AN: A Phase 2 Evaluation of Tonabersat for DME

Study Details

Study Description

Brief Summary

This randomized clinical trial will evaluate the effect of tonabersat compared with placebo on central subfield thickness (CST) in eyes with center-involved diabetic macular edema (CI-DME) and good visual acuity.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Macular Edema	Drug: Tonabersat Other: Placebo	Phase 2

Detailed Description

The primary objective is to assess the effects of tonabersat, an orally administered Connexin43 hemichannel inhibitor, on central subfield thickness (mean change) compared with placebo in eyes with CI-DME and good visual acuity at 6 months.

Exploratory objectives will evaluate biomarkers of kidney function for potential benefit. Furthermore, this phase 2 study is being conducted to determine whether the conduct of a phase 3 trial has merit and provide information on outcome measures needed to design a phase 3 trial.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

128 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized, double-masked, placebo-controlled clinical trialRandomized, double-masked, placebo-controlled clinical trial

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Phase 2 Evaluation of Tonabersat for Diabetic Macular Edema (Protocol AN)

Anticipated Study Start Date :

Mar 1, 2023

Anticipated Primary Completion Date :

Sep 1, 2024

Anticipated Study Completion Date :

Mar 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo	Other: Placebo One pill of Study Drug (placebo) is taken orally once daily. It is recommended the Study Drug be taken in the evening without food, but it may be taken at an alternate time with or without food. The first dose (one pill) will be taken in the office, regardless of the time of day.
Active Comparator: Tonabersat (40 mg)	Drug: Tonabersat One pill of Study Drug (40 mg tonabersat) is taken orally once daily. It is recommended the Study Drug be taken in the evening without food, but it may be taken at an alternate time with or without food. The first dose (one pill) will be taken in the office, regardless of the time of day.

Arm

Intervention/Treatment

Placebo Comparator: Placebo

Other: Placebo

One pill of Study Drug (placebo) is taken orally once daily. It is recommended the Study Drug be taken in the evening without food, but it may be taken at an alternate time with or without food. The first dose (one pill) will be taken in the office, regardless of the time of day.

Active Comparator: Tonabersat (40 mg)

Drug: Tonabersat

One pill of Study Drug (40 mg tonabersat) is taken orally once daily. It is recommended the Study Drug be taken in the evening without food, but it may be taken at an alternate time with or without food. The first dose (one pill) will be taken in the office, regardless of the time of day.

Outcome Measures

Primary Outcome Measures

Mean change in central subfield thickness [6 months]

Secondary Outcome Measures

Mean change in retinal volume from baseline [6 months]
Percentage of eyes central subfield thickness below optical coherence machine- and gender-specific threshold for DME and at least a 10% decrease from baseline [6 months]
Composite outcome, gender-specific spectral domain optical coherence tomography equivalent of 250 µm on Zeiss Stratus optical coherence tomography
Mean change in visual acuity from baseline [6 months]
Percentage of eyes receiving other treatment for DME [6 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria

Adults with type 1 or 2 diabetes mellitus
At least one eye with:

Best corrected E-ETDRS visual acuity letter score ≥ 79 (i.e., 20/25 or better)
Ophthalmoscopic evidence of center-involved DME in study eye confirmed by central subfield thickness on spectral domain OCT

Zeiss Cirrus: ≥ 290 µm in females, ≥ 305 µm in males
Heidelberg Spectralis: ≥ 305 µm in females, ≥ 320 µm in males Recruitment will be monitored with a goal to have equal proportions in the following categories above the CI-DME thresholds: <75 μm, 75 μm to <175 μm, ≥175 μm 3. Media clarity, pupillary dilation, and study participant cooperation sufficient for adequate OCT Key Exclusion Criteria
Macular edema is considered to be due to a cause other than DME
Major ocular surgery within prior 4 months, or anticipated after randomization
History of focal/grid laser or other ocular surgical, intravitreal, or peribulbar treatment for DR or DME within prior 1 year, and no more than 4 prior anti-VEGF injections total
Anticipated need to treat DME or DR during the first 6 months, or anticipated need for cataract surgery during study period
Any history of vitrectomy
Systemic anti-VEGF or pro-VEGF treatment within 12 months prior to randomization
History of chronic renal failure requiring dialysis or kidney transplant
History of moderate to severe hepatic impairment, including known liver function test (LFT) values > 3x's the upper limit of normal

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Jaeb Center for Health Research
National Institutes of Health (NIH)
National Eye Institute (NEI)
Juvenile Diabetes Research Foundation

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Jaeb Center for Health Research

ClinicalTrials.gov Identifier:

NCT05727891

Other Study ID Numbers:

DRCR Protocol AN

First Posted:

Feb 14, 2023

Last Update Posted:

Feb 14, 2023

Last Verified:

Feb 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Macular Edema

Study Results

No Results Posted as of Feb 14, 2023