PROMINENT-Eye Ancillary Study (Protocol AD)

NCT ID: NCT03345901

Last Updated: 2020-09-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-15
• Study Completion Date: 2019-04-03

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.

Conditions

Diabetic Retinopathy; Diabetic Macular Edema

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Pemafibrate

.2 mg pemafibrate orally BID

Group Type: EXPERIMENTAL

Pemafibrate

Intervention Type: DRUG

0.2 mg orally BID - twice daily

Placebo

Placebo pill orally BID

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

orally BID - twice daily

Interventions

Pemafibrate

0.2 mg orally BID - twice daily

Intervention Type: DRUG

Placebo

orally BID - twice daily

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Already randomized at US or Canadian sites in the PROMINENT study
• Ability to cooperate with dilated ophthalmic examination and imaging procedures

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kowa Company, Ltd.

INDUSTRY

Sponsor Role: collaborator

Jaeb Center for Health Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Emily Chew, MD

Role: STUDY_CHAIR

National Eye Institute (NEI)

Locations

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

Florida Retina Consultants

Lakeland, Florida, United States

Retina Macula Specialists of Miami

Miami, Florida, United States

Florida Retina Institute

Orlando, Florida, United States

Southeast Eye Institute, P.A. dba Eye Associates of Pinellas

Pinellas Park, Florida, United States

Sarasota Retina Institute

Sarasota, Florida, United States

Emory Eye Center

Atlanta, Georgia, United States

Emory Eye Center

Atlanta, Georgia, United States

Southeast Retina Center, P.C.

Augusta, Georgia, United States

Thomas Eye Group

Sandy Springs, Georgia, United States

Northwestern Medical Faculty Foundation

Chicago, Illinois, United States

Northwestern Medical Faculty Foundation

Chicago, Illinois, United States

University of Illinois at Chicago Medical Center

Chicago, Illinois, United States

NorthShore University HealthSystem

Glenview, Illinois, United States

Illinois Retina Associates, S.C.

Oak Park, Illinois, United States

John-Kenyon American Eye Institute

New Albany, Indiana, United States

Wolfe Eye Clinic

West Des Moines, Iowa, United States

Mid-America Retina Consultants, P.A.

Overland Park, Kansas, United States

Retina Associates, P.A.

Shawnee Mission, Kansas, United States

Retina and Vitreous Associates of Kentucky

Lexington, Kentucky, United States

Eye Associates of Northeast Louisiana dba Haik Humble Eye Center

West Monroe, Louisiana, United States

Eye Associates of Northeast Louisiana dba Haik Humble Eye Center

West Monroe, Louisiana, United States

Elman Retina Group, P.A.

Baltimore, Maryland, United States

Wilmer Eye Institute at Johns Hopkins

Baltimore, Maryland, United States

Valley Eye Physicians and Surgeons

Ayer, Massachusetts, United States

Ophthalmic Consultants of Boston

Boston, Massachusetts, United States

Joslin Diabetes Center

Boston, Massachusetts, United States

Kellogg Eye Center, University of Michigan

Ann Arbor, Michigan, United States

Henry Ford Health System, Dept of Ophthalmology and Eye Care Services

Detroit, Michigan, United States

Henry Ford Health System, Dept of Ophthalmology and Eye Care Services

Detroit, Michigan, United States

Vitreo-Retinal Associates

Grand Rapids, Michigan, United States

Retina Center, PA

Minneapolis, Minnesota, United States

Retina Center, PA

Minneapolis, Minnesota, United States

The Retina Institute

St Louis, Missouri, United States

Eye Associates of New Mexico

Albuquerque, New Mexico, United States

Eye Associates of New Mexico

Albuquerque, New Mexico, United States

MaculaCare

New York, New York, United States

Retina Associates of Western New York

Rochester, New York, United States

Retina-Vitreous Surgeons of Central New York, PC

Syracuse, New York, United States

Western Carolina Clinical Research, LLC

Asheville, North Carolina, United States

Kittner Eye Center

Chapel Hill, North Carolina, United States

Kittner Eye Center

Chapel Hill, North Carolina, United States

Charlotte Eye, Ear, Nose and Throat Assoc., PA

Charlotte, North Carolina, United States

Retina Vitreous Center

Edmond, Oklahoma, United States

Dean A. McGee Eye Institute

Oklahoma City, Oklahoma, United States

Retina Vitreous Consultants

Monroeville, Pennsylvania, United States

Southeastern Retina Associates

Chattanooga, Tennessee, United States

Southeastern Retina Associates, P.C.

Knoxville, Tennessee, United States

Retina Research Center

Austin, Texas, United States

Robert E. Torti, MD, PA dba Retina Specialists

DeSoto, Texas, United States

Valley Retina Institute

DeSoto, Texas, United States

Retina Center of Texas

Grapevine, Texas, United States

Baylor Eye Physicians and Surgeons

Houston, Texas, United States

Baylor Eye Physicians and Surgeons

Houston, Texas, United States

Retina Consultants of Houston, PA

Houston, Texas, United States

Valley Retina Institute

McAllen, Texas, United States

Medical Center Ophthalmology Associates

San Antonio, Texas, United States

Retinal Consultants of San Antonio

San Antonio, Texas, United States

Retina Institute of Virginia

Richmond, Virginia, United States

University of Wisconsin-Madison, Dept of Ophthalmology/Retina Service

Madison, Wisconsin, United States

UBC/VCHA Eye Care Centre

Vancouver, British Columbia, Canada

University Health Network - Toronto Western Hospital

Toronto, , Canada

Countries

United States; Canada

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

DRCR.net Protocol AD

Identifier Type: -

Identifier Source: org_study_id