Clinical trial NCT05727891: Evaluation of Tonabersat for DME
Official title: A Phase 2 Evaluation of Tonabersat for Diabetic Macular Edema (Protocol AN)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Diabetic Macular Edema
Lead sponsor: Jaeb Center for Health Research
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Eye Institute (NEI)
name: Juvenile Diabetes Research Foundation
First posted: 2023-02-14
Enrollment: 128
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-masked, placebo-controlled clinical trial
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: Key Inclusion Criteria

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

   * Best corrected E-ETDRS visual acuity letter score ≥ 74 (i.e., 20/32 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 anti-VEGF injections within prior 3 years
* 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

Primary outcomes:
measure: Mean change in central subfield thickness
timeFrame: 6 months
Secondary outcomes:
measure: Mean change in retinal volume from baseline
timeFrame: 6 months
measure: Percentage of eyes central subfield thickness below optical coherence machine- and sex-specific threshold for DME and at least a 10% decrease from baseline
timeFrame: 6 months
measure: Mean change in visual acuity from baseline
timeFrame: 6 months
measure: Percentage of eyes receiving other treatment for DME prior to the 6 month visit
timeFrame: 6 months
Other outcomes:
Locations:
city: Huntington Beach
country: United States
facility: Retina Associates of Southern California
state: California
city: Loma Linda
country: United States
facility: Loma Linda University
state: California
city: Oakland
country: United States
facility: East Bay Retina Consultants, Inc.
state: California
city: Palm Desert
country: United States
facility: Southern California Desert Retina Consultants, Inc.
state: California
city: Torrance
country: United States
facility: Macula Retina Vitreous Institute
state: California
city: Fort Myers
country: United States
facility: National Ophthalmic Research Institute
state: Florida
city: Jacksonville
country: United States
facility: University of Florida- Jacksonville
state: Florida
city: Lakeland
country: United States
facility: Central Florida Retina Institute
state: Florida
city: Lakeland
country: United States
facility: Florida Retina Consultants
state: Florida
city: Pinellas Park
country: United States
facility: Southeast Eye Institute, P.A. dba Eye Associates of Pinellas
state: Florida
city: Augusta
country: United States
facility: Southeast Retina Center
state: Georgia
city: Sandy Springs
country: United States
facility: Thomas Eye Group
state: Georgia
city: Oak Park
country: United States
facility: Illinois Retina Associates
state: Illinois
city: Indianapolis
country: United States
facility: Midwest Eye Institute
state: Indiana
city: West Monroe
country: United States
facility: Joseph E. Humble and Raymond Haik PTRS DBA Eye Assoc of Northeast Louisiana
state: Louisiana
city: Baltimore
country: United States
facility: Elman Retina Group
state: Maryland
city: Boston
country: United States
facility: Boston Medical Center Corporation
state: Massachusetts
city: Boston
country: United States
facility: Joslin Diabetes Center
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Retina Research Institute, LLC
state: Missouri
city: Liverpool
country: United States
facility: Retina-Vitreous Surgeons of Central NY, PC
state: New York
city: Eugene
country: United States
facility: Verum Research LLC
state: Oregon
city: Philadelphia
country: United States
facility: The Trustees of the University of Pennsylvania
state: Pennsylvania
city: Sewickley
country: United States
facility: Pittsburg Clinical Trial Consortium
state: Pennsylvania
city: Hilton Head Island
country: United States
facility: Hilton Head Retina Institute
state: South Carolina
city: Bellaire
country: United States
facility: Retina Consultants of Texas, PA
state: Texas
city: Lubbock
country: United States
facility: Texas Retina Associates
state: Texas
city: San Antonio
country: United States
facility: Retinal Consultants of Texas
state: Texas
Study officials:
References: