CClinicalTrials.gg
TerminatedNCT03345901Updated Sep 16, 2020Results posted

PROMINENT-Eye Ancillary Study (Protocol AD)

A Phase 3 interventional study of Pemafibrate and Placebo in Diabetic Retinopathy and Diabetic Macular Edema, sponsored by Jaeb Center for Health Research. Terminated at 71 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-09-16.

Sponsored by Jaeb Center for Health Research · Phase 3, Interventional, and Prevention

Why this study was terminated
recruitment for the substudy did not meet the goals
Phase
Phase 3
Study type
Interventional
Enrollment
18
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

02

Conditions studied

  • Diabetic Retinopathy
  • Diabetic Macular Edema

Keywords

  • pemafibrate
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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

04

Study design

Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
18 participants (actual)

Study arms

  • Experimental
    Pemafibrate

    .2 mg pemafibrate orally BID

    Drug: Pemafibrate

  • Placebo comparator
    Placebo

    Placebo pill orally BID

    Drug: Placebo

Interventions

  • DrugPemafibrate

    0.2 mg orally BID - twice daily

  • DrugPlacebo

    orally BID - twice daily

05

What researchers measure

Primary outcomes

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

    Time frame: 4 years

06

Results

Posted Sep 16, 2020

Participant flow

Participant flow — Overall Study
MilestoneEnrolled Participants
Started18
Completed0
Not completed18
Withdrew: The study was terminated18

Outcome measures

PrimaryDiabetic Retinopathy Worsening or Diabetic Macular Edema (DME) Development (Composite Outcome)
Time frame:
4 years

No measurements were reported for this outcome.

Adverse events

Collected over No adverse event data were collected. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Pemafibrate———
Placebo———

Baseline characteristics

All enrolled participants

Age, Continuous
Age, Continuous(years)Enrolled Participants
Mean65 (54 to 74)
Sex: Female, Male
Sex: Female, Male(Participants)Enrolled Participants
Female5
Male13
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Enrolled Participants
Hispanic or Latino1
Not Hispanic or Latino17
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Enrolled Participants
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American3
White15
More than one race0
Unknown or Not Reported0
07

