PROMINENT-Eye Ancillary Study (Protocol AD)

NCT03345901 | Terminated Phase 3 Results FDA Drug

• 1 other identifier: DRCR.net Protocol AD
• Study Type: interventional
• Target: 18
• Locations: 2 countries
• Sites: 71

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

Keywords

pemafibrate

Outcome Measures

Primary Outcomes (1)

• Diabetic Retinopathy Worsening or Diabetic Macular Edema (DME) Development (Composite Outcome)

  4 years

Study Arms (2)

Pemafibrate

EXPERIMENTAL

.2 mg pemafibrate orally BID

Drug: Pemafibrate

Placebo

PLACEBO COMPARATOR

Placebo pill orally BID

Drug: Placebo

Interventions

Pemafibrate DRUG

0.2 mg orally BID - twice daily

Pemafibrate

Placebo DRUG

orally BID - twice daily

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Jaeb Center for Health Research: lead
• Kowa Company, Ltd.: collaborator

Study Sites (71)

Arizona Retina and Vitreous Consultants

Phoenix, Arizona, 85021, United States

Location

Retinal Diagnostic Center

Campbell, California, 95008, United States

Location

Macula & Retina Institute

Glendale, California, 91203, United States

Location

Atlantis Eye Care

Huntington Beach, California, 92647, United States

Location

Loma Linda University Health Care, Department of Ophthalmology

Loma Linda, California, 92354, United States

Location

South Coast Retina Center

Long Beach, California, 90807, United States

Location

Northern California Retina Vitreous Associates

Mountain View, California, 94040, United States

Location

Retinal Consultants of Southern California Medical Group, Inc.

Westlake Village, California, 91361, United States

Location

National Ophthalmic Research Institute

Fort Myers, Florida, 33912, United States

Location

University of Florida College of Med., Department of Ophthalmology, Jacksonville Health Science Cent

Jacksonville, Florida, 32209, United States

Location

Florida Retina Consultants

Lakeland, Florida, 33805, United States

Location

Retina Macula Specialists of Miami

Miami, Florida, 33126, United States

Location

Florida Retina Institute

Orlando, Florida, 32806, United States

Location

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

Pinellas Park, Florida, 33782, United States

Location

Sarasota Retina Institute

Sarasota, Florida, 34239, United States

Location

Emory Eye Center

Atlanta, Georgia, 30322-1013, United States

Location

Emory Eye Center

Atlanta, Georgia, 30322, United States

Location

Southeast Retina Center, P.C.

Augusta, Georgia, 30909, United States

Location

Thomas Eye Group

Sandy Springs, Georgia, 30328, United States

Location

Northwestern Medical Faculty Foundation

Chicago, Illinois, 60611-2987, United States

Location

Northwestern Medical Faculty Foundation

Chicago, Illinois, 60611, United States

Location

University of Illinois at Chicago Medical Center

Chicago, Illinois, 60612, United States

Location

NorthShore University HealthSystem

Glenview, Illinois, 60026, United States

Location

Illinois Retina Associates, S.C.

Oak Park, Illinois, 60304, United States

Location

John-Kenyon American Eye Institute

New Albany, Indiana, 47150, United States

Location

Wolfe Eye Clinic

West Des Moines, Iowa, 50266, United States

Location

Mid-America Retina Consultants, P.A.

Overland Park, Kansas, 66211, United States

Location

Retina Associates, P.A.

Shawnee Mission, Kansas, 66204, United States

Location

Retina and Vitreous Associates of Kentucky

Lexington, Kentucky, 40509, United States

Location

Eye Associates of Northeast Louisiana dba Haik Humble Eye Center

West Monroe, Louisiana, 71291-4452, United States

Location

Eye Associates of Northeast Louisiana dba Haik Humble Eye Center

West Monroe, Louisiana, 71291, United States

Location

Elman Retina Group, P.A.

