Diabetic Macular Edema
Conditions
Brief summary
Researchers are looking for a better way to treat people who have diabetic macular edema (DME). Diabetic macular edema (DME) is a complication of diabetes. Consistently high blood sugar due to poor glucose control over time can damage small blood vessels in the body, including the eye. Damaged blood vessels in the eye may lead to leakage of the fluid into the central part of the retina at the back of the eye (also called macula) where sharp, straight-ahead vision occurs. Fluid accumulation makes the macula swell and results in reduced vision. If not treated, DME can result in complete loss of central detailed vision. The study treatment intravitreal aflibercept (also called BAY865321) works by blocking VEGFR-1 receptor activity. Intravitreal aflibercept is already approved in over 105 countries for doctors to prescribe to people with DME. In India, aflibercept is approved conditionally for people with DME. The reason for this is that the sponsor was asked to collect more safety data for intravitreal aflibercept in Indian people with DME. The main purpose of this study is to collect more data to learn how safe intravitreal aflibercept is in Indian people with DME. To see how safe intravitreal aflibercept is, the researchers will collect the information/data on the medical problems the participants may have during the study, and which may or may not be related to the study treatment. These medical problems are also known as adverse events (AEs). AEs will be categorized according to relatedness, seriousness, discontinuation of therapy, action taken and outcome. The study participants will receive aflibercept as an injection directly into the space in the back of the eye once every 4 weeks in the first 5 months, followed by one injection every 8 weeks for the rest of the study duration. Only one eye per participant to be treated with aflibercept will be considered for the study. Each participant will be in the study for approximately 52 weeks. The treatment duration will be 48 weeks. For each participant 11 visits to the study site are planned. The study team will perform additional safety calls 16 to 36 hours after each visit starting at visit 2. Alternatively, an additional safety visit can be arranged/planned for the day after treatment. During the study, the study team will: * take blood and urine samples * examine the participants' eyes * do physical examinations * examine heart health using ECG * check vital signs * ask the participants questions about how they are feeling and what adverse events they are having. * in- administer the study drug At the end of the study the participants will be switched to commercially available treatment if recommended by the study doctor/if the participant still benefits from the treatment.
Interventions
DRUGAflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)
Injection, 2mg (equivalent to 50 µL solution for injection)
Sponsors
Bayer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female or male adult participant ≥18 years of age, with type 1 or 2 diabetes mellitus. * Participant must have diabetic macular edema (DME) secondary to diabetes mellitus, involving the centre of the macula (defined as the area of the centre subfield of optical coherence tomography (OCT)) in the study eye. * Decrease in vision, determined to be primarily the result of DME in the study eye. * Retinal thickness of ≥300 µm in the study eye, as assessed by OCT. * Best Corrected Visual Acuity (BCVA) Early Treatment Diabetic Retinopathy Study ( ETDRS) letter score of 73 to 24 (i.e., VA of 20/50 to 20/320) or equivalent in the study eye. * Participant for whom the decision to initiate treatment with Intravitreal (IVT) aflibercept has been made by the treating Investigator/Physician. * Willing and able to comply with clinic visits and study-related procedures. * Provide a signed Informed Consent Form (ICF) prior to any study procedures.
Exclusion criteria
* Having any contraindications to the use of IVT aflibercept as listed in the local prescribing information (i.e., ocular or periocular infection, active severe intraocular inflammation, and known hypersensitivity to aflibercept or to any of the excipients). * History of vitreoretinal surgery and/or scleral buckling in the study eye. * Ocular conditions with a poorer prognosis in the fellow eye than in the study eye. * Received previous/ prior treatment as mentioned below: * Received anti-Vascular Endothelial Growth Factor (VEGF) drugs in the study eye (pegaptanib sodium, bevacizumab, ranibizumab, etc., including aflibercept) within the last 3 months of Day 1. * Received IVT dexamethasone or triamcinolone in the study eye within the last 3 months of Day 1. * Received intraocular or periocular corticosteroids in the study eye within the last 4 months of Day 1. * Had fluocinolone implant in the study eye within the last 3 years of Day 1. * Had dexamethasone implant in the study eye within the last 6 months of Day 1. * systemic anti-angiogenic agents within 6 months of Day 1. * Uncontrolled glaucoma in the study eye (patient who has had filtration surgery in the past, or likely to need filtration surgery in the future). * Only 1 functional eye even if that eye is otherwise eligible for the study. * Participated in an investigational study within 30 days prior to screening visit that involved treatment with any drug (excluding vitamins and minerals) or device. * Pregnant or breast-feeding women.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Frequency (Number) of Ocular and Non-ocular Treatment Emergent Adverse Events (TEAE). | An AE arising or worsening after the start of study treatment administration until 30 days after the last administration of study treatment, up to 52 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Change in BCVA From Baseline to Week 52, as Assessed Using the Early Treatment Diabetic Retinopathy Study (ETDRS) Chart or Equivalent. | From baseline to week 52 | Proportion of eyes that lose ≥ 5, 10 and 15 ETDRS letters from baseline to Week 52, Overall |
| Change in Central Retinal Thickness (CRT) From Baseline to Week 52 as Measured by Optical Coherence Tomography (OCT), FA | From baseline to week 52 | — |
| Proportion of Eyes That Gained ≥ 5, 10 and 15 Early Treatment Diabetic Retinopathy Study (ETDRS) Letters From Baseline to Week 52 | From baseline to Week 52 | Only 1 eye per patient was enrolled in the study. Therefore, number of participants equals to number of eyes. |
| Proportion of Eyes With a ≥2 Step Improvement in the ETDRS Diabetic Retinopathy Severity Scale (DRSS) Score | From baseline to Week 52 | Only 1 eye per patient was enrolled in the study. Therefore, number of participants equals to number of eyes. The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) is a standardized tool used to measure the severity of diabetic retinopathy. The scale assesses the level of retinal damage and provides a score based on the presence of specific lesions and the extent of retinal involvement. Scale Range: * Minimum score: 10 (indicating no retinopathy) * Maximum score: 85 (indicating severe retinopathy) Interpretation of Scores: Higher scores indicate worse outcomes, reflecting more severe diabetic retinopathy |
Countries
India
Participant flow
Recruitment details
The trial was planned to be conducted at approximately 10-15 study sites across India. A total of 100 patients were enrolled into the study. The study duration was up to 13 months covering 11 visits.
Pre-assignment details
121 patients were screened; 21 were screen failures and 100 patients were enrolled in the study: 85 patients in the naïve cohort and 15 patients in the pre-treated cohort
Participants by arm
| Arm | Count |
|---|---|
| Naïve Participants who did not receive any previous/ prior treatment (i.e., participants that previously have not been treated with IVT anti-VEGF or steroids) within the last 3 months of the Day 1 of the study, without laser treatment, and without ocular surgery of the study eye are considered as naive | 85 |
| Pre-Treated Participants who received any previous/ prior treatment for DME (i.e., participants that previously had been treated with IVT anti-VEGF or steroids or laser treatment/ ocular surgery for DME) before the last 3 months of the Day 1 of the study, in the study eye are considered as pre-treated | 15 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall | Death | 1 | 0 |
| Overall | Lost to Follow-up | 3 | 0 |
| Overall | Physician Decision | 3 | 0 |
| Overall | Screen Failure | 20 | 1 |
| Overall | Withdrawal by Subject | 5 | 3 |
| Screening | Lost to Follow Up (1 participant) | 1 | 0 |
| Screening | Screen Failure | 3 | 0 |
| Screening | Screen Failure that was identified after screening (1 participant) | 1 | 0 |
| Screening | Withdrawal by Subject | 1 | 0 |
| Treatment | Death | 1 | 0 |
| Treatment | Lost to Follow-up | 2 | 0 |
| Treatment | Physician Decision | 4 | 0 |
| Treatment | Refuse by subject | 1 | 0 |
| Treatment | Subject did nod visit the site despite multiple follow-up | 3 | 1 |
| Treatment | Subject did not go to the site for visit | 1 | 0 |
| Treatment | Withdrawal by Subject | 5 | 3 |
Baseline characteristics
| Characteristic | Naïve | Total | Pre-Treated |
|---|---|---|---|
| Age, Continuous | 57.6 Years STANDARD_DEVIATION 9.11 | 57.9 Years STANDARD_DEVIATION 9.07 | 59.4 Years STANDARD_DEVIATION 9.01 |
| Body mass Index (kg/m2) | 24.7 Kilograms per meter squared (kg/m2) STANDARD_DEVIATION 3.63 | 24.5 Kilograms per meter squared (kg/m2) STANDARD_DEVIATION 3.57 | 23.3 Kilograms per meter squared (kg/m2) STANDARD_DEVIATION 2.99 |
| Height (cm) | 161.7 Centimeters (cm) STANDARD_DEVIATION 9.18 | 162.0 Centimeters (cm) STANDARD_DEVIATION 9.11 | 163.3 Centimeters (cm) STANDARD_DEVIATION 8.83 |
| Number of patients with at least one medical history finding Cataract | 8 Participants | 11 Participants | 3 Participants |
| Number of patients with at least one medical history finding Diabetic retinal oedema | 83 Participants | 98 Participants | 15 Participants |
| Number of patients with at least one medical history finding Hypertension | 49 Participants | 60 Participants | 11 Participants |
| Number of patients with at least one medical history finding Type 2 diabetes mellitus | 85 Participants | 100 Participants | 15 Participants |
| Race (NIH/OMB) Race American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Race Asian | 85 Participants | 100 Participants | 15 Participants |
| Race (NIH/OMB) Race Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Race More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Race Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Race Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Race White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Sex Female | 41 Participants | 45 Participants | 4 Participants |
| Sex: Female, Male Sex Male | 44 Participants | 55 Participants | 11 Participants |
| Weight (kg) | 64.8 kilograms (kg) STANDARD_DEVIATION 11.38 | 64.5 kilograms (kg) STANDARD_DEVIATION 11.31 | 62.4 kilograms (kg) STANDARD_DEVIATION 11.12 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 1 / 85 | 0 / 15 | 1 / 85 | 0 / 15 | 1 / 85 | 0 / 15 | 1 / 85 | 0 / 15 | 1 / 85 |
| other Total, other adverse events | 11 / 15 | 42 / 85 | 9 / 15 | 31 / 85 | 5 / 15 | 17 / 85 | 7 / 15 | 12 / 85 | 3 / 15 | 22 / 85 |
| serious Total, serious adverse events | 0 / 15 | 4 / 85 | 0 / 15 | 0 / 85 | 0 / 15 | 4 / 85 | 0 / 15 | 0 / 85 | 0 / 15 | 0 / 85 |
Outcome results
Primary
Frequency (Number) of Ocular and Non-ocular Treatment Emergent Adverse Events (TEAE).
