Dataset Information

A Phase 2 Trial to Test Safety and Efficacy of ST-100, a Unique Collagen Mimetic Peptide Ophthalmic Solution for Dry Eye Disease.

ABSTRACT:

Objective

Dry eye disease (DED) is a worldwide source of ocular discomfort. This first-in-human phase 2 clinical study determined the efficacy of treating signs and symptoms of DED using an ophthalmic solution of synthesized mimetic of human collagen (ST-100).

Design

This double-masked, randomized, study compared high (60 μg/mL) and low (22 μg/mL) dose ST-100 to vehicle utilizing the Ora, Inc. Controlled Adverse Environment (CAE) during a 28-day period.

Participants

Participants included males and females ≥ 18 years of age with signs and symptoms of DED for ≥ 6 months that worsened during CAE exposure who were not taking any topical prescription therapeutic.

Intervention

Participants applied ST-100 or vehicle placebo topically to both corneas (1 drop) twice daily via a blow-fill-sealed preservative-free container.

Main outcome measures

The prespecified primary efficacy sign end point was mean change from baseline (CFB) in total corneal fluorescein staining, and the primary symptom end point was mean CFB in ocular discomfort. A secondary prespecified efficacy end point was CFB in unanesthetized Schirmer's test for tear film production.

Results

Of 160 subjects in the intent-to-treat population (112 female, 48 male, median age 64), 146 completed the study. Total corneal fluorescein staining CFB improved for high-dose ST-100, with superiority over vehicle when both eyes were considered together (2-sample t test: P = 0.0394). High-dose ST-100 was superior to vehicle in Schirmer's CFB for the study eye (least squares mean difference [confidence interval] = 2.3 [0.6, 4.0], P = 0.0094). For study eyes, the proportion of Schirmer's test responders (CFB ≥ 10 mm, Schirmer's responder rate) was 12.2% for high-dose ST-100 versus 0.0% for vehicle (P = 0.0266). The CFB for ocular discomfort score improved in study eyes for high- and low-dose ST-100 (paired t test, P = 0.0133, P = 0.0151, respectively) but without superiority over vehicle (ANCOVA: P = 0.5696, P = 0.8968, respectively). ST-100 Schirmer's responders also demonstrated total elimination of worsening of corneal fluorescein stain during the stress of CAE sessions.

Conclusions

ST-100 significantly improved tear production and related outcomes in DED and was well-tolerated in reducing symptoms.

Financial disclosures

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

SUBMITTER: Baratta RO

PROVIDER: S-EPMC10838901 | biostudies-literature | 2024 May-Jun

REPOSITORIES: biostudies-literature

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Publications

A Phase 2 Trial to Test Safety and Efficacy of ST-100, a Unique Collagen Mimetic Peptide Ophthalmic Solution for Dry Eye Disease.

Baratta Robert O RO Schlumpf Eric E Del Buono Brian J BJ DeLorey Shawn S Ousler George G Calkins David J DJ

Ophthalmology science 20231212 3

<h4>Objective</h4>Dry eye disease (DED) is a worldwide source of ocular discomfort. This first-in-human phase 2 clinical study determined the efficacy of treating signs and symptoms of DED using an ophthalmic solution of synthesized mimetic of human collagen (ST-100).<h4>Design</h4>This double-masked, randomized, study compared high (60 μg/mL) and low (22 μg/mL) dose ST-100 to vehicle utilizing the Ora, Inc. Controlled Adverse Environment (CAE) during a 28-day period.<h4>Participants</h4>Partici ...[more]

