PROMINENT-Eye Ancillary Study (Protocol AD)

• Sponsor: Jaeb Center for Health Research (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03345901
• Collaborator: Kowa Company, Ltd. (Industry)
• Enrollment: 18
• Locations: 71
• Arms: 2
• Actual Duration (Months): 14.6
• Patients Per Site: 0.3
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Retinopathy; Diabetic Macular Edema	Drug: Pemafibrate; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: PROMINENT-Eye Ancillary Study: Diabetic Retinopathy Outcomes in a Randomized Trial of Pemafibrate Versus Placebo (Protocol AD)
• Actual Study Start Date: Jan 15, 2018
• Actual Primary Completion Date: Apr 3, 2019
• Actual Study Completion Date: Apr 3, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Diabetic Retinopathy Worsening or Diabetic Macular Edema (DME) Development (Composite Outcome) [4 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: 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:

• Study eye exclusion criteria are:

1. 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.

2. 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

3. Aphakia j. Known substantial media opacities that would preclude successful imaging

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Retina and Vitreous Consultants	Phoenix	Arizona	United States	85021
2	Retinal Diagnostic Center	Campbell	California	United States	95008
3	Macula & Retina Institute	Glendale	California	United States	91203
4	Atlantis Eye Care	Huntington Beach	California	United States	92647
5	Loma Linda University Health Care, Department of Ophthalmology	Loma Linda	California	United States	92354
6	South Coast Retina Center	Long Beach	California	United States	90807
7	Northern California Retina Vitreous Associates	Mountain View	California	United States	94040
8	Retinal Consultants of Southern California Medical Group, Inc.	Westlake Village	California	United States	91361
9	National Ophthalmic Research Institute	Fort Myers	Florida	United States	33912
10	University of Florida College of Med., Department of Ophthalmology, Jacksonville Health Science Cent	Jacksonville	Florida	United States	32209
11	Florida Retina Consultants	Lakeland	Florida	United States	33805
12	Retina Macula Specialists of Miami	Miami	Florida	United States	33126
13	Florida Retina Institute	Orlando	Florida	United States	32806
14	Southeast Eye Institute, P.A. dba Eye Associates of Pinellas	Pinellas Park	Florida	United States	33782
15	Sarasota Retina Institute	Sarasota	Florida	United States	34239
16	Emory Eye Center	Atlanta	Georgia	United States	30322-1013
17	Emory Eye Center	Atlanta	Georgia	United States	30322
18	Southeast Retina Center, P.C.	Augusta	Georgia	United States	30909
19	Thomas Eye Group	Sandy Springs	Georgia	United States	30328
20	Northwestern Medical Faculty Foundation	Chicago	Illinois	United States	60611-2987
21	Northwestern Medical Faculty Foundation	Chicago	Illinois	United States	60611
22	University of Illinois at Chicago Medical Center	Chicago	Illinois	United States	60612
23	NorthShore University HealthSystem	Glenview	Illinois	United States	60026
24	Illinois Retina Associates, S.C.	Oak Park	Illinois	United States	60304
25	John-Kenyon American Eye Institute	New Albany	Indiana	United States	47150
26	Wolfe Eye Clinic	West Des Moines	Iowa	United States	50266
27	Mid-America Retina Consultants, P.A.	Overland Park	Kansas	United States	66211
28	Retina Associates, P.A.	Shawnee Mission	Kansas	United States	66204
29	Retina and Vitreous Associates of Kentucky	Lexington	Kentucky	United States	40509
30	Eye Associates of Northeast Louisiana dba Haik Humble Eye Center	West Monroe	Louisiana	United States	71291-4452
31	Eye Associates of Northeast Louisiana dba Haik Humble Eye Center	West Monroe	Louisiana	United States	71291
32	Elman Retina Group, P.A.	Baltimore	Maryland	United States	21237
33	Wilmer Eye Institute at Johns Hopkins	Baltimore	Maryland	United States	21287
34	Valley Eye Physicians and Surgeons	Ayer	Massachusetts	United States	01432
35	Ophthalmic Consultants of Boston	Boston	Massachusetts	United States	02114
36	Joslin Diabetes Center	Boston	Massachusetts	United States	02215
37	Kellogg Eye Center, University of Michigan	Ann Arbor	Michigan	United States	48105
38	Henry Ford Health System, Dept of Ophthalmology and Eye Care Services	Detroit	Michigan	United States	48202-2689
39	Henry Ford Health System, Dept of Ophthalmology and Eye Care Services	Detroit	Michigan	United States	48202
40	Vitreo-Retinal Associates	Grand Rapids	Michigan	United States	49546
41	Retina Center, PA	Minneapolis	Minnesota	United States	34239
42	Retina Center, PA	Minneapolis	Minnesota	United States	55404
43	The Retina Institute	Saint Louis	Missouri	United States	63128
44	Eye Associates of New Mexico	Albuquerque	New Mexico	United States	87109-5857
45	Eye Associates of New Mexico	Albuquerque	New Mexico	United States	87109
46	MaculaCare	New York	New York	United States	10021
47	Retina Associates of Western New York	Rochester	New York	United States	14620
48	Retina-Vitreous Surgeons of Central New York, PC	Syracuse	New York	United States	13224
49	Western Carolina Clinical Research, LLC	Asheville	North Carolina	United States	28803
50	Kittner Eye Center	Chapel Hill	North Carolina	United States	27517-8923
51	Kittner Eye Center	Chapel Hill	North Carolina	United States	27517
52	Charlotte Eye, Ear, Nose and Throat Assoc., PA	Charlotte	North Carolina	United States	28210
53	Retina Vitreous Center	Edmond	Oklahoma	United States	73103
54	Dean A. McGee Eye Institute	Oklahoma City	Oklahoma	United States	73104
55	Retina Vitreous Consultants	Monroeville	Pennsylvania	United States	15146
56	Southeastern Retina Associates	Chattanooga	Tennessee	United States	37421
57	Southeastern Retina Associates, P.C.	Knoxville	Tennessee	United States	37909
58	Retina Research Center	Austin	Texas	United States	78705
59	Robert E. Torti, MD, PA dba Retina Specialists	DeSoto	Texas	United States	75115-2011
60	Valley Retina Institute	DeSoto	Texas	United States	75115
61	Retina Center of Texas	Grapevine	Texas	United States	76051
62	Baylor Eye Physicians and Surgeons	Houston	Texas	United States	77030-4101
63	Baylor Eye Physicians and Surgeons	Houston	Texas	United States	77030
64	Retina Consultants of Houston, PA	Houston	Texas	United States	77030
65	Valley Retina Institute	McAllen	Texas	United States	78503
66	Medical Center Ophthalmology Associates	San Antonio	Texas	United States	78240
67	Retinal Consultants of San Antonio	San Antonio	Texas	United States	78240
68	Retina Institute of Virginia	Richmond	Virginia	United States	23235
69	University of Wisconsin-Madison, Dept of Ophthalmology/Retina Service	Madison	Wisconsin	United States	53705
70	UBC/VCHA Eye Care Centre	Vancouver	British Columbia	Canada	V5Z 3N9
71	University Health Network - Toronto Western Hospital	Toronto		Canada	M5T 2S8