Time frame: An AE arising or worsening after the start of study treatment administration until 30 days after the last administration of study treatment, up to 52 weeks.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Naïve | Frequency (Number) of Ocular and Non-ocular Treatment Emergent Adverse Events (TEAE). | Ocular | 36.5 Percentage of participants |
| Naïve | Frequency (Number) of Ocular and Non-ocular Treatment Emergent Adverse Events (TEAE). | Non-Ocular | 21.2 Percentage of participants |
| Pre-Treated | Frequency (Number) of Ocular and Non-ocular Treatment Emergent Adverse Events (TEAE). | Ocular | 60 Percentage of participants |
| Pre-Treated | Frequency (Number) of Ocular and Non-ocular Treatment Emergent Adverse Events (TEAE). | Non-Ocular | 33.3 Percentage of participants |
| Total | Frequency (Number) of Ocular and Non-ocular Treatment Emergent Adverse Events (TEAE). | Ocular | 40 Percentage of participants |
| Total | Frequency (Number) of Ocular and Non-ocular Treatment Emergent Adverse Events (TEAE). | Non-Ocular | 23 Percentage of participants |
Secondary
Change in Central Retinal Thickness (CRT) From Baseline to Week 52 as Measured by Optical Coherence Tomography (OCT), FA
Time frame: From baseline to week 52
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naïve | Change in Central Retinal Thickness (CRT) From Baseline to Week 52 as Measured by Optical Coherence Tomography (OCT), FA | -203.5 um | Standard Deviation 148.19 |
| Pre-Treated | Change in Central Retinal Thickness (CRT) From Baseline to Week 52 as Measured by Optical Coherence Tomography (OCT), FA | -160.3 um | Standard Deviation 127.42 |
| Total | Change in Central Retinal Thickness (CRT) From Baseline to Week 52 as Measured by Optical Coherence Tomography (OCT), FA | -197.4 um | Standard Deviation 145.63 |
Secondary
Proportion of Eyes That Gained ≥ 5, 10 and 15 Early Treatment Diabetic Retinopathy Study (ETDRS) Letters From Baseline to Week 52
Only 1 eye per patient was enrolled in the study. Therefore, number of participants equals to number of eyes.
Time frame: From baseline to Week 52
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Naïve | Proportion of Eyes That Gained ≥ 5, 10 and 15 Early Treatment Diabetic Retinopathy Study (ETDRS) Letters From Baseline to Week 52 | ≥10 ETDRS letters | 63 Participants |
| Naïve | Proportion of Eyes That Gained ≥ 5, 10 and 15 Early Treatment Diabetic Retinopathy Study (ETDRS) Letters From Baseline to Week 52 | ≥5 ETDRS letters | 76 Participants |
| Naïve | Proportion of Eyes That Gained ≥ 5, 10 and 15 Early Treatment Diabetic Retinopathy Study (ETDRS) Letters From Baseline to Week 52 | ≥15 ETDRS letters | 43 Participants |
| Pre-Treated | Proportion of Eyes That Gained ≥ 5, 10 and 15 Early Treatment Diabetic Retinopathy Study (ETDRS) Letters From Baseline to Week 52 | ≥10 ETDRS letters | 11 Participants |
| Pre-Treated | Proportion of Eyes That Gained ≥ 5, 10 and 15 Early Treatment Diabetic Retinopathy Study (ETDRS) Letters From Baseline to Week 52 | ≥5 ETDRS letters | 11 Participants |
| Pre-Treated | Proportion of Eyes That Gained ≥ 5, 10 and 15 Early Treatment Diabetic Retinopathy Study (ETDRS) Letters From Baseline to Week 52 | ≥15 ETDRS letters | 7 Participants |
| Total | Proportion of Eyes That Gained ≥ 5, 10 and 15 Early Treatment Diabetic Retinopathy Study (ETDRS) Letters From Baseline to Week 52 | ≥5 ETDRS letters | 87 Participants |
| Total | Proportion of Eyes That Gained ≥ 5, 10 and 15 Early Treatment Diabetic Retinopathy Study (ETDRS) Letters From Baseline to Week 52 | ≥15 ETDRS letters | 50 Participants |
| Total | Proportion of Eyes That Gained ≥ 5, 10 and 15 Early Treatment Diabetic Retinopathy Study (ETDRS) Letters From Baseline to Week 52 | ≥10 ETDRS letters | 74 Participants |
Secondary
Proportion of Eyes With a ≥2 Step Improvement in the ETDRS Diabetic Retinopathy Severity Scale (DRSS) Score
Only 1 eye per patient was enrolled in the study. Therefore, number of participants equals to number of eyes. The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) is a standardized tool used to measure the severity of diabetic retinopathy. The scale assesses the level of retinal damage and provides a score based on the presence of specific lesions and the extent of retinal involvement. Scale Range: * Minimum score: 10 (indicating no retinopathy) * Maximum score: 85 (indicating severe retinopathy) Interpretation of Scores: Higher scores indicate worse outcomes, reflecting more severe diabetic retinopathy
Time frame: From baseline to Week 52
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Naïve | Proportion of Eyes With a ≥2 Step Improvement in the ETDRS Diabetic Retinopathy Severity Scale (DRSS) Score | 12 Participants |
| Pre-Treated | Proportion of Eyes With a ≥2 Step Improvement in the ETDRS Diabetic Retinopathy Severity Scale (DRSS) Score | 3 Participants |
| Total | Proportion of Eyes With a ≥2 Step Improvement in the ETDRS Diabetic Retinopathy Severity Scale (DRSS) Score | 15 Participants |
Secondary
The Change in BCVA From Baseline to Week 52, as Assessed Using the Early Treatment Diabetic Retinopathy Study (ETDRS) Chart or Equivalent.
Proportion of eyes that lose ≥ 5, 10 and 15 ETDRS letters from baseline to Week 52, Overall
Time frame: From baseline to week 52
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Naïve | The Change in BCVA From Baseline to Week 52, as Assessed Using the Early Treatment Diabetic Retinopathy Study (ETDRS) Chart or Equivalent. | ≥ 10 ETDRS letters | 2.4 Percentage of eyes |
| Naïve | The Change in BCVA From Baseline to Week 52, as Assessed Using the Early Treatment Diabetic Retinopathy Study (ETDRS) Chart or Equivalent. | ≥ 5 ETDRS letters | 2.4 Percentage of eyes |
| Naïve | The Change in BCVA From Baseline to Week 52, as Assessed Using the Early Treatment Diabetic Retinopathy Study (ETDRS) Chart or Equivalent. | ≥ 15 ETDRS letters | 2.4 Percentage of eyes |
| Pre-Treated | The Change in BCVA From Baseline to Week 52, as Assessed Using the Early Treatment Diabetic Retinopathy Study (ETDRS) Chart or Equivalent. | ≥ 10 ETDRS letters | 0 Percentage of eyes |
| Pre-Treated | The Change in BCVA From Baseline to Week 52, as Assessed Using the Early Treatment Diabetic Retinopathy Study (ETDRS) Chart or Equivalent. | ≥ 5 ETDRS letters | 7.1 Percentage of eyes |
| Pre-Treated | The Change in BCVA From Baseline to Week 52, as Assessed Using the Early Treatment Diabetic Retinopathy Study (ETDRS) Chart or Equivalent. | ≥ 15 ETDRS letters | 0 Percentage of eyes |
| Total | The Change in BCVA From Baseline to Week 52, as Assessed Using the Early Treatment Diabetic Retinopathy Study (ETDRS) Chart or Equivalent. | ≥ 5 ETDRS letters | 3 Percentage of eyes |
| Total | The Change in BCVA From Baseline to Week 52, as Assessed Using the Early Treatment Diabetic Retinopathy Study (ETDRS) Chart or Equivalent. | ≥ 15 ETDRS letters | 2 Percentage of eyes |
| Total | The Change in BCVA From Baseline to Week 52, as Assessed Using the Early Treatment Diabetic Retinopathy Study (ETDRS) Chart or Equivalent. | ≥ 10 ETDRS letters | 2 Percentage of eyes |