PMID: 38317866

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Project description:BackgroundDry eye disease (DED) is a disorder characterized by loss of tear film homeostasis that causes ocular surface inflammation and damage. The incidence of DED increases with age. Cyclosporine ophthalmic solution 0.09% (CEQUA®; OTX-101), cyclosporine ophthalmic emulsion 0.05% (Restasis®; CsA), and lifitegrast ophthalmic solution 5% (Xiidra®; LFT) are anti-inflammatory agents indicated for DED. This analysis compared treatment patterns in patients with DED receiving OTX-101, CsA, or LFT.MethodsThis real-world, retrospective, longitudinal cohort study utilized Symphony Health Integrated Dataverse claims from July 2019 to June 2021. The dataset included all patients with OTX-101 claims and patients with CsA or LFT claims randomly selected 2:1 to OTX-101. Patients were sorted into 3 cohorts based on index treatment. Index date was that of first treatment claim, and follow-up period was from index date to end of clinical activity or data availability. Time to treatment discontinuation (TTD), probability of discontinuation, and treatment persistence were assessed for OTX-101 vs. CsA, then OTX-101 vs. LFT. Subgroup analysis was performed based on age and prior DED treatment. Kaplan-Meier analysis and log-rank test were used to examine TTD. A logistic model evaluated association between index treatment and discontinuation. Unadjusted and adjusted odds ratios, 95% confidence intervals, and P-values were reported, with statistically significant associations based on P-values < 0.05.ResultsOverall, 7102 patients (OTX-101 n = 1846; CsA n = 2248; LFT n = 3008) were eligible. Median TTD was 354 days for patients receiving OTX-101 vs. 241 days for CsA and 269 days for LFT. Log-rank test indicated TTD was significantly longer for patients on OTX-101 vs. CsA (P = 0.033). Patients on CsA were 35% more likely to discontinue treatment than patients on OTX-101; OTX-101 and LFT groups had similar discontinuation rates. After 360 days, 49.8% of patients receiving OTX-101 remained on treatment vs. 39.4% of patients on CsA (P = 0.036) and 44.0% of patients on LFT (P = 0.854).ConclusionsPatients receiving OTX-101 remained on treatment significantly longer and were significantly less likely to discontinue treatment than patients on CsA. Older patients remained on OTX-101 significantly longer than CsA. These findings highlight treatment pattern differences in patients with DED receiving these anti-inflammatory agents.

Project description:ImportanceDry eye disease (DED) is a prevalent eye disorder. Cyclosporine is an effective immunomodulator that is widely used in DED; however, due to its highly hydrophobic nature, delivery of cyclosporine to the ocular surface is challenging.ObjectiveTo evaluate the efficacy and safety of SHR8028, a water-free cyclosporine ophthalmic solution, 0.1%, compared with vehicle in Chinese participants with DED.Design, setting, and participantsThis was a multicenter, double-blind, vehicle-controlled, phase 3 randomized clinical trial conducted from March 4, 2021, to July 22, 2022. Adult participants with moderate to severe DED were recruited from 12 hospitals in China. Study data were analyzed April 2, 2022, for the primary analysis.InterventionsFollowing a 14-day run-in period with an artificial tear, participants were randomly assigned (1:1) to receive water-free cyclosporine or vehicle (1 eye drop in each eye twice daily). After a 29-day treatment, participants of both groups were given the option to receive water-free cyclosporine for an additional 12 weeks for longer-term safety assessment.Main outcomes and measuresThe primary end points were changes from baseline in total corneal fluorescein staining (tCFS) using the National Eye Institute scale and in dryness score on a visual analog scale at day 29.ResultsA total of 206 participants (mean [SD] age, 47.8 [14.2] years; 185 female [90%]) were enrolled, with 103 each in the cyclosporine group and the vehicle group. At day 29, the cyclosporine group experienced improved tCFS compared with vehicle (change [Δ] = -1.8; 95% CI, -2.7 to -1.0; P < .001), with a tCFS score decrease from baseline of -4.8 in the cyclosporine group and -3.0 in the vehicle group. Dryness score decreased from baseline in both groups (-19.2 vs -15.4; Δ = -3.8; 95% CI, -9.2 to 1.6; P = .17). During the 29-day treatment, treatment-related adverse events were reported in 15 participants (14.6%) in the cyclosporine group and 11 participants (10.7%) in the vehicle group.Conclusions and relevanceResults demonstrated superiority of a water-free cyclosporine, 0.1%, eye solution over vehicle in improving tCFS score at day 29 in Chinese participants with DED. However, dryness score (VAS) was not improved at day 29.Trial registrationClinicalTrials.gov Identifier: NCT05841043.

Dataset Information

A Phase 2 Trial to Test Safety and Efficacy of ST-100, a Unique Collagen Mimetic Peptide Ophthalmic Solution for Dry Eye Disease.

Objective

Design

Participants

Intervention

Main outcome measures

Results

Conclusions

Financial disclosures

Publications

A Phase 2 Trial to Test Safety and Efficacy of ST-100, a Unique Collagen Mimetic Peptide Ophthalmic Solution for Dry Eye Disease.

Similar Datasets

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