Study locations

71 sites
  • Arizona Retina and Vitreous Consultants
    Phoenix, Arizona 85021, United States
  • Retinal Diagnostic Center
    Campbell, California 95008, United States
  • Macula & Retina Institute
    Glendale, California 91203, United States
  • Atlantis Eye Care
    Huntington Beach, California 92647, United States
  • Loma Linda University Health Care, Department of Ophthalmology
    Loma Linda, California 92354, United States
  • South Coast Retina Center
    Long Beach, California 90807, United States
  • Northern California Retina Vitreous Associates
    Mountain View, California 94040, United States
  • Retinal Consultants of Southern California Medical Group, Inc.
    Westlake Village, California 91361, United States
  • National Ophthalmic Research Institute
    Fort Myers, Florida 33912, United States
  • University of Florida College of Med., Department of Ophthalmology, Jacksonville Health Science Cent
    Jacksonville, Florida 32209, United States
  • Florida Retina Consultants
    Lakeland, Florida 33805, United States
  • Retina Macula Specialists of Miami
    Miami, Florida 33126, United States
  • Florida Retina Institute
    Orlando, Florida 32806, United States
  • Southeast Eye Institute, P.A. dba Eye Associates of Pinellas
    Pinellas Park, Florida 33782, United States
  • Sarasota Retina Institute
    Sarasota, Florida 34239, United States
  • Emory Eye Center
    Atlanta, Georgia 30322-1013, United States
  • Emory Eye Center
    Atlanta, Georgia 30322, United States
  • Southeast Retina Center, P.C.
    Augusta, Georgia 30909, United States
  • Thomas Eye Group
    Sandy Springs, Georgia 30328, United States
  • Northwestern Medical Faculty Foundation
    Chicago, Illinois 60611-2987, United States
  • Northwestern Medical Faculty Foundation
    Chicago, Illinois 60611, United States
  • University of Illinois at Chicago Medical Center
    Chicago, Illinois 60612, United States
  • NorthShore University HealthSystem
    Glenview, Illinois 60026, United States
  • Illinois Retina Associates, S.C.
    Oak Park, Illinois 60304, United States
  • John-Kenyon American Eye Institute
    New Albany, Indiana 47150, United States
  • Wolfe Eye Clinic
    West Des Moines, Iowa 50266, United States
  • Mid-America Retina Consultants, P.A.
    Overland Park, Kansas 66211, United States
  • Retina Associates, P.A.
    Shawnee Mission, Kansas 66204, United States
  • Retina and Vitreous Associates of Kentucky
    Lexington, Kentucky 40509, United States
  • Eye Associates of Northeast Louisiana dba Haik Humble Eye Center
    West Monroe, Louisiana 71291-4452, United States
  • Eye Associates of Northeast Louisiana dba Haik Humble Eye Center
    West Monroe, Louisiana 71291, United States
  • Elman Retina Group, P.A.
    Baltimore, Maryland 21237, United States
  • Wilmer Eye Institute at Johns Hopkins
    Baltimore, Maryland 21287, United States
  • Valley Eye Physicians and Surgeons
    Ayer, Massachusetts 01432, United States
  • Ophthalmic Consultants of Boston
    Boston, Massachusetts 02114, United States
  • Joslin Diabetes Center
    Boston, Massachusetts 02215, United States
  • Kellogg Eye Center, University of Michigan
    Ann Arbor, Michigan 48105, United States
  • Henry Ford Health System, Dept of Ophthalmology and Eye Care Services
    Detroit, Michigan 48202-2689, United States
  • Henry Ford Health System, Dept of Ophthalmology and Eye Care Services
    Detroit, Michigan 48202, United States
  • Vitreo-Retinal Associates
    Grand Rapids, Michigan 49546, United States
  • Retina Center, PA
    Minneapolis, Minnesota 34239, United States
  • Retina Center, PA
    Minneapolis, Minnesota 55404, United States
  • The Retina Institute
    Saint Louis, Missouri 63128, United States
  • Eye Associates of New Mexico
    Albuquerque, New Mexico 87109-5857, United States
  • Eye Associates of New Mexico
    Albuquerque, New Mexico 87109, United States
  • MaculaCare
    New York, New York 10021, United States
  • Retina Associates of Western New York
    Rochester, New York 14620, United States
  • Retina-Vitreous Surgeons of Central New York, PC
    Syracuse, New York 13224, United States
  • Western Carolina Clinical Research, LLC
    Asheville, North Carolina 28803, United States
  • Kittner Eye Center
    Chapel Hill, North Carolina 27517-8923, United States
  • Kittner Eye Center
    Chapel Hill, North Carolina 27517, United States
  • Charlotte Eye, Ear, Nose and Throat Assoc., PA
    Charlotte, North Carolina 28210, United States
  • Retina Vitreous Center
    Edmond, Oklahoma 73103, United States
  • Dean A. McGee Eye Institute
    Oklahoma City, Oklahoma 73104, United States
  • Retina Vitreous Consultants
    Monroeville, Pennsylvania 15146, United States
  • Southeastern Retina Associates
    Chattanooga, Tennessee 37421, United States
  • Southeastern Retina Associates, P.C.
    Knoxville, Tennessee 37909, United States
  • Retina Research Center
    Austin, Texas 78705, United States
  • Robert E. Torti, MD, PA dba Retina Specialists
    DeSoto, Texas 75115-2011, United States
  • Valley Retina Institute
    DeSoto, Texas 75115, United States
  • Retina Center of Texas
    Grapevine, Texas 76051, United States
  • Baylor Eye Physicians and Surgeons
    Houston, Texas 77030-4101, United States
  • Baylor Eye Physicians and Surgeons
    Houston, Texas 77030, United States
  • Retina Consultants of Houston, PA
    Houston, Texas 77030, United States
  • Valley Retina Institute
    McAllen, Texas 78503, United States
  • Medical Center Ophthalmology Associates
    San Antonio, Texas 78240, United States
  • Retinal Consultants of San Antonio
    San Antonio, Texas 78240, United States
  • Retina Institute of Virginia
    Richmond, Virginia 23235, United States
  • University of Wisconsin-Madison, Dept of Ophthalmology/Retina Service
    Madison, Wisconsin 53705, United States
  • UBC/VCHA Eye Care Centre
    Vancouver, British Columbia V5Z 3N9, Canada
  • University Health Network - Toronto Western Hospital
    Toronto, M5T 2S8, Canada
08

References and documents

Study documents

  • Protocol and statistical analysis plan · Mar 14, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Data related to the eye ancillary study will be made available after completion of the study and publication of the outcome manuscript.

Supporting information: Study protocol, Sap, Icf

09

Registry details

Key details

Study ID
NCT03345901
Lead sponsor
Jaeb Center for Health Research
Collaborators
Kowa Company, Ltd.
Responsible party
Sponsor
First posted
Nov 17, 2017
Start date
Jan 15, 2018
Primary completion
Apr 3, 2019
Completion
Apr 3, 2019
Results posted
Sep 16, 2020
Last update
Sep 16, 2020

Study contacts

Emily Chew, MD
study chair · National Eye Institute (NEI)

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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