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PROMINENT-Eye Ancillary Study (Protocol AD)

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ClinicalTrials.gov Identifier: NCT03345901
Recruitment Status : Terminated (recruitment for the substudy did not meet the goals)
First Posted : November 17, 2017
Last Update Posted : April 5, 2019
Sponsor:
Collaborator:
Kowa Company, Ltd.
Information provided by (Responsible Party):
Jaeb Center for Health Research

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 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 : January 15, 2018
Actual Primary Completion Date : April 3, 2019
Actual Study Completion Date : April 3, 2019

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Diabetic retinopathy worsening or diabetic macular edema (DME) development (composite outcome) [ Time Frame: 4 years ]

Secondary Outcome Measures :
  1. Hazard rate of 3-step person-level (for bilateral participants) or 2-step eye-level (for unilateral participants) diabetic retinopathy worsening on the ETDRS Retinopathy Severity Scale or receiving treatment for PDR in at least one study eye at any time [ Time Frame: 4 Years ]
    (irrespective of DME status or treatment)

  2. Hazard rate of developing central-involved DME on OCT with vision loss or receiving treatment for DME in at least one study eye at any time (irrespective of diabetic retinopathy severity level or treatment) [ Time Frame: 4 Years ]
  3. Person-level diabetic retinopathy severity [ Time Frame: 4 Years ]
  4. Percentage of participants with at least a 2-line loss in visual acuity from baseline in at least one study eye [ Time Frame: 4 Years ]
  5. Hazard rate of a composite PDR/DME outcome [ Time Frame: 4 Years ]
    Defined as the time to 2-step diabetic retinopathy worsening on the ETDRS Retinopathy Severity Scale for Individual Eyes (see Table 2 in Section 6) at 2 years or 4 years, development of central-involved DME on OCT with vision loss (as defined above) at 2 years or 4 years, or treatment for DME or PDR at any time

  6. Hazard rate of 2-step diabetic retinopathy worsening or receiving treatment for PDR at any time [ Time Frame: 4 Years ]
    (irrespective of DME status or treatment)

  7. Hazard rate of developing central-involved DME on OCT with vision loss or receiving treatment for DME at any time [ Time Frame: 4 Years ]
    (irrespective of diabetic retinopathy level or treatment)

  8. Eye-level diabetic retinopathy severity [ Time Frame: 4 years ]
  9. Change in OCT central subfield thickness from baseline [ Time Frame: 4 years ]
  10. Change in visual acuity letter score from baseline at 2 years and 4 years [ Time Frame: 4 years ]
  11. Percentage of eyes with at least 2-line loss in visual acuity from baseline [ Time Frame: 4 years ]

Other Outcome Measures:
  1. Changes from randomization in alanine aminotransferase [ Time Frame: 4 Years ]
    Blood test, change measured in units per liter (U/L)

  2. Changes from randomization in aspartate aminotransferase [ Time Frame: 4 Years ]
    Blood test, change from randomization measured in units per liter (U/L)

  3. Changes from randomization in creatine kinase [ Time Frame: 4 Years ]
    Blood test, change from randomization measured in units per liter (U/L) or SI Units (mkat/L)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03345901


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

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Responsible Party: Jaeb Center for Health Research
ClinicalTrials.gov Identifier: NCT03345901     History of Changes
Other Study ID Numbers: DRCR.net Protocol AD
First Posted: November 17, 2017    Key Record Dates
Last Update Posted: April 5, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data related to the eye ancillary study will be made available after completion of the study and publication of the outcome manuscript.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)

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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:
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Macular Edema
Retinal Diseases
Diabetic Retinopathy
Macular Degeneration
Retinal Degeneration
Eye Diseases
Diabetic Angiopathies
Vascular Diseases
Cardiovascular Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases