Diabetic Retinopathy, Macular Edema
Conditions
Keywords
Diabetic Macular Edema (DME)
Brief summary
Researchers are looking for new ways to treat diabetic macular edema (DME). In this trial, researchers want to learn if a trial medicine called MK-8748 can treat DME. An available standard (usual) treatment for DME is aflibercept. However, standard treatments such as aflibercept may not work for every person. The main goal of this trial is to learn if MK-8748 works as well as aflibercept to treat DME.
Interventions
DRUGMK-8748
Administered by intravitreal injection (IVT)
DRUGAflibercept
Administered by intravitreal injection (IVT)
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The main inclusion criteria include but are not limited to the following: * Has Type 1 or Type 2 diabetes mellitus and a hemoglobin A1c (HbA1c) of ≤12% * Has a decrease in vision in the study eye determined by the Investigator to be primarily the result of diabetic macular edema (DME) * For participants who are treatment-naïve for DME, the diagnosis must have been made within 9 months of screening. For all treatment-experienced participants, the first treatment should have been no longer than 3 years prior to the Screening visit
Exclusion criteria
The main
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Best-Corrected Visual Acuity (BCVA) (Early Treatment of Diabetic Retinopathy Study [ETDRS] Letters) From Baseline to Year 1 | Baseline and 1 Year | Participants' BCVA in the study eye will be measured using the Early Treatment of Diabetic Retinopathy (ETDRS) methodology. The ETDRS letter score ranges from 0 to 100, with a higher score indicating better visual acuity. Mean change in ETDRS letters from baseline to Year 1 will be assessed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Central Subfield Thickness (CST) from Baseline to Week 52 | Baseline and Week 52 | Central subfield thickness (CST) in the study eye will be measured in microns using optical coherence tomography (OCT). The mean change in CST from baseline to Year 1 will be presented. |
| Mean Change in CST from Baseline Over Time | Up to approximately 2 years | Central subfield thickness (CST) in the study eye will be measured in microns using optical coherence tomography (OCT). The mean change in CST from baseline over time will be presented. |
| Time to Absence of Diabetic Macular Edema (DME) at Week 52 | Up to approximately Week 52 | The absence of Diabetic Macular Edema (DME) is defined as a Central Subfield Thickness (CST) of \<300 μm measured using optical coherence tomography (OCT). The time to absence of Diabetic Macular Edema (DME) in the study eye up to Week 52 will be presented. |
| Proportion of Participants with Absence of Intraretinal Fluid Over Time | Up to approximately 2 years | Participants' intraretinal fluid in the study eye will be measured using optical coherence tomography (OCT). The proportion of participants with absence of intraretinal fluid over time will be presented. |
| Proportion of Participants with Absence of Subretinal Fluid Over Time | Up to approximately 2 years | Participants' subretinal fluid in the study eye will be measured using optical coherence tomography (OCT). The proportion of participants with absence of subretinal fluid over time will be presented. |
| Proportion of Participants with Absence of Intraretinal Fluid and Subretinal Fluid Over Time | Up to approximately 2 years | Participants' subretinal fluid and intraretinal fluid in the study eye will be measured using optical coherence tomography (OCT). The proportion of participants with absence of intraretinal and subretinal fluid over time will be presented. |
| Proportion of Participants with Diabetic Retinopathy Severity Scale (DRSS) Score Improvement of ≥2 Steps from Baseline to Year 1 | Baseline and 1 Year | The Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy (DR) into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy (PDR). DRSS grades= 10 (DR absent) - 85 (very advanced PDR), DRSS 90 = ungradable. All DRSS values are converted into a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR), allowing derivation of ≥2-step change from baseline for post-baseline assessment. A lower score represents less advanced diabetic retinopathy. The proportion of participants with ≥2 step improvement in DRSS score from baseline to year 1 will be presented. |
| Proportion of Participants with DRSS Score Improvement of ≥3 Steps from Baseline to Year 1 | Baseline and 1 Year | The Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy (DR) into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy (PDR). DRSS grades= 10 (DR absent) - 85 (very advanced PDR), DRSS 90 = ungradable. All DRSS values are converted into a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR), allowing derivation of ≥2-step change from baseline for post-baseline assessment. A lower score represents less advanced diabetic retinopathy. The proportion of participants with ≥3 step improvement in DRSS score from baseline to year 1 will be presented. |
