PROMINENT-Eye Ancillary Study (Protocol AD)
Condition: Diabetic Retinopathy; Diabetic Macular Edema
MeSH terms: Macular Edema; Retinal Diseases; Diabetic Retinopathy
Intervention: Pemafibrate; Placebo
Intervention description: 0.2 mg orally BID - twice daily; orally BID - twice daily
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: pemafibrate

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.
    

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

          -  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