Baltimore, Maryland, 21237, United States

Location

Wilmer Eye Institute at Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

Valley Eye Physicians and Surgeons

Ayer, Massachusetts, 01432, United States

Location

Ophthalmic Consultants of Boston

Boston, Massachusetts, 02114, United States

Location

Joslin Diabetes Center

Boston, Massachusetts, 02215, United States

Location

Kellogg Eye Center, University of Michigan

Ann Arbor, Michigan, 48105, United States

Location

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

Detroit, Michigan, 48202-2689, United States

Location

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

Detroit, Michigan, 48202, United States

Location

Vitreo-Retinal Associates

Grand Rapids, Michigan, 49546, United States

Location

Retina Center, PA

Minneapolis, Minnesota, 34239, United States

Location

Retina Center, PA

Minneapolis, Minnesota, 55404, United States

Location

The Retina Institute

St Louis, Missouri, 63128, United States

Location

Eye Associates of New Mexico

Albuquerque, New Mexico, 87109-5857, United States

Location

Eye Associates of New Mexico

Albuquerque, New Mexico, 87109, United States

Location

MaculaCare

New York, New York, 10021, United States

Location

Retina Associates of Western New York

Rochester, New York, 14620, United States

Location

Retina-Vitreous Surgeons of Central New York, PC

Syracuse, New York, 13224, United States

Location

Western Carolina Clinical Research, LLC

Asheville, North Carolina, 28803, United States

Location

Kittner Eye Center

Chapel Hill, North Carolina, 27517-8923, United States

Location

Kittner Eye Center

Chapel Hill, North Carolina, 27517, United States

Location

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

Charlotte, North Carolina, 28210, United States

Location

Retina Vitreous Center

Edmond, Oklahoma, 73103, United States

Location

Dean A. McGee Eye Institute

Oklahoma City, Oklahoma, 73104, United States

Location

Retina Vitreous Consultants

Monroeville, Pennsylvania, 15146, United States

Location

Southeastern Retina Associates

Chattanooga, Tennessee, 37421, United States

Location

Southeastern Retina Associates, P.C.

Knoxville, Tennessee, 37909, United States

Location

Retina Research Center

Austin, Texas, 78705, United States

Location

Robert E. Torti, MD, PA dba Retina Specialists

DeSoto, Texas, 75115-2011, United States

Location

Valley Retina Institute

DeSoto, Texas, 75115, United States

Location

Retina Center of Texas

Grapevine, Texas, 76051, United States

Location

Baylor Eye Physicians and Surgeons

Houston, Texas, 77030-4101, United States

Location

Baylor Eye Physicians and Surgeons

Houston, Texas, 77030, United States

Location

Retina Consultants of Houston, PA

Houston, Texas, 77030, United States

Location

Valley Retina Institute

McAllen, Texas, 78503, United States

Location

Medical Center Ophthalmology Associates

San Antonio, Texas, 78240, United States

Location

Retinal Consultants of San Antonio

San Antonio, Texas, 78240, United States

Location

Retina Institute of Virginia

Richmond, Virginia, 23235, United States

Location

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

Madison, Wisconsin, 53705, United States

Location

UBC/VCHA Eye Care Centre

Vancouver, British Columbia, V5Z 3N9, Canada

Location

University Health Network - Toronto Western Hospital

Toronto, M5T 2S8, Canada

Location

MeSH Terms

Conditions

Diabetic Retinopathy

Interventions

(R)-2-(3-((benzoxazol-2-yl-d4 (3-(4-methoxyphenoxy-d7)propyl)amino)methyl)phenoxy) butanoic acid

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Results Point of Contact

• Title: Adam Glassman
• Organization: JAEB CENTER FOR HEALTH RESEARCH

drcrnet@jaeb.org

8139758690

Study Officials

• Emily Chew, MD

  National Eye Institute (NEI)

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2017
• First Posted: November 17, 2017
• Study Start: January 15, 2018
• Primary Completion: April 3, 2019
• Study Completion: April 3, 2019
• Last Updated: September 16, 2020
• Results First Posted: September 16, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF

Locations

CA (2); US (69)