| Proportion of Participants with Resolution of Macular Leakage on Fluorescein Angiography (FA) at Week 24 | Up to approximately Week 24 | Fluorescein Angiography (FA) images will be used to determine the resolution of macular leakage in the study eye, defined as 0 to 1 mm\^2. The proportion of participants with resolution of macular leakage at Week 24 will be presented. |
| Mean change in Optical Coherence Tomography (OCT) Central Subfield Thickness (CST) from Baseline to Week 104 | Baseline and Week 104 | Central subfield thickness (CST) in the study eye will be measured in microns using optical coherence tomography (OCT). The mean change in OCT CST from baseline to Week 104 will be presented. |
| Proportion of Participants with DRSS Score Improvement of ≥2 Steps from Baseline to Week 104 | Baseline and Week 104 | The Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy (DR) into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy (PDR). DRSS grades= 10 (DR absent) - 85 (very advanced PDR), DRSS 90 = ungradable. All DRSS values are converted into a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR), allowing derivation of ≥2-step change from baseline for post-baseline assessment. A lower score represents less advanced diabetic retinopathy. The proportion of participants with ≥2 step improvement in DRSS score from baseline to week 104 will be presented. |
| Proportion of Participants with DRSS Score Improvement of ≥3 Steps from Baseline to Week 104 | Baseline and Week 104 | The Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy (DR) into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy (PDR). DRSS grades= 10 (DR absent) - 85 (very advanced PDR), DRSS 90 = ungradable. All DRSS values are converted into a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR), allowing derivation of ≥2-step change from baseline for post-baseline assessment. A lower score represents less advanced diabetic retinopathy. The proportion of participants with ≥3 step improvement in DRSS score from baseline to week 104 will be presented. |
| Proportion of Participants Without Retinal Fluid at the Foveal Center on OCT at Week 104 | Up to approximately Week 104 | Optical coherence tomography (OCT) will be used to measure retinal fluid at the foveal center of the study eye. The proportion of participants without retinal fluid at the foveal center on OCT at Week 104 will be presented. |
| Mean change in Foveal Avascular Zone (FAZ) Area on Fluorescein Angiography (FA) from Baseline to Year 1 | Baseline and 1 Year | Fluorescein Angiography (FA) images will be used to measure the Foveal Avascular Zone (FAZ) area of the study eye. The mean change in FAZ area on FA from baseline to year 1 will be presented. |
| Proportion of Participants with Reduction in FAZ Area on FA from Baseline to Year 1 | Baseline and 1 Year | Fluorescein Angiography (FA) images will be used to measure the Foveal Avascular Zone (FAZ) area of the study eye. The proportion of participants with reduction of FAZ area on FA from baseline to year 1 will be presented. |
| Proportion of Participants Without Retinal Fluid at the Foveal Center at Week 52 | Up to approximately Week 52 | Participants' retinal fluid in the study eye will be measured using optical coherence tomography (OCT). The proportion of participants without retinal fluid at the foveal center at week 52 will be presented. |
| Mean Number of Intravitreal (IVT) Injections from Week 56 to Week 104 | Up to approximately 48 Weeks | The mean number of intravitreal (IVT) Injections from week 56 to week 104 will be presented. |
| Proportion of Participants on a Personalized Treatment Interval (PTI) of every 8 weeks (Q8W) at Week 104 | Up to approximately Week 104 | The proportion of participants on a personalized treatment interval (PTI) of every 8 weeks (Q8W) at Week 104 will be presented. |
| Proportion of Participants on a Personalized Treatment Interval (PTI) of every 12 weeks (Q12W) at Week 104 | Up to approximately Week 104 | The proportion of participants on a personalized treatment interval (PTI) of every 12 weeks (Q12W) at Week 104 will be presented. |
| Proportion of Participants on a Personalized Treatment Interval (PTI) of every 16 weeks (Q16W) at Week 104 | Up to approximately Week 104 | The proportion of participants on a personalized treatment interval (PTI) of every 16 weeks (Q16W) at Week 104 will be presented. |
| Proportion of Participants who Gain ≥5 ETDRS Letters from Baseline to Year 1 | Baseline and 1 Year | Participants' BCVA in the study eye will be measured using the Early Treatment of Diabetic Retinopathy (ETDRS) methodology. The ETDRS letter score ranges from 0 to 100, with a higher score indicating better visual acuity. The proportion of participants who gain ≥5 ETDRS letters from baseline to year 1 will be presented. |
