A Clinical Trial of MK-8748 Compared to Aflibercept in Participants With Diabetic Macular Edema (MK-8748-005)

Phase 3Not Yet RecruitingNCT07705607

Merck Sharp & Dohme LLC1,104 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

1,104

Conditions

Diabetic Retinopathy Macular Edema

Interventions

MK-8748DRUG

Administered by intravitreal injection (IVT)

AfliberceptDRUG

Administered by intravitreal injection (IVT)

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 exclusion criteria include but are not limited to the following: * Has had renal failure requiring renal transplant, hemodialysis, or peritoneal dialysis or has renal failure anticipated to require hemodialysis or peritoneal dialysis at any time during the study * Has history of stroke (cerebral vascular accident) or myocardial infarction within 180 days to first dose of study intervention * Has newly diagnosed or previously untreated diabetes mellitus and initiated oral or injectable anti-diabetic medication within 3 months to first dose of study intervention * Has history of cataract surgery and/or minimally invasive glaucoma surgery in the study eye within 90 days of screening * Has any treatment for complications of cataract surgery with steroids or yttrium aluminum garnet (YAG) laser capsulotomy in the study eye within 90 days of screening * Has advanced or uncontrolled glaucoma in the study eye * Has any history of retinal detachment or treatment or surgery for retinal detachment in the study eye * Has active retinal disease other than the condition under investigation in the study eye * Has uncontrolled blood pressure at screening

Outcomes

Primary Outcomes

Mean Change in Best-Corrected Visual Acuity (BCVA) (Early Treatment of Diabetic Retinopathy Study [ETDRS] Letters) From Baseline to Year 1

Time frame: Baseline and 1 Year

Secondary Outcomes

Mean Change in Central Subfield Thickness (CST) from Baseline to 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.

Time frame: Baseline and Week 52

Mean Change in CST from Baseline Over Time

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 frame: Up to approximately 2 years

Time to Absence of Diabetic Macular Edema (DME) at 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.

Time frame: Up to approximately Week 52

Proportion of Participants with Absence of Intraretinal Fluid Over Time

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.

Time frame: Up to approximately 2 years

Data from ClinicalTrials.gov

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Proportion of Participants with Absence of Subretinal Fluid Over Time

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.

Time frame: Up to approximately 2 years

Proportion of Participants with Absence of Intraretinal Fluid and Subretinal Fluid Over Time

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.

Time frame: Up to approximately 2 years

Proportion of Participants with Diabetic Retinopathy Severity Scale (DRSS) Score Improvement of ≥2 Steps from Baseline to Year 1

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.

Time frame: Baseline and 1 Year

Proportion of Participants with DRSS Score Improvement of ≥3 Steps from Baseline to Year 1

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.

Time frame: Baseline and 1 Year

Proportion of Participants with Resolution of Macular Leakage on Fluorescein Angiography (FA) at 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.

Time frame: Up to approximately Week 24

Mean change in Optical Coherence Tomography (OCT) Central Subfield Thickness (CST) from Baseline to 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.

Time frame: Baseline and Week 104

Proportion of Participants with DRSS Score Improvement of ≥2 Steps from Baseline to Week 104

Time frame: Baseline and Week 104

Proportion of Participants with DRSS Score Improvement of ≥3 Steps from Baseline to 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.

Time frame: Baseline and Week 104

Proportion of Participants Without Retinal Fluid at the Foveal Center on OCT at 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.

Time frame: Up to approximately Week 104

Mean change in Foveal Avascular Zone (FAZ) Area on Fluorescein Angiography (FA) from Baseline to Year 1

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.

Time frame: Baseline and 1 Year

Proportion of Participants with Reduction in FAZ Area on FA from Baseline to Year 1

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.

Time frame: Baseline and 1 Year

Proportion of Participants Without Retinal Fluid at the Foveal Center at 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.

Time frame: Up to approximately Week 52

Mean Number of Intravitreal (IVT) Injections from Week 56 to Week 104

The mean number of intravitreal (IVT) Injections from week 56 to week 104 will be presented.

Time frame: Up to approximately 48 Weeks

Proportion of Participants on a Personalized Treatment Interval (PTI) of every 8 weeks (Q8W) at Week 104

The proportion of participants on a personalized treatment interval (PTI) of every 8 weeks (Q8W) at Week 104 will be presented.

Time frame: Up to approximately Week 104

Proportion of Participants on a Personalized Treatment Interval (PTI) of every 12 weeks (Q12W) at Week 104

The proportion of participants on a personalized treatment interval (PTI) of every 12 weeks (Q12W) at Week 104 will be presented.

