Study of TN-001 Topical Eyedrops for Keratoconus

Official title

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.

Overview

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

• Drug Low-dose TGF-B3 and Dexamethasone Sodium Phosphate
  Low-dose TGF-B3 and Dexamethasone Sodium Phosphate
• Drug High-dose TGF-B3 and Dexamethasone Sodium Phosphate
  High-dose TGF-B3 and Dexamethasone Sodium Phosphate

Primary outcome measures

• Participant-reported ocular tolerability score (5-point scale) [Time frame: Baseline (Day 1) to Day 180 of treatment initiation]
• Incidence of ocular and peri-ocular inflammation by slit-lamp examination [Time frame: Baseline (Day 1) through Day 180]
• Incidence of corneal scarring and conjunctival inflammation [Time frame: Baseline (Day 1) through Day 180]
• Increase from baseline in intraocular pressure (mmHg) [Time frame: Baseline (Day 1) through Day 180]
• Change from baseline in endothelial cell count (cells/mm²) [Time frame: Baseline (Day 1) through Day 180]
• Change from baseline in endothelial cell characteristics [Time frame: Baseline (Day 1) through Day 180]
• Incidence of structural corneal and ocular surface changes [Time frame: Baseline (Day 1) through Day 180]
• Change from baseline in stromal thickness (microns) [Time frame: Baseline (Day 1) through Day 180]
• Change from baseline in choroidal and retinal thickness [Time frame: Baseline (Day 1) through Day 180]
• Incidence of abnormal findings on dilated fundus examination [Time frame: Baseline (Day 1) through Day 180]

Secondary outcome measures (6)

• Change from baseline in corneal stiffness and biomechanics [Time frame: Baseline (Day 1) to Day 180 of treatment initiation]
• Change from baseline in maximum corneal curvature (Kmax) [Time frame: Baseline (Day 1) through Day 180]
• Change from baseline in mean central corneal curvature [Time frame: Baseline (Day 1) through Day 180]
• Change from baseline in corneal thickness (pachymetry) [Time frame: Baseline (Day 1) through Day 180]
• Change from baseline in corneal shape (Belin ABCD parameters) [Time frame: Baseline (Day 1) through Day 180]
• Change from baseline in corneal higher-order aberrations [Time frame: Baseline (Day 1) through Day 180]

Eligibility criteria

Inclusion criteria

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

Exclusion criteria

• Concurrent use of contact lenses, including rigid gas permeable lenses
• Known allergy to steroids, growth factors or gellan gum
• Presence of ocular surface inflammation at any screening visit
• Recurrent corneal erosions
• Significant central corneal scarring or hydrops
• Previous corneal cross-linking
• Previous corneal transplant
• Previous corneal or intraocular surgeries
• Presence of any other ocular disease of the eye (not limited to cornea) e.g. glaucoma, uveitis, uncontrolled diabetic retinopathy
• Presence or history of ocular cancer
• Prior ocular trauma or prior retinal detachment involving the macula
• 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
• Any severe comorbid condition or other issue that renders the participant unsuitable for participation in the study
• A comorbid condition with an estimated life expectancy of ≤6 months at the time of consent
• Systemic comorbidities that pose a significant surgical risk
• 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)
• Current use or anticipated use during the study of medicated lubricating eye drops or topical ophthalmic antihistamines
• History of connective tissue disorders, collagenoses, collagen vascular diseases, autoimmune or other immune deficiency disease
• Pregnancy or planning to become pregnant
• 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
• Known alcohol, drug or medication abuse within 1 year prior to consent for this study
• 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
• Mental condition rendering the participant unable to understand the nature, scope, and possible consequences of the study
• Participants who are employees of the Sponsor, study site or their immediate families
• 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
• Retinal disease, including proliferative diabetic retinopathy, retinal fibrosis, neovascular age-related macular degeneration
• Participants in whom corneal thinning has stabilized by ophthalmologist's opinion during screening
• Myopic degeneration with potential acuity less than 20/40 in either eye
• Any reason for which in the opinion of the principal investigator the participant should not be enrolled into the study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Australia · 1 center

• Ophthalmic Trials Australia — Brisbane

Publications

• Diekman BO, Rowland CR, Lennon DP, Caplan AI, Guilak F. Chondrogenesis of adult stem cells from adipose tissue and bone marrow: induction by growth factors and cartilage-derived matrix. Tissue Eng Part A. 2010 Feb;16(2):523-33. doi: 10.1089/ten.TEA.2009.0398. PMID 19715387
• CULLEN JF, BUTLER HG. MONGOLISM (DOWN'S SYNDROME) AND KERATOCONUS. Br J Ophthalmol. 1963 Jun;47(6):321-30. doi: 10.1136/bjo.47.6.321. No abstract available. PMID 14189698
• Carrington LM, Albon J, Anderson I, Kamma C, Boulton M. Differential regulation of key stages in early corneal wound healing by TGF-beta isoforms and their inhibitors. Invest Ophthalmol Vis Sci. 2006 May;47(5):1886-94. doi: 10.1167/iovs.05-0635. PMID 16638995
• Bawazeer AM, Hodge WG, Lorimer B. Atopy and keratoconus: a multivariate analysis. Br J Ophthalmol. 2000 Aug;84(8):834-6. doi: 10.1136/bjo.84.8.834. PMID 10906086
• Ambekar R, Toussaint KC Jr, Wagoner Johnson A. The effect of keratoconus on the structural, mechanical, and optical properties of the cornea. J Mech Behav Biomed Mater. 2011 Apr;4(3):223-36. doi: 10.1016/j.jmbbm.2010.09.014. Epub 2010 Oct 7. PMID 21316609

Identifiers

NCT: NCT07388069 · TN-001-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