Evaluation of Timbetasin Acetate Ophthalmic Solution 0.1% for Neurotrophic Keratopathy: A Phase 3 Randomized, Double-Masked, Placebo-Controlled Study
- Trial ID
- 2024-518969-98-00
- Protocol
- RGN-NK-302
- Sponsor
- Regentree LLC
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this Phase 3, multi-center, randomized, parallel, double-masked, placebo-controlled clinical study is to compare the **safety** and **efficacy** of RGN-259, a timbetasin acetate ophthalmic solution, to placebo in the treatment of **Neurotrophic Keratopathy**. This condition is a degenerative disease of the corneal epithelium caused by impaired corneal innervation, leading to corneal ulceration, scarring, and vision loss. Evaluating the safety and efficacy of RGN-259 is clinically relevant as it may offer a therapeutic option for patients suffering from this challenging condition, potentially improving corneal healing and preserving vision.
Participants
The clinical trial for the treatment of **Neurotrophic Keratopathy** involves a total of 35 participants. The study population includes both male and female subjects, aged 18 years and older, without any specific racial restrictions. Participants are required to be in general good health, with the ability to provide written informed consent and comply with study procedures. The selection criteria ensure that subjects have a Persistent Epithelial Defect in one or both eyes, which has not resolved after one week of conventional treatment. The trial does not include vulnerable populations. Lifestyle factors such as diet and physical activity are not specified as part of the selection criteria. The study population was selected based on specific ophthalmic conditions, including stage 2 or 3 neurotrophic keratopathy, and decreased corneal sensitivity, as confirmed by the investigator. Both male and female participants must adhere to specific contraceptive guidelines to ensure safety throughout the trial duration.
Plans and Procedures
The clinical trial is a **Phase 3**, multi-center, randomized, parallel, double-masked, placebo-controlled study designed to assess the safety and efficacy of 0.1% RGN-259 ophthalmic solution for the treatment of **Neurotrophic Keratopathy**. The trial aims to compare the investigational product, RGN-259, with a placebo, which is identical in composition except for the exclusion of the active ingredient, **timbetasin acetate**. The study is structured to ensure rigorous evaluation through a double-masked approach, where neither the participants nor the investigators are aware of the treatment assignments, thereby minimizing bias.
The trial is expected to commence recruitment on March 10, 2025, and conclude by November 25, 2025. Participants will be involved in the study for a maximum of 6 weeks, with the treatment period lasting up to 4 weeks. The study includes several key visits: an initial screening visit to confirm eligibility, followed by multiple follow-up visits to monitor progress and assess outcomes. The primary endpoint is the percentage of subjects achieving complete healing of the Persistent Epithelial Defect (PED) at Day 29, as determined by corneal fluorescein staining. Secondary endpoints include various measures of healing and symptom changes assessed at multiple visits throughout the study.
Participants will be required to attend a series of visits, starting with the inclusion (screening) visit, where eligibility criteria such as age, presence of a Persistent Epithelial Defect, and stage of Neurotrophic Keratopathy will be confirmed. Follow-up visits will occur at regular intervals to evaluate the primary and secondary endpoints, including corneal healing and symptom relief. The end-of-study visit will finalize data collection and ensure participant safety post-treatment.
Involvement in the study may be terminated early if participants experience adverse events, fail to comply with study procedures, or withdraw consent. The trial is designed to ensure participant safety and data integrity, with strict adherence to the protocol and regulatory requirements. The study's findings will contribute to understanding the therapeutic potential of RGN-259 in treating Neurotrophic Keratopathy.
Treatment
The clinical trial involves the administration of **Timbetasin acetate ophthalmic solution 0.1%**, a synthetic peptide formulated as eye drops in a solution contained within single-dose containers. The active substance, timbetasin acetate, is classified as a protein of other origin. The pharmaceutical form is specifically designed for **conjunctival use**, ensuring targeted delivery to the ocular surface. The dosing regimen involves a maximum daily dose of 1 mg, with a total maximum dose of 28 mg over a treatment period of 4 weeks. The administration schedule is structured to maintain consistent therapeutic levels, and participant compliance is monitored through regular assessments.
The study also includes a **placebo** group, which receives a formulation identical to the test product, excluding the active ingredient, timbetasin acetate. The placebo is manufactured using the same process and packaged in the same container closure system as the experimental medication, ensuring blinding integrity. The placebo is administered via the **ophthalmic route**, mirroring the administration method of the active treatment. The placebo group follows a similar dosing schedule, with a maximum treatment period of 6 weeks, to facilitate a robust comparison of safety and efficacy outcomes between the active and placebo groups.
