What Is RGN-259?
RGN-259 is a drug currently under investigation, primarily as a preservative-free, sterile eye drop solution. It contains Thymosin beta 4 (Tβ4) as its active ingredient. Tβ4 is a naturally occurring protein involved in cell migration, differentiation, and survival, which may contribute to tissue repair and anti-inflammatory effects in the eye. RGN-259 is being studied for its potential to treat various ocular surface conditions.
Clinical trials for RGN-259 began in 2015, with the latest trial starting in 2022. A total of 5 trials have been conducted or are ongoing, involving 1,706 participants. These studies are sponsored by ReGenTree, LLC.
Uses and Conditions Under Study
RGN-259 is being investigated for its potential to treat several eye conditions, focusing on the ocular surface. These conditions primarily involve issues with tear film stability, corneal health, and inflammation.
- Dry Eye Conditions: This category includes Dry Eye Syndrome, Dry Eye, and Dry Eye Syndromes, which have been studied across 4 trials. These conditions are characterized by insufficient tear production or poor tear quality, leading to discomfort, irritation, and potential damage to the eye's surface. RGN-259, as an eye drop containing Tβ4, is thought to help by promoting healing and reducing inflammation on the ocular surface, potentially improving symptoms and corneal health in patients with dry eyes.
- Neurotrophic Keratopathy: This severe degenerative disease of the cornea is being studied in 2 trials. Neurotrophic keratopathy results from damage to the nerves that supply the cornea, leading to a loss of sensation and impaired healing. This can cause persistent corneal defects, ulcers, and even vision loss. RGN-259's active ingredient, Tβ4, is believed to support corneal healing and regeneration, offering a potential treatment for this challenging condition.
Dosing
RGN-259 is administered as a preservative-free, sterile ophthalmic solution. The specific dosage form studied is 0.1% RGN-259 Opthalmic Solution, with trials also investigating "High Dose RGN-259" and "Low Dose RGN-259" to determine optimal concentrations.
Based on the clinical trials, RGN-259 has been studied with varying dosing regimens:
- Some studies involved direct instillation into the affected eye(s) five times per day for a duration of 28 days or 4 weeks.
- Other trials investigated instillation into each eye four times a day (QID) for either 14 days or 28 days.
These different regimens reflect the ongoing research to establish the most effective and safe way to use RGN-259 for the conditions under study.
Side Effects
In a clinical trial involving 299 patients treated with RGN-259, the most commonly reported side effect was nasopharyngitis (common cold symptoms), occurring in 3.0% of patients taking RGN-259 compared to 2.0% of patients on placebo. Other side effects reported in this trial included:
- Upper respiratory tract infection: 1.0% of patients on RGN-259 compared to 0.3% on placebo.
- Eye pain: 1.0% of patients on RGN-259 compared to 0.3% on placebo.
- Sinusitis: 1.0% of patients on RGN-259 compared to 1.0% on placebo.
In a separate, smaller study involving 10 patients, some eye-related side effects were observed more frequently with RGN-259 than with placebo. These included:
- Corneal epithelium defect: 20.0% of patients on RGN-259 experienced this, compared to 0.0% on placebo.
- Blood glucose decreased: 10.0% of patients on RGN-259 compared to 0.0% on placebo.
- Vitreous detachment: 10.0% of patients on RGN-259 compared to 0.0% on placebo.
- Corneal opacity: 10.0% of patients on RGN-259 compared to 0.0% on placebo.
- Inflammation: 10.0% of patients on RGN-259 compared to 0.0% on placebo.
- Keratic precipitates: 10.0% of patients on RGN-259 compared to 0.0% on placebo.
It is important to note that visual acuity reduced was less common in patients taking RGN-259 (0.3%) compared to placebo (3.3%) in the larger trial. Similarly, visual impairment was less common in patients taking RGN-259 (10.0%) compared to placebo (12.5%) in the smaller study.
Clinical Trial Results
Neurotrophic Keratopathy (NCT02600429)
In the SEER-1 study, RGN-259 was evaluated for the treatment of neurotrophic keratopathy. Key findings included:
- Corneal Sensitivity: Patients treated with RGN-259 showed improved corneal sensitivity, with mean measurements of 12.87 mm and 11.77 mm, compared to 18.33 mm and 14.38 mm for patients on placebo. Lower measurements indicate better sensitivity.
- Complete Healing: At Day 29, 6 out of 10 participants treated with RGN-259 achieved complete healing, compared to 1 out of 10 participants on placebo.