Time frame: Up to approximately Week 104

Proportion of Participants on a Personalized Treatment Interval (PTI) of every 16 weeks (Q16W) at Week 104

The proportion of participants on a personalized treatment interval (PTI) of every 16 weeks (Q16W) at Week 104 will be presented.

Time frame: Up to approximately Week 104

Proportion of Participants who Gain ≥5 ETDRS Letters from Baseline to Year 1

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.

Time frame: Baseline and 1 Year

Proportion of Participants who Gain ≥10 ETDRS Letters from Baseline to Year 1

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.

Time frame: Baseline and 1 Year

Proportion of Participants who Gain ≥15 ETDRS Letters from Baseline to Year 1

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.

Time frame: Baseline and 1 Year

Proportion of Participants who Lose ≥5 ETDRS Letters from Baseline to Year 1

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.

Time frame: Baseline and 1 Year

Proportion of Participants who Lose ≥10 ETDRS Letters from Baseline to Year 1

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.

Time frame: Baseline and 1 Year

Proportion of participants who Lose ≥15 ETDRS Letters from Baseline to Year 1

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 frame: Baseline and 1 Year

Time to gain ≥5 ETDRS Letters Over Time

Time frame: Up to approximately 2 years

Time to gain ≥10 ETDRS Letters at Week 52

Time frame: Up to approximately Week 52

Time to gain ≥15 ETDRS letters at Week 52

Time frame: Up to approximately Week 52

Mean Change in BCVA (ETDRS letters) from Baseline Over Time

Time frame: Baseline and 2 Years

Proportion of Participants with BCVA Snellen Equivalent of 20/20 or Better at Year 1

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.

Time frame: Up to approximately 1 year

Proportion of Participants with BCVA Snellen equivalent of 20/200 or Worse at Year 1

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.

Time frame: Up to approximately 1 year

Proportion of Participants with BCVA Snellen Equivalent of 20/40 or Better at Year 1

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.

Time frame: Up to approximately 1 year

Mean Change in BCVA from Baseline to Year 2

Time frame: Baseline and Year 2

Proportion of Participants with BCVA Snellen Equivalent of 20/40 or Better at 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. 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.

Time frame: Up to approximately 2 years

Proportion of Participants with BCVA Snellen Equivalent of 20/200 or Worse at 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. 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.

Time frame: Up to approximately 2 years

Proportion of Participants who Gain ≥5 ETDRS Letters from Baseline to 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. The proportion of participants who gain ≥5 ETDRS Letters from baseline to year 2 will be presented.

Time frame: Baseline and 2 Years

Proportion of Participants who Gain ≥10 ETDRS Letters from Baseline to 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. The proportion of participants who gain ≥10 ETDRS Letters from baseline to year 2 will be presented.

Time frame: Baseline and 2 Years

Proportion of Participants who Gain ≥15 ETDRS Letters from Baseline to 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. The proportion of participants who gain ≥15 ETDRS letters from baseline to year 2 will be presented.

Time frame: Baseline and 2 Years

Proportion of Participants who Lose ≥5 ETDRS Letters from Baseline to Year 2

Time frame: Baseline to 2 Years

Proportion of Participants who Lose ≥10 ETDRS Letters from Baseline to 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. The proportion of participants who lose ≥10 ETDRS letters from baseline to year 2 will be presented.

Time frame: Baseline to 2 Years

Proportion of Participants who Lose ≥15 ETDRS Letters from Baseline to 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. The proportion of participants who lose ≥15 ETDRS Letters from baseline to year 2 will be presented.

Time frame: Baseline and 2 years

Change from Baseline in National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) Version Composite Score at 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.

Time frame: Baseline and Week 48

Change from Baseline in National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) Version Composite Score at Week 104

Time frame: Baseline and Week 104

Number of Participants who Experience a Systemic Adverse Events (AEs)

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.

Time frame: Up to approximately 2 years

Number of Participants who Experience an Ocular Adverse Events (AEs)

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.

Time frame: Up to approximately 2 years

Number of Participants who Discontinue Study Treatment Due to an AE

Time frame: Up to approximately 2 years

Number of Participants with Antidrug Antibodies (ADA) to MK-8748

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.

Time frame: At designated time points (up to approximately 104 weeks)

Maximum Plasma Concentration (Cmax) of MK-8748

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.

Time frame: At designated time points (up to approximately 104 weeks)

Plasma Trough Concentration (Ctrough) of MK-8748

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.

Time frame: At designated time points (up to approximately 104 weeks)