Efficacy
The efficacy of the investigational product, RGN-259 ophthalmic solution, in the treatment of **Neurotrophic Keratopathy** will be assessed through a series of primary and secondary endpoints. The primary endpoint is the percentage of subjects achieving complete healing of the Persistent Epithelial Defect (PED), defined as a 0 mm lesion size, at Visit 5 (Day 29). This will be determined by corneal fluorescein staining, with measurements conducted by the Central Reading Center.
Secondary endpoints include the percentage of subjects achieving complete healing of the PED, defined as less than 0.5 mm lesion size, as measured by the Investigator at Visit 5. Additional assessments will be conducted at Visits 2, 3, 4, 6, and 7, evaluating both complete healing and percentage change from baseline in lesion size. These measurements will be performed using corneal fluorescein staining by both the Central Reading Center and the Investigator. Other secondary endpoints involve the assessment of **Visual Acuity** using the Early Treatment of Diabetic Retinopathy Study (ETDRS) chart, corneal sensitivity using the Cochet-Bonnet aesthesiometer, and changes in ocular discomfort and other symptoms using the Visual Analog Scale (VAS) and the SANDE questionnaire at specified visits.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Be male or female of any race, at least 18 years of age
- Have provided written informed consent
- Be able and willing to follow instructions, including participation in all study assessments and visits
- At the time of Visit 1, have documentation or observation of a Persistent Epithelial Defect (PED) in one or both eyes, defined as a corneal epithelial defect that has not resolved after 1 week of conventional treatment using non-preserved ocular lubricants, non-preserved topical ophthalmic antibiotics, oral doxycycline, patching, amniotic membrane, serum tears, and/or therapeutic contact lenses; Note that re-screened subjects who failed conventional treatment needs to go through 1 week of conventional treatment again right before Visit 1
- Have stage 2 or 3 neurotrophic keratopathy (Mackie Classification) in at least one eye of which the longest dimension (length or width) of the defect measures a minimum length of 1 mm (study eye) and which is confirmed by the Investigator not to be simply superficial punctate keratitis, at Visit 1
- Have evidence of decreased corneal sensitivity ≤40 mm (average of 3 measurements) within the area of the PED or corneal ulceration and outside of the area of the defect within 3 mm of the central cornea using the Cochet-Bonnet aesthesiometer at Visit 1
- Have BCVA score ≤75 letter counts in the study eye based on the ETDRS chart
- Have at least one eye (the same eye) satisfy all criteria for d, e, f, g above
- Female subjects not pregnant or breastfeeding fulfilling one of the following criteria: 1. woman of childbearing potential (WOCBP) using and agree to continue using a contraceptive method that is highly effective (with a failure rate of <1% per year and, preferably, with low user dependency) for at least 4 weeks prior to the first dose of study product and until 12 weeks after last dose, and have a negative urine pregnancy test during screening; OR 2. woman of nonchildbearing potential defined as physiologically incapable of becoming pregnant (i.e., permanently sterile or post-menopausal)
- Male subjects fulfilling one of the following criteria: 1.Male subjects with pregnant or non-pregnant women of childbearing potential (WOCBP) partners: they must be willing to use a male condom from the time of signing of the informed consent and until 12 weeks after last dose of the study product (and should be advised of the benefit for a female partner to use highly effective method of contraception, as a condom may break or leak); OR 2. Male subjects with partners not of childbearing potential (contraception is not required in this case); OR 3. Non-fertile male subjects (contraception is not required in this case).