| Proportion of Participants who Gain ≥10 ETDRS Letters from Baseline to Year 1 | Baseline and 1 Year | Participants' BCVA in the study eye will be measured using the Early Treatment of Diabetic Retinopathy (ETDRS) methodology. The ETDRS letter score ranges from 0 to 100, with a higher score indicating better visual acuity. The proportion of participants who gain ≥10 ETDRS letters from baseline to year 1 will be presented. |
| Proportion of Participants who Gain ≥15 ETDRS Letters from Baseline to Year 1 | Baseline and 1 Year | Participants' BCVA in the study eye will be measured using the Early Treatment of Diabetic Retinopathy (ETDRS) methodology. The ETDRS letter score ranges from 0 to 100, with a higher score indicating better visual acuity. The proportion of participants who gain ≥15 ETDRS letters from baseline to year 1 will be presented. |
| Proportion of Participants who Lose ≥5 ETDRS Letters from Baseline to Year 1 | Baseline and 1 Year | Participants' BCVA in the study eye will be measured using the Early Treatment of Diabetic Retinopathy (ETDRS) methodology. The ETDRS letter score ranges from 0 to 100, with a higher score indicating better visual acuity. The proportion of participants who lose ≥5 ETDRS letters from baseline to year 1 will be presented. |
| Proportion of Participants who Lose ≥10 ETDRS Letters from Baseline to Year 1 | Baseline and 1 Year | Participants' BCVA in the study eye will be measured using the Early Treatment of Diabetic Retinopathy (ETDRS) methodology. The ETDRS letter score ranges from 0 to 100, with a higher score indicating better visual acuity. The proportion of participants who lose ≥10 ETDRS letters from baseline to year 1 will be presented. |
| Proportion of participants who Lose ≥15 ETDRS Letters from Baseline to Year 1 | Baseline and 1 Year | Participants' BCVA in the study eye will be measured using the Early Treatment of Diabetic Retinopathy (ETDRS) methodology. The ETDRS letter score ranges from 0 to 100, with a higher score indicating better visual acuity. The proportion of participants who lose ≥15 ETDRS letters from baseline to year 1 will be presented. |
| Time to gain ≥5 ETDRS Letters Over Time | Up to approximately 2 years | Participants' BCVA in the study eye will be measured using the Early Treatment of Diabetic Retinopathy (ETDRS) methodology. The ETDRS letter score ranges from 0 to 100, with a higher score indicating better visual acuity. The time to gain ≥5 ETDRS letters over time will be presented. |
| Time to gain ≥10 ETDRS Letters at Week 52 | Up to approximately Week 52 | Participants' BCVA in the study eye will be measured using the Early Treatment of Diabetic Retinopathy (ETDRS) methodology. The ETDRS letter score ranges from 0 to 100, with a higher score indicating better visual acuity. The time to gain ≥10 ETDRS letters up to Week 52 will be presented. |
| Time to gain ≥15 ETDRS letters at Week 52 | Up to approximately Week 52 | Participants' BCVA in the study eye will be measured using the Early Treatment of Diabetic Retinopathy (ETDRS) methodology. The ETDRS letter score ranges from 0 to 100, with a higher score indicating better visual acuity. The time to gain ≥15 ETDRS letters up to Week 52 will be presented. |
| Mean Change in BCVA (ETDRS letters) from Baseline Over Time | Baseline and 2 Years | Participants' BCVA in the study eye will be measured using the Early Treatment of Diabetic Retinopathy (ETDRS) methodology. The ETDRS letter score ranges from 0 to 100, with a higher score indicating better visual acuity. The mean change in BCVA (ETDRS) letters from baseline over time will be presented. |
| Proportion of Participants with BCVA Snellen Equivalent of 20/20 or Better at Year 1 | Up to approximately 1 year | Participants' BCVA in the study eye will be measured using the Early Treatment of Diabetic Retinopathy (ETDRS) methodology. The ETDRS letter score ranges from 0 to 100, with a higher score indicating better visual acuity. The number of letters read correctly, Snellen fraction are converted to a decimal scale. There are 11 lines on a standard Snellen chart ranging from 0.1 (20/200) at worst to 2.0 (20/10) at best. 20/20 on the decimal scale is equal to 1.0. The higher the number of letters read correctly (higher number on the decimal scale), the better the vision (or visual acuity). The Snellen equivalent of 20/20 or better is defined as ≥84 letters correctly read in the ETDRS chart. The proportion of participants with BCVA Snellen equivalent of 20/20 or better at year 1 will be presented. |
