Dataset Information

Phase 1 Study of THR-687, a Novel, Highly Potent Integrin Antagonist for the Treatment of Diabetic Macular Edema.

ABSTRACT:

Purpose

To evaluate the safety and preliminary efficacy of THR-687 in patients with center-involved diabetic macular edema (DME).

Design

Phase 1, open-label, multicenter, 3 + 3 dose-escalation study with 3-month follow-up.

Participants

Patients 18 years of age or older with visual impairment resulting from DME.

Methods

Single intravitreal injection of THR-687 (0.4 mg, 1.0 mg, or 2.5 mg).

Main outcome measures

The primary outcome measure was the incidence of dose-limiting toxicities (DLTs). The secondary outcome measure was the incidence of adverse events (AEs), including the occurrence of laboratory abnormalities. Exploratory outcome measures included changes from baseline in best-corrected visual acuity (BCVA) and central subfield thickness (CST), assessments of ischemia and leakage on fluorescein angiography, and THR-687 levels in plasma.

Results

Twelve patients were treated: 3 patients received 0.4 mg of THR-687, 3 patients received 1.0 mg of THR-687, and 6 patients received 2.5 mg of THR-687. Most patients were men (9/12 patients). Their mean age was 57.8 years. No DLTs or serious AEs were reported at any of the dose levels tested. Overall, 9 AEs in the study eye were reported for 5 of 12 patients. Of those, 4 AEs in 3 of 12 patients were deemed treatment related by the investigator, all of which were mild, started on the day of the injection, and had resolved within 28 days without treatment. Overall, mean gains from baseline in BCVA were observed at all study visits with a rapid onset (7.2 Early Treatment Diabetic Retinopathy Study [ETDRS] letters at day 7) and a durability up to the end of the study (8.3 ETDRS letters at month 3). A mean decrease in CST was observed up to month 1. Overall, the mean BCVA gains and CST decreases were highest at the highest THR-687 dose level tested. THR-687 was undetectable in plasma at 7 days after the injection.

Conclusions

At all dose levels tested, a single intravitreal injection of THR-687 was safe and well tolerated. Preliminary efficacy was observed by a rapid gain in BCVA with 3 months' durability and a decrease in CST up to 1 month after the injection.

SUBMITTER: Khanani AM

PROVIDER: S-EPMC9562295 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Publications

Phase 1 Study of THR-687, a Novel, Highly Potent Integrin Antagonist for the Treatment of Diabetic Macular Edema.

Khanani Arshad M AM Patel Sunil S SS Gonzalez Victor H VH Moon Suk J SJ Jaffe Glenn J GJ Wells John A JA Kozma Petra P Dugel Pravin U PU Maturi Raj K RK

Ophthalmology science 20210714 3

<h4>Purpose</h4>To evaluate the safety and preliminary efficacy of THR-687 in patients with center-involved diabetic macular edema (DME).<h4>Design</h4>Phase 1, open-label, multicenter, 3 + 3 dose-escalation study with 3-month follow-up.<h4>Participants</h4>Patients 18 years of age or older with visual impairment resulting from DME.<h4>Methods</h4>Single intravitreal injection of THR-687 (0.4 mg, 1.0 mg, or 2.5 mg).<h4>Main outcome measures</h4>The primary outcome measure was the incidence of do ...[more]

PMID: 36247818

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Project description:ObjectiveTo provide data on the short-term effect of intravitreal bevacizumab for diabetic macular edema (DME).DesignRandomized phase II clinical trial.ParticipantsOne hundred twenty-one eyes of 121 subjects (109 eligible for analysis) with DME and Snellen acuity equivalent ranging from 20/32 to 20/320.InterventionsRandom assignment to 1 of 5 groups: (A) focal photocoagulation at baseline (n = 19), (B) intravitreal injection of 1.25 mg of bevacizumab at baseline and 6 weeks (n = 22), (C) intravitreal injection of 2.5 mg of bevacizumab at baseline and 6 weeks (n = 24), (D) intravitreal injection of 1.25 mg of bevacizumab at baseline and sham injection at 6 weeks (n = 22), or (E) intravitreal injection of 1.25 mg of bevacizumab at baseline and 6 weeks with photocoagulation at 3 weeks (n = 22).Main outcome measuresCentral subfield thickness (CST) on optical coherence tomography and best-corrected visual acuity (VA) were measured at baseline and after 3, 6, 9, 12, 18, and 24 weeks.ResultsAt baseline, median CST was 411 mum and median Snellen VA equivalent was 20/50. Compared with group A, groups B and C had a greater reduction in CST at 3 weeks and about 1 line better median VA over 12 weeks. There were no meaningful differences between groups B and C in CST reduction or VA improvement. A CST reduction > 11% (reliability limit) was present at 3 weeks in 36 of 84 (43%) bevacizumab-treated eyes and 5 of 18 (28%) eyes treated with laser alone, and at 6 weeks in 31 of 84 (37%) and 9 of 18 (50%) eyes, respectively. Combining focal photocoagulation with bevacizumab resulted in no apparent short-term benefit or adverse outcomes. Endophthalmitis developed in 1 eye. The following events occurred during the first 24 weeks in subjects treated with bevacizumab without attributing cause to the drug: myocardial infarction (n = 2), congestive heart failure (n = 1), elevated blood pressure (n = 3), and worsened renal function (n = 3).ConclusionThese results demonstrate that intravitreal bevacizumab can reduce DME in some eyes, but the study was not designed to determine whether treatment is beneficial. A phase III trial would be needed for that purpose.

Dataset Information

Phase 1 Study of THR-687, a Novel, Highly Potent Integrin Antagonist for the Treatment of Diabetic Macular Edema.

Purpose

Design

Participants

Methods

Main outcome measures

Results

Conclusions

Publications

Phase 1 Study of THR-687, a Novel, Highly Potent Integrin Antagonist for the Treatment of Diabetic Macular Edema.

Similar Datasets

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