Exclusion Criteria
- Have any condition that, in the opinion of the Investigator, would interfere with the subject’s ability to complete the study, would interfere with the interpretation of safety or efficacy, or would present an undue risk to the subject. In cases of uncertainty, the Investigator should contact the medical monitor for clarification
- Have any clinically significant slit-lamp findings in the study eye that in the opinion of the Investigator may interfere with the study parameters; Examples include stromal keratitis, numerous punctate keratitis or pterygium, and thin cornea
- Clinically significant active blepharitis, meibomian gland dysfunction (MGD), or lid margin inflammation, or active ocular allergy in study eye that requires treatment that in the opinion of the Investigator may interfere with study parameters
- Have a Unanesthetized Schirmer’s test score of ≤3 mm at Visit 1
- Have a lid function abnormality (ex. Lagophthalmos) which, in the opinion of the Investigator, is the primary cause of the persistent epithelial defect
- Have an ongoing ocular infection (bacterial, viral or fungal) or active inflammation (e.g., follicular conjunctivitis) in the study eye. Note that subjects with active stromal herpetic keratitis will also be excluded
- History of any ocular surgery in the study eye (including laser or refractive surgical procedures) within the three months before study enrollment. Ocular procedures that are the cause of NK that occurred within 3 months prior to Visit 1 are not exclusionary
- Prior surgical procedure(s) for the treatment of NK (e.g., tarsorrhaphy, conjunctival flap, etc.) within the three months before study enrollment with the exception of amniotic membrane transplantation. Subjects previously treated with amniotic membrane transplantation may only be enrolled after the membrane has disappeared within the area of the PED or at least four weeks after the date of the amniotic membrane transplantation procedure
- Have any planned ocular surgical procedures or are likely to require ocular surgery for the study eye during the study
- Have received Botox® (OnabotulinumtoxinA) injection to induce blepharoptosis in the study eye within 90 days prior to Visit 1
- Have used contact lenses (for therapeutic (including bandage contact lenses) or refractive correction) in the study eye within 14 days prior to Visit 1, or anticipate use of contact lenses during the study period. Note that consented subjects will be instructed to discontinue use of contact lenses for the study eye throughout the study
- Have used OxervateTM (cenegermin-bkbj) in the study eye within the past 2 months
- Anticipate use of serum tears in the study eye during the study period. Note that use of preservative free artificial tears for at least two weeks at the time of screening may continue throughout the study at the discretion of the Investigator
- Have a presence or history of any ocular or systemic disorder or condition that might hinder the efficacy of the study treatment or its evaluation, could possibly interfere with the interpretation of study results, or could be judged by the Investigator to be incompatible with the study visit schedule or conduct (e.g., progressive or degenerative corneal or retinal conditions, optic neuritis, systemic infection, neoplastic diseases, poorly controlled diabetes)
- Have used drugs which affect lacrimation or function of the trigeminal nerve (e.g., neuroleptics, antipsychotics and antihistamine drugs including oral pilocarpine and cevimeline, cholinergics including nasal varenicline, cytotoxic cancer therapy) within 30 days of Visit 1 or anticipate use of these systemic medication throughout the course of the study
- Have any autoimmune or chronic inflammatory disease that might have hindered the efficacy of the study treatment or its evaluation, could possibly have interfered with the interpretation of study results, or could have been judged by the Investigator to be incompatible with the study visit schedule or conduct (e.g., psoriasis, systemic lupus erythematosus, giant cell arteritis, polyarteritis nodosa, relapsing polychondritis, scleroderma, Behcet’s disease, reactive arthritis, inflammatory bowel disease, ankylosing spondylitis, Graves' disease)
- Be on topical (ocular/nasal) immunosuppressive therapy within 30 days prior to screening or is likely to require this during the course of the study; Note that only Systemic and dermal immunosuppressive therapy (including inhalation) with a stable dose for at least two weeks at the time of Visit 1 is permitted
- Have a known allergy and/or sensitivity to the study product or its components, and history of allergy/hypersensitivity to fluorescein or to any of the excipients
- Have a history of drug, medication or alcohol abuse or addiction in past 2 years
- Have participated in an investigational drug study within 30 days prior to screening. In addition, it is necessary that at least 5 half-lives of the previously administered investigational drug have elapsed by Visit 1. Observational studies are not exclusionary
- Have fever, inflammation, or systemic signs of illness suggestive of systemic or invasive infection, including COVID-19 or a positive test for COVID-19, within 2 weeks prior to first dose of study drug
- Have been previously randomized in RGN-259 (SEER-3) clinical study
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Italy | Not Recruiting | 10 Mar 2025 | 10 |
 Poland | Not Recruiting | 10 Mar 2025 | 15 |
 Spain | Not Recruiting | 10 Mar 2025 | 10 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
The placebo matches the test product with identical composition (with the exclusion of the active ingredient, timbetasin acetate), manufactured using the same process and package in the same container closure system. | Placebo | N/A | OPHTHALMIC | — | 6 | N/A |
Timbetasin acetate ophthalmic solution 0.1% | Test | EYE DROPS, SOLUTION IN SINGLE-DOSE CONTAINER | CONJUNCTIVAL USE | 1 | 4 | PRD10194926 |