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

Browse trials for

• Diabetic Retinopathy 767
• Macular Edema 842

Keywords

• Diabetic Macular Edema (DME)

Study arms

• Experimental
  MK-8748 Low Dose

  Participants receive 5 initial administrations of MK-8748 low dose every 4 weeks (Q4W), then continue to receive MK-8748 low dose every 8 weeks (Q8W) until week 48. After week 48, participants will be treated at intervals determined based on individualized response to treatment, up to week 100.

  Drug: MK-8748

• Experimental
  MK-8748 High Dose

  Participants receive 5 initial administrations of MK-8748 high dose every 4 weeks (Q4W), then continue to receive MK-8748 high dose every 8 weeks (Q8W) until week 48. After week 48, participants will be treated at intervals determined based on individualized response to treatment, up to week 100.

  Drug: MK-8748

• Active comparator
  Aflibercept 2 mg

  Participants receive 5 initial administrations of aflibercept 2 mg every 4 weeks (Q4W), then continue to receive aflibercept 2mg every 8 weeks (Q8W) until week 100.

  Drug: Aflibercept

Interventions

• DrugMK-8748

  Administered by intravitreal injection (IVT)

  Also known as: EYE201, Tiespectus

• DrugAflibercept

  Administered by intravitreal injection (IVT)

  Also known as: Eylea

Primary outcomes

1. Mean Change in Best-Corrected Visual Acuity (BCVA) (Early Treatment of Diabetic Retinopathy Study [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. Mean change in ETDRS letters from baseline to Year 1 will be assessed.

   Time frame: Baseline and 1 Year

Secondary outcomes

1. 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

2. 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

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

11. Proportion of Participants with DRSS Score Improvement of ≥2 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 ≥2 step improvement in DRSS score from baseline to week 104 will be presented.

    Time frame: Baseline and Week 104

12. 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

13. 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

14. 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

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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

22. 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

23. 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

24. 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

25. 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

26. 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

27. Time to gain ≥5 ETDRS Letters Over Time

    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 frame: Up to approximately 2 years

28. Time to gain ≥10 ETDRS Letters at 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 frame: Up to approximately Week 52

29. Time to gain ≥15 ETDRS letters at 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.

    Time frame: Up to approximately Week 52

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

    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.

    Time frame: Baseline and 2 Years

31. 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

32. 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

33. 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

34. Mean Change in BCVA 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. Mean change in ETDRS letters from baseline to year 2 will be assessed.

    Time frame: Baseline and Year 2

35. 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

36. 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

37. 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

38. 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

39. 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

40. Proportion of Participants who Lose ≥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 lose ≥5 ETDRS Letters baseline to year 2 will be presented.

    Time frame: Baseline to 2 Years

41. 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

42. 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

43. 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

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

    Time frame: Baseline and Week 104

45. 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

46. 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

47. Number of Participants who Discontinue Study Treatment Due to an AE

    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.

    Time frame: Up to approximately 2 years

48. 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)

49. 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)

50. 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)

Related links

• Merck Clinical Trials Information ↗

Individual participant data

Plan to share: Yes — https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf