PROMINENT-Eye Ancillary Study (Protocol AD)

PROMINENT-Eye Ancillary Study: Diabetic Retinopathy Outcomes in a Randomized Trial of Pemafibrate Versus Placebo (Protocol AD)

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.

Study Overview

• Status: Terminated
• Conditions: Diabetic Retinopathy; Diabetic Macular Edema
• Intervention / Treatment: Drug: Pemafibrate; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Toronto, Canada, M5T 2S8
    • University Health Network - Toronto Western Hospital
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 3N9
      • UBC/VCHA Eye Care Centre
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85021
      • Arizona Retina and Vitreous Consultants
  • California
    • Campbell, California, United States, 95008
      • Retinal Diagnostic Center
    • Glendale, California, United States, 91203
      • Macula & Retina Institute
    • Huntington Beach, California, United States, 92647
      • Atlantis Eye Care
    • Loma Linda, California, United States, 92354
      • Loma Linda University Health Care, Department of Ophthalmology
    • Long Beach, California, United States, 90807
      • South Coast Retina Center
    • Mountain View, California, United States, 94040
      • Northern California Retina Vitreous Associates
    • Westlake Village, California, United States, 91361
      • Retinal Consultants of Southern California Medical Group, Inc.
  • Florida
    • Fort Myers, Florida, United States, 33912
      • National Ophthalmic Research Institute
    • Jacksonville, Florida, United States, 32209
      • University of Florida College of Med., Department of Ophthalmology, Jacksonville Health Science Cent
    • Lakeland, Florida, United States, 33805
      • Florida Retina Consultants
    • Miami, Florida, United States, 33126
      • Retina Macula Specialists Of Miami
    • Orlando, Florida, United States, 32806
      • Florida Retina Institute
    • Pinellas Park, Florida, United States, 33782
      • Southeast Eye Institute, P.A. dba Eye Associates of Pinellas
    • Sarasota, Florida, United States, 34239
      • Sarasota Retina Institute
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory Eye Center
    • Atlanta, Georgia, United States, 30322-1013
      • Emory Eye Center
    • Augusta, Georgia, United States, 30909
      • Southeast Retina Center, P.C.
    • Sandy Springs, Georgia, United States, 30328
      • Thomas Eye Group
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Medical Faculty Foundation
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago Medical Center
    • Chicago, Illinois, United States, 60611-2987
      • Northwestern Medical Faculty Foundation
    • Glenview, Illinois, United States, 60026
      • Northshore University Healthsystem
    • Oak Park, Illinois, United States, 60304
      • Illinois Retina Associates, S.C.
  • Indiana
    • New Albany, Indiana, United States, 47150
      • John-Kenyon American Eye Institute
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • Wolfe Eye Clinic
  • Kansas
    • Overland Park, Kansas, United States, 66211
      • Mid-America Retina Consultants, P.A.
    • Shawnee Mission, Kansas, United States, 66204
      • Retina Associates, P.A.
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Retina and Vitreous Associates of Kentucky
  • Louisiana
    • West Monroe, Louisiana, United States, 71291-4452
      • Eye Associates of Northeast Louisiana dba Haik Humble Eye Center
    • West Monroe, Louisiana, United States, 71291
      • Eye Associates of Northeast Louisiana dba Haik Humble Eye Center
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Elman Retina Group, P.A.
    • Baltimore, Maryland, United States, 21287
      • Wilmer Eye Institute at Johns Hopkins
  • Massachusetts
    • Ayer, Massachusetts, United States, 01432
      • Valley Eye Physicians and Surgeons
    • Boston, Massachusetts, United States, 02215
      • Joslin Diabetes Center
    • Boston, Massachusetts, United States, 02114
      • Ophthalmic Consultants of Boston
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • Kellogg Eye Center, University of Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System, Dept of Ophthalmology and Eye Care Services
    • Detroit, Michigan, United States, 48202-2689
      • Henry Ford Health System, Dept of Ophthalmology and Eye Care Services
    • Grand Rapids, Michigan, United States, 49546
      • Vitreo-Retinal Associates
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Retina Center, PA
    • Minneapolis, Minnesota, United States, 34239
      • Retina Center, PA
  • Missouri
    • Saint Louis, Missouri, United States, 63128
      • The Retina Institute
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Eye Associates of New Mexico
    • Albuquerque, New Mexico, United States, 87109-5857
      • Eye Associates of New Mexico
  • New York
    • New York, New York, United States, 10021
      • MaculaCare
    • Rochester, New York, United States, 14620
      • Retina Associates of Western New York
    • Syracuse, New York, United States, 13224
      • Retina-Vitreous Surgeons of Central New York, PC
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Western Carolina Clinical Research, LLC
    • Chapel Hill, North Carolina, United States, 27517
      • Kittner Eye Center
    • Chapel Hill, North Carolina, United States, 27517-8923
      • Kittner Eye Center
    • Charlotte, North Carolina, United States, 28210
      • Charlotte Eye, Ear, Nose and Throat Assoc., PA
  • Oklahoma
    • Edmond, Oklahoma, United States, 73103
      • Retina Vitreous Center
    • Oklahoma City, Oklahoma, United States, 73104
      • Dean A. McGee Eye Institute
  • Pennsylvania
    • Monroeville, Pennsylvania, United States, 15146
      • Retina Vitreous Consultants
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • Southeastern Retina Associates
    • Knoxville, Tennessee, United States, 37909
      • Southeastern Retina Associates, P.C.
  • Texas
    • Austin, Texas, United States, 78705
      • Retina Research Center
    • DeSoto, Texas, United States, 75115-2011
      • Robert E. Torti, MD, PA dba Retina Specialists
    • DeSoto, Texas, United States, 75115
      • Valley Retina Institute
    • Grapevine, Texas, United States, 76051
      • Retina Center of Texas
    • Houston, Texas, United States, 77030
      • Retina Consultants of Houston, PA
    • Houston, Texas, United States, 77030
      • Baylor Eye Physicians and Surgeons
    • Houston, Texas, United States, 77030-4101
      • Baylor Eye Physicians and Surgeons
    • McAllen, Texas, United States, 78503
      • Valley Retina Institute
    • San Antonio, Texas, United States, 78240
      • Medical Center Ophthalmology Associates
    • San Antonio, Texas, United States, 78240
      • Retinal Consultants of San Antonio
  • Virginia
    • Richmond, Virginia, United States, 23235
      • Retina Institute of Virginia
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin-Madison, Dept of Ophthalmology/Retina Service

