in the treatment eye. |
| Increase from baseline in intraocular pressure (mmHg) | Baseline (Day 1) through Day 180 | Increase from baseline in intraocular pressure measured using a hand-held tonometer (mmHg) in the treatment eye. |
| Change from baseline in endothelial cell count (cells/mm²) | Baseline (Day 1) through Day 180 | Change from baseline in endothelial cell count measured using specular microscopy (cells/mm²) in the treatment eye. |
| Change from baseline in endothelial cell characteristics | Baseline (Day 1) through Day 180 | Change from baseline in endothelial cell characteristics, including coefficient of variation and percentage of hexagonal cells, measured using specular microscopy in the treatment eye. |
| Incidence of structural corneal and ocular surface changes | Baseline (Day 1) through Day 180 | Incidence of structural changes of the cornea and ocular surface, including corneal opacities, corneal haze, and keratitis, assessed by anterior segment optical coherence tomography in the treatment eye. |
| Change from baseline in stromal thickness (microns) | Baseline (Day 1) through Day 180 | Change from baseline in stromal thickness measured in microns using anterior segment optical coherence tomography in the treatment eye. |
| Change from baseline in choroidal and retinal thickness | Baseline (Day 1) through Day 180 | Change from baseline in choroidal and retinal thickness measured using optical coherence tomography in the treatment eye. |
| Incidence of abnormal findings on dilated fundus examination | Baseline (Day 1) through Day 180 | Incidence of pathology involving the retina, optic nerve, lens, and/or macula assessed by dilated fundus examination using slit-lamp microscopy with a fundus lens in the treatment eye. |
| Change from baseline in visual acuity (LogMAR) | Baseline (Day 1) through Day 180 | Change from baseline in visual acuity measured using a LogMAR chart in the treatment eye. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in corneal stiffness and biomechanics | Baseline (Day 1) to Day 180 of treatment initiation | Change from baseline in corneal stiffness and biomechanical parameters measured using the Oculus Corvis® ST in the treatment eye. |
| Change from baseline in maximum corneal curvature (Kmax) | Baseline (Day 1) through Day 180 | Change from baseline in maximum corneal curvature measured using central keratometry (Kmax) with the Oculus Pentacam in the treatment eye. |
| Change from baseline in mean central corneal curvature | Baseline (Day 1) through Day 180 | Change from baseline in mean central corneal curvature measured using keratometry with the Oculus Pentacam in the treatment eye. |
| Change from baseline in corneal thickness (pachymetry) | Baseline (Day 1) through Day 180 | Change from baseline in corneal thickness (pachymetry), measured in microns using the Oculus Pentacam in the treatment eye. |
| Change from baseline in corneal shape (Belin ABCD parameters) | Baseline (Day 1) through Day 180 | Change from baseline in corneal shape assessed using Belin ABCD parameters measured with the Oculus Pentacam in the treatment eye. |
| Change from baseline in corneal higher-order aberrations | Baseline (Day 1) through Day 180 | Change from baseline in corneal higher-order aberrations, including spherical and coma-like aberrations, measured using Pentacam wavefront aberrometry in the treatment eye. |
Countries
Australia
Outcome results
None listed