| Proportion of Participants with BCVA Snellen equivalent of 20/200 or Worse at Year 1 | Up to approximately 1 year | Participants' BCVA in the study eye will be measured using the Early Treatment of Diabetic Retinopathy (ETDRS) methodology. The ETDRS letter score ranges from 0 to 100, with a higher score indicating better visual acuity. The number of letters read correctly, Snellen fraction are converted to a decimal scale. There are 11 lines on a standard Snellen chart ranging from 0.1 (20/200) at worst to 2.0 (20/10) at best. 20/20 on the decimal scale is equal to 1.0. The higher the number of letters read correctly (higher number on the decimal scale), the better the vision (or visual acuity). The Snellen equivalent of 20/200 or worse is defined as ≤38 letters correctly read in the ETDRS chart. The proportion of participants with BCVA Snellen equivalent of 20/200 or Worse at year 1 will be presented. |
| Proportion of Participants with BCVA Snellen Equivalent of 20/40 or Better at Year 1 | Up to approximately 1 year | Participants' BCVA in the study eye will be measured using the Early Treatment of Diabetic Retinopathy (ETDRS) methodology. The ETDRS letter score ranges from 0 to 100, with a higher score indicating better visual acuity. The number of letters read correctly, Snellen fraction are converted to a decimal scale. There are 11 lines on a standard Snellen chart ranging from 0.1 (20/200) at worst to 2.0 (20/10) at best. 20/20 on the decimal scale is equal to 1.0. The higher the number of letters read correctly (higher number on the decimal scale), the better the vision (or visual acuity). The Snellen equivalent of 20/40 or better is defined as ≥69 letters correctly read in the ETDRS chart. The proportion of participants with BCVA Snellen equivalent of 20/40 or better at year 1 will be presented. |
| Mean Change in BCVA from Baseline to Year 2 | Baseline and Year 2 | Participants' BCVA in the study eye will be measured using the Early Treatment of Diabetic Retinopathy (ETDRS) methodology. The ETDRS letter score ranges from 0 to 100, with a higher score indicating better visual acuity. Mean change in ETDRS letters from baseline to year 2 will be assessed. |
| Proportion of Participants with BCVA Snellen Equivalent of 20/40 or Better at Year 2 | Up to approximately 2 years | Participants' BCVA in the study eye will be measured using the Early Treatment of Diabetic Retinopathy (ETDRS) methodology. The ETDRS letter score ranges from 0 to 100, with a higher score indicating better visual acuity. The number of letters read correctly, Snellen fraction are converted to a decimal scale. There are 11 lines on a standard Snellen chart ranging from 0.1 (20/200) at worst to 2.0 (20/10) at best. 20/20 on the decimal scale is equal to 1.0. The higher the number of letters read correctly (higher number on the decimal scale), the better the vision (or visual acuity). The Snellen equivalent of 20/40 or better is defined as ≥69 letters correctly read in the ETDRS chart. The proportion of participants with BCVA Snellen equivalent of 20/40 or better at year 2 will be presented. |
| Proportion of Participants with BCVA Snellen Equivalent of 20/200 or Worse at Year 2 | Up to approximately 2 years | Participants' BCVA in the study eye will be measured using the Early Treatment of Diabetic Retinopathy (ETDRS) methodology. The ETDRS letter score ranges from 0 to 100, with a higher score indicating better visual acuity. The number of letters read correctly, Snellen fraction are converted to a decimal scale. There are 11 lines on a standard Snellen chart ranging from 0.1 (20/200) at worst to 2.0 (20/10) at best. 20/20 on the decimal scale is equal to 1.0. The higher the number of letters read correctly (higher number on the decimal scale), the better the vision (or visual acuity). The Snellen equivalent of 20/200 or worse is defined as ≤38 letters correctly read in the ETDRS chart. The proportion of participants with BCVA Snellen equivalent of 20/200 or Worse at year 2 will be presented. |
| Proportion of Participants who Gain ≥5 ETDRS Letters from Baseline to Year 2 | Baseline and 2 Years | Participants' BCVA in the study eye will be measured using the Early Treatment of Diabetic Retinopathy (ETDRS) methodology. The ETDRS letter score ranges from 0 to 100, with a higher score indicating better visual acuity. The proportion of participants who gain ≥5 ETDRS Letters from baseline to year 2 will be presented. |
| Proportion of Participants who Gain ≥10 ETDRS Letters from Baseline to Year 2 | Baseline and 2 Years | Participants' BCVA in the study eye will be measured using the Early Treatment of Diabetic Retinopathy (ETDRS) methodology. The ETDRS letter score ranges from 0 to 100, with a higher score indicating better visual acuity. The proportion of participants who gain ≥10 ETDRS Letters from baseline to year 2 will be presented. |
| Proportion of Participants who Gain ≥15 ETDRS Letters from Baseline to Year 2 | Baseline and 2 Years | Participants' BCVA in the study eye will be measured using the Early Treatment of Diabetic Retinopathy (ETDRS) methodology. The ETDRS letter score ranges from 0 to 100, with a higher score indicating better visual acuity. The proportion of participants who gain ≥15 ETDRS letters from baseline to year 2 will be presented. |
