SEER-3: A Phase 3, Multi-Center, Randomized, Parallel, Double Masked, Placebo-Controlled Clinical Study to Assess the Safety and Efficacy of 0.1% RGN-259 Ophthalmic Solution for the Treatment of Neurotrophic Keratopathy
- Trial ID
- 2022-502697-16-00
- Protocol
- SEER-3
- Sponsor
- Regentree LLC
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this clinical study is to evaluate the **safety** and **efficacy** of RGN-259, a 0.1% timbetasin acetate ophthalmic solution, compared 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 and potential vision loss. Assessing the therapeutic potential of RGN-259 is clinically relevant as it may offer a novel treatment option for patients suffering from this challenging condition. There are no secondary objectives outlined for this study.
Participants
The clinical trial focuses on evaluating the safety and efficacy of RGN-259 compared to placebo for the treatment of **Neurotrophic Keratopathy**. The study population includes both male and female participants of any race, aged 18 years and older. Participants are required to have a Persistent Epithelial Defect in one or both eyes, with stage 2 or 3 neurotrophic keratopathy as per the Mackie Classification. The trial does not involve a vulnerable population. Participants must have a decreased corneal sensitivity and a BCVA score of 75 letter counts or less in the study eye. Female participants of child-bearing potential must use contraception and have a negative pregnancy test. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity.
Plans and Procedures
The clinical trial is designed to evaluate the **safety** and **efficacy** of 0.1% RGN-259 ophthalmic solution for the treatment of **neurotrophic keratopathy**. This is a Phase 3, multi-center, randomized, parallel, double-masked, placebo-controlled study. The trial aims to compare the investigational product, Timbetasin acetate ophthalmic solution, with a placebo that has an identical composition except for the absence of the active substance. The trial is expected to run from April 2023 to March 2025, with participant involvement lasting up to 4 weeks.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, such as age, gender, and the presence of a persistent epithelial defect. The primary endpoint is the percentage of subjects achieving complete healing of the defect by Day 29, as determined by corneal fluorescein staining. Safety will be assessed through the frequency and severity of adverse events, changes in vital signs, intraocular pressure, and results from dilated fundoscopy and slit-lamp exams.
Following the screening visit, participants will attend multiple follow-up visits to monitor progress and collect data on secondary endpoints, including the time to complete healing and changes in lesion size. The end-of-study visit will conclude the trial, assessing the final outcomes and any long-term effects. Participants may be withdrawn from the study if they experience significant adverse events or fail to comply with study protocols. The trial's design ensures rigorous assessment of the investigational product's therapeutic potential while maintaining participant safety and data integrity.
Treatment
The clinical trial involves the use of **Timbetasin acetate** ophthalmic solution 0.1%, which is an investigational medication formulated as eye drops in a solution contained within a single-dose container. The active substance, **timbetasin acetate**, is a synthetically produced protein, specifically a copy of the naturally occurring 43-amino acid peptide known as Thymosin beta 4 (Tβ4). The solution is administered via conjunctival use, with a maximum daily dose of 0.5% and a total maximum dose of 14% over a treatment period of up to four weeks. The medication is not a pediatric formulation and is designated as an orphan drug. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen.
The study also includes a placebo, which is identical in composition to the investigational product except for the absence of **timbetasin acetate**. The placebo serves as a comparator treatment to evaluate the safety and efficacy of the investigational medication. The placebo is administered in the same manner as the experimental treatment, ensuring that the study remains double-masked and placebo-controlled. This design allows for a rigorous assessment of the investigational product's therapeutic potential in treating **Neurotrophic Keratopathy**.
Efficacy
Efficacy in the clinical trial 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, as measured by the Central Reading Center. Safety will also be evaluated by monitoring the frequency and severity of adverse events, changes in vital signs, intraocular pressure, and results from dilated fundoscopy and slit-lamp exams.
Secondary endpoints include the percentage of subjects achieving complete healing of the PED at various visits, both as measured by the Central Reading Center and the Investigator. Time to complete healing and percentage change from baseline of lesion size will also be assessed. Additional parameters include the stage of Neurotrophic Keratopathy (Mackie Classification), visual acuity determined by the Early Treatment of Diabetic Retinopathy Study (ETDRS), and corneal sensitivity using the Cochet-Bonnet aesthesiometer. Changes in ocular discomfort, photophobia, foreign body sensation, burning, and dryness will be evaluated using a Visual Analog Scale (VAS) at specific visits.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Be male or female of any race, at least 18 years of age at Visit 1
- 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 protocol
- Have at least one eye (the same eye) satisfy all criteria for 4, 5, 6, 7 above
- Female subjects of child-bearing potential must be non-lactating and using and agree to continue using an acceptable method of contraception 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
- Male subjects must agree to use an adequate method of contraception
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 at Visit 1 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 the 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 (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. tarsorraphy, 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® injection to induce blepharoptosis in the study eye within 90 days prior to Visit 1
- Have used contact lenses (for therapeutic 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 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 (eg, 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 anti-histamine drugs including oral pilocarpine and cevimeline, cholinergics including nasal varenicline, cytotoxic cancer therapy, neuroleptics, and antipsychotics) 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)
- q. 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
- History of drug, medication or alcohol abuse or addiction
- 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
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Not Recruiting | 01 Apr 2023 | 10 |
 Italy | Not Recruiting | 01 Apr 2023 | 20 |
 Poland | Not Recruiting | 01 Apr 2023 | 20 |
 Spain | Not Recruiting | 01 Apr 2023 | 20 |
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 |
|---|---|---|---|---|---|---|
Timbetasin acetate ophthalmic solution 0.1% | Test | EYE DROPS, SOLUTION IN SINGLE-DOSE CONTAINER | CONJUNCTIVAL USE | 0.5 | 4 | PRD10194926 |
The placebo has the identical composition as the DP except it does not contain timbetasin acetate. | Placebo | N/A | — | — | — | N/A |