- Ocular Discomfort: Patients receiving RGN-259 reported lower (better) ocular discomfort scores, ranging from -1.4 to -2.0 on a scale, while placebo patients reported scores ranging from -0.1 to -0.6.
- Tear Film Break-up Time: RGN-259 treatment resulted in longer tear film break-up times, with mean values up to 6.217 seconds, compared to a maximum of 4.018 seconds for placebo. Longer times indicate improved tear film stability.
Other outcomes from this study included epithelial defect measurements, intraocular pressure, and visual acuity. For intraocular pressure, RGN-259 showed mean values of 18.0 mmHg and 16.8 mmHg, while placebo showed 12.5 mmHg and 14.5 mmHg. Visual acuity (logMAR) for RGN-259 ranged from 1.280 to 1.451, compared to 0.990 to 1.090 for placebo, where lower logMAR values indicate better vision.
Dry Eye Syndrome (NCT02974907)
The ARISE-2 study investigated RGN-259 for dry eye syndrome. For corneal fluorescein staining, which measures damage to the corneal surface (lower scores are better), the mean score for patients on RGN-259 was 0.07, compared to -0.01 for placebo. For ocular discomfort (lower scores are better), the mean score for patients on RGN-259 was 0.07, compared to -0.04 for placebo. In both these measures, RGN-259 showed slightly higher scores than placebo.
Currently Recruiting Trials
RGN-259 is currently being investigated in clinical trials to evaluate its potential as a treatment for specific ophthalmic conditions. These studies aim to gather more information about the drug's safety and effectiveness in patients who may benefit from new therapeutic options.
One active study, "Assessment of the Safety and Efficacy of 0.1% RGN-259 Ophthalmic Solution for the Treatment of NK: SEER-2," is a pivotal Phase 3 trial sponsored by ReGenTree, LLC. This study, identified as NCT05555589, is designed to compare the effects of the 0.1% RGN-259 Ophthalmic Solution against a placebo for the treatment of Neurotrophic Keratopathy (NK). Neurotrophic Keratopathy is a rare degenerative disease of the cornea that can lead to significant vision impairment, and this trial seeks to understand if RGN-259 can offer a meaningful improvement for patients.
Researchers are seeking to enroll approximately 70 participants for this important study. As a Phase 3 trial, it represents a crucial step in the drug development process, aiming to confirm the findings from earlier studies on a larger patient population. The primary objective is to assess both the safety profile and the efficacy of RGN-259 in treating NK.
To be eligible for the SEER-2 trial, participants must be between the ages of 18 and 18 years. The study is open to individuals of all genders, but it is not designed for healthy volunteers or children. This focused approach ensures that the research specifically addresses the needs of patients living with Neurotrophic Keratopathy who meet the specific criteria for the study.
Where to Participate
The clinical trial for RGN-259, NCT05555589, is actively recruiting participants across a wide geographic area. There are 29 study sites located in 28 cities across 18 states, making participation accessible to many individuals. This broad reach helps ensure a diverse group of participants can contribute to the research.
Some of the top recruiting locations include:
- Cleveland, Ohio (2 sites)
- Loma Linda, California (1 site)
- Colorado Springs, Colorado (1 site)
- Longmont, Colorado (1 site)
- Danbury, Connecticut (1 site)
- Crystal River, Florida (1 site)
- Miami, Florida (1 site)
- Tampa, Florida (1 site)
- Sandy Springs, Georgia (1 site)
- Chicago, Illinois (1 site)
Potential participants for this trial must be between the ages of 18 and 18 years and can be of any gender. It is important to note that this study is specifically for patients with Neurotrophic Keratopathy and is not recruiting healthy volunteers or children.
Development Timeline
The journey of RGN-259 began with its first clinical trial initiated on November 5, 2015. Since then, ReGenTree, LLC has been the sole sponsor, consistently driving the development of this investigational drug. The company has overseen a total of 5 clinical trials, involving a significant number of participants, totaling 1,706 individuals.
Initially, the research for RGN-259 explored potential applications for conditions such as Irritable Bowel Syndrome with Constipation (IBS-C) and hyperphosphatemia. However, the development pipeline expanded to focus on ophthalmic conditions, specifically Dry Eye and Dry Eye Syndromes, demonstrating an evolving understanding of the drug's potential therapeutic areas.
The development has progressed through advanced stages, with four of the five trials reaching Phase 3, and one trial conducted as a Phase 2/Phase 3 study. This indicates a strong commitment to rigorous testing and evaluation in larger patient populations. The latest trial for RGN-259 commenced on September 27, 2022, marking a continued effort to bring this potential treatment forward.