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pemafibrate; .2 mg pemafibrate orally BID	Drug: Pemafibrate; 0.2 mg orally BID - twice daily
Placebo Comparator: Placebo; Placebo pill orally BID	Drug: Placebo; orally BID - twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Diabetic Retinopathy Worsening or Diabetic Macular Edema (DME) Development (Composite Outcome)	4 years

Collaborators and Investigators

• Sponsor: Jaeb Center for Health Research
• Collaborators: Kowa Company, Ltd.
• Investigators: Study Chair: Emily Chew, MD, National Eye Institute (NEI)

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2018
• Primary Completion (Actual): April 3, 2019
• Study Completion (Actual): April 3, 2019

Study Registration Dates

• First Submitted: November 7, 2017
• First Submitted That Met QC Criteria: November 14, 2017
• First Posted (Actual): November 17, 2017

Study Record Updates

• Last Update Posted (Actual): September 16, 2020
• Last Update Submitted That Met QC Criteria: August 27, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: pemafibrate
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Endocrine System Diseases; Diabetic Angiopathies; Diabetes Complications; Diabetes Mellitus; Retinal Degeneration; Macular Degeneration; Retinal Diseases; Diabetic Retinopathy; Macular Edema
• Other Study ID Numbers: DRCR.net Protocol AD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Data related to the eye ancillary study will be made available after completion of the study and publication of the outcome manuscript.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No