Sponsors and Collaborators

• Jaeb Center for Health Research
• Kowa Company, Ltd.

Investigators

• Study Chair: Emily Chew, MD, National Eye Institute (NEI)

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 14, 2018

More Information

Publications

None provided.

• Responsible Party: Jaeb Center for Health Research
• ClinicalTrials.gov Identifier: NCT03345901
• Other Study ID Numbers: DRCR.net Protocol AD
• First Posted: Nov 17, 2017
• Last Update Posted: Sep 16, 2020
• Last Verified: Aug 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Jaeb Center for Health Research: pemafibrate
• Additional relevant MeSH terms: Macular Edema; Retinal Diseases; Diabetic Retinopathy

Study Results

Participant Flow

Arm/Group Title	Enrolled Participants
Arm/Group Description	The study was terminated before participants were randomized to an arm. Data include all enrolled participants.
Period Title: Overall Study
STARTED	18
COMPLETED	0
NOT COMPLETED	18

Baseline Characteristics

Arm/Group Title	Enrolled Participants
Arm/Group Description	The study was terminated before participants were randomized to an arm. Data include all enrolled participants.
Overall Participants	18
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	65
Sex: Female, Male (Count of Participants)
Female	5 27.8%
Male	13 72.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 5.6%
Not Hispanic or Latino	17 94.4%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 16.7%
White	15 83.3%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The study was terminated before the participants were randomized or any study visit occurred.

Arm/Group Title	Enrolled Participants
Arm/Group Description	The study was terminated before participants were randomized to an arm. Data include all enrolled participants.
Measure Participants	0

Adverse Events

Time Frame	No adverse event data were collected
Adverse Event Reporting Description	The study was terminated and no adverse event data were collected.
Arm/Group Title	Pemafibrate		Placebo
Arm/Group Description	.2 mg pemafibrate orally BID Pemafibrate: 0.2 mg orally BID - twice daily		Placebo pill orally BID Placebo: orally BID - twice daily
All Cause Mortality
	Pemafibrate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Serious Adverse Events
	Pemafibrate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Pemafibrate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.