PROMINENT-Eye Ancillary Study (Protocol AD)

Phase 3

Terminated

Conditions: Diabetic Retinopathy
Diabetic Macular Edema

Interventions: Drug: Placebo
Drug: Pemafibrate

Registration Number: NCT03345901

Lead Sponsor: Jaeb Center for Health Research

Brief Summary: Despite improved glycemic and systemic control for many patients with diabetes, over the past several decades, diabetic retinopathy (DR) develops and progresses in a large proportion of patients, and visual loss from diabetic eye complications continues to be a leading cause of blindness in the US and other developed countries worldwide. Thus, even a modest ability to prevent DR onset or to slow DR worsening might substantially reduce the number of patients at risk for diabetes-related vision loss worldwide. Widespread use of an oral agent effective at reducing worsening of DR might also decrease the numbers of patients who undergo treatment for DR and diabetic macular edema (DME) and who are consequently at risk for side effects that adversely affect visual function. Two major studies of fenofibrate, the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) and The Action to Control Cardiovascular Risk in Diabetes (ACCORD)-eye study, have demonstrated clinically important reduction in progression of retinopathy in patients with diabetes assigned to fibrate compared with placebo. However, despite the positive clinical trial results, fenofibrate has not gained wide acceptance as a preventive agent by either ophthalmologists or primary diabetes care providers. Thus, it is important to provide further evidence demonstrating whether or not selectively increasing peroxisome proliferator-activated receptor alpha (PPARα) activity reduces progression of retinopathy in patients with diabetes and non-proliferative diabetic retinopathy at baseline. Pemafibrate is a more potent and selective PPARα modulator than fenofibrate. Its efficacy is currently being evaluated in the Pemafibrate to Reduce Cardiovascular OutcoMes by Reducing Triglycerides IN patiENts With diabeTes (PROMINENT) study for prevention of cardiovascular events in patients with type 2 diabetes. Given the large study cohort with a substantial proportion likely to have DR and the multi-year duration of the PROMINENT trial, this study represents a unique opportunity to assess effects of chronic PPARα activation through pemafibrate therapy on DR outcomes.

Primary Study Objective: To assess whether treatment with pemafibrate (0.2 mg orally BID) compared with placebo reduces the hazard rate of diabetic retinopathy worsening in adults with type 2 diabetes and diabetic retinopathy without neovascularization in at least one eye who are participating in the parent PROMINENT trial.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 18

Inclusion Criteria

Already randomized at US or Canadian sites in the PROMINENT study
Ability to cooperate with dilated ophthalmic examination and imaging procedures
At least one eye meets the following study eye inclusion criteria:
1. Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity level between 20 and 53 (minimal to severe non-proliferative diabetic retinopathy (NPDR)), inclusive, on color fundus photographs confirmed by central Reading Center grading.

Exclusion Criteria

Study eye exclusion criteria are:

a. Neovascularization present. b. Current central-involved diabetic macular edema (DME based on optical coherence tomography (OCT) central subfield thickness (CST) i. Zeiss Cirrus: CST ≥ 290µm in women or ≥ 305µm in men ii. Heidelberg Spectralis: CST ≥ 305µm in women or ≥ 320µm in men c. Known major non-diabetic intraocular pathology that in the opinion of the investigator would substantially and adversely affect visual acuity or lead to ocular neovascularization during the course of the study d. Anticipated need for intravitreous anti-vascular endothelial growth factor (VEGF), intravitreous corticosteroid, or pan-retinal photocoagulation (PRP) in the next 6 months following randomization e. History of intravitreous anti-VEGF or corticosteroid treatment within the prior year for any indication.

f. History of intraocular surgery within prior 4 months or anticipated within the next 6 months following randomization g. Any history of PRP or vitrectomy h. History of yttrium aluminum garnet (YAG) capsulotomy performed within 2 months prior to screening i. Aphakia j. Known substantial media opacities that would preclude successful imaging

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo pill orally BID
Pemafibrate	Pemafibrate	.2 mg pemafibrate orally BID

Primary Outcome Measures

Name	Time	Method
Diabetic Retinopathy Worsening or Diabetic Macular Edema (DME) Development (Composite Outcome)	4 years

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (62): Arizona Retina and Vitreous Consultants
🇺🇸
Phoenix, Arizona, United States
Retinal Diagnostic Center
🇺🇸
Campbell, California, United States
Macula & Retina Institute
🇺🇸
Glendale, California, United States
Atlantis Eye Care
🇺🇸
Huntington Beach, California, United States
Loma Linda University Health Care, Department of Ophthalmology
🇺🇸
Loma Linda, California, United States
South Coast Retina Center
🇺🇸
Long Beach, California, United States
Northern California Retina Vitreous Associates
🇺🇸
Mountain View, California, United States
Retinal Consultants of Southern California Medical Group, Inc.
🇺🇸
Westlake Village, California, United States
National Ophthalmic Research Institute
🇺🇸
Fort Myers, Florida, United States
University of Florida College of Med., Department of Ophthalmology, Jacksonville Health Science Cent
🇺🇸
Jacksonville, Florida, United States
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Arizona Retina and Vitreous Consultants
🇺🇸Phoenix, Arizona, United States