| Proportion of Participants who Lose ≥5 ETDRS Letters from Baseline to Year 2 | Baseline to 2 Years | Participants' BCVA in the study eye will be measured using the Early Treatment of Diabetic Retinopathy (ETDRS) methodology. The ETDRS letter score ranges from 0 to 100, with a higher score indicating better visual acuity. The proportion of participants who lose ≥5 ETDRS Letters baseline to year 2 will be presented. |
| Proportion of Participants who Lose ≥10 ETDRS Letters from Baseline to Year 2 | Baseline to 2 Years | Participants' BCVA in the study eye will be measured using the Early Treatment of Diabetic Retinopathy (ETDRS) methodology. The ETDRS letter score ranges from 0 to 100, with a higher score indicating better visual acuity. The proportion of participants who lose ≥10 ETDRS letters from baseline to year 2 will be presented. |
| Proportion of Participants who Lose ≥15 ETDRS Letters from Baseline to Year 2 | Baseline and 2 years | Participants' BCVA in the study eye will be measured using the Early Treatment of Diabetic Retinopathy (ETDRS) methodology. The ETDRS letter score ranges from 0 to 100, with a higher score indicating better visual acuity. The proportion of participants who lose ≥15 ETDRS Letters from baseline to year 2 will be presented. |
| Change from Baseline in National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) Version Composite Score at Week 48 | Baseline and Week 48 | The NEI-VFQ-25 is a validated and reliable 25-item survey that measures the influence of visual disability and visual symptoms on generic health domains (emotional well-being, social functioning and task-oriented domains). The composite score ranges from 0-100 with the higher score indicating better visual function. The change from baseline in NEI-VFQ-25 version composite score at week 48 will be presented. |
| Change from Baseline in National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) Version Composite Score at Week 104 | Baseline and Week 104 | The NEI-VFQ-25 is a validated and reliable 25-item survey that measures the influence of visual disability and visual symptoms on generic health domains (emotional well-being, social functioning and task-oriented domains). The composite score ranges from 0-100 with the higher score indicating better visual function. The change from baseline in NEI-VFQ-25 version composite score at week 104 will be presented. |
| Number of Participants who Experience a Systemic Adverse Events (AEs) | Up to approximately 2 years | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience a systemic AE will be presented. |
| Number of Participants who Experience an Ocular Adverse Events (AEs) | Up to approximately 2 years | An ocular adverse event (OAE) is defined as any untoward medical occurrence involving the eye or ocular adnexa (including eyelids, conjunctiva, lacrimal apparatus, extraocular muscles, and orbit) that: Occurs or worsens after the first administration of the investigational product (IP) or a study-related ocular procedure, and does not necessarily have a causal relationship with the IP or procedure. OAEs include, but are not limited to, changes in: Symptoms (e.g., ocular pain, photophobia, floaters, blurred vision), Visual function (e.g., best-corrected visual acuity \[BCVA\], visual field). Intraocular pressure (IOP), Anterior segment findings (e.g., conjunctival hyperemia, keratitis, anterior chamber inflammation), Posterior segment findings (e.g., vitreous inflammation, retinal hemorrhages, retinal tears or detachment, macular edema), or ocular adnexa (e.g., eyelid edema, ptosis). The number of participants who experience an ocular AE will be presented. |
| Number of Participants who Discontinue Study Treatment Due to an AE | Up to approximately 2 years | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study treatment due to an AE will be reported. |
| Number of Participants with Antidrug Antibodies (ADA) to MK-8748 | At designated time points (up to approximately 104 weeks) | Blood samples collected at designated timepoints will be used to determine the ADA response to MK-8748. The number of participants with ADA to MK-8748 will be presented. |
| Maximum Plasma Concentration (Cmax) of MK-8748 | At designated time points (up to approximately 104 weeks) | Cmax is defined as the peak concentration over the dosing interval. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Cmax of MK-8748. |
| Plasma Trough Concentration (Ctrough) of MK-8748 | At designated time points (up to approximately 104 weeks) | Ctrough is defined as the trough concentration. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Ctrough of MK-8748. |
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed