Diabetic Macular Edema (DME)
Conditions
Brief summary
This is a Randomized, Active-Controlled, Double-Masked, Parallel-Group, Phase 3 Study to Compare Efficacy and Safety of CT-P42 in comparison with Eylea in Patients with Diabetic Macular Edema
Interventions
BIOLOGICALCT-P42
2mg/0.05 mL by Intravitreal injection
BIOLOGICALEylea
2mg/0.05 mL by Intravitreal injection
Sponsors
Celltrion
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female patient aged ≥18 years. * Patient with DME secondary to DM involving the center of the macula (defined as the Optical Coherence Tomography \[OCT\] central subfield) in the study eye.
Exclusion criteria
* Patient who has only one functional eye. * Patient who currently has, or has a history (where indicated) of active proliferative diabetic retinopathy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 8 | Baseline and Week 8 | Mean change from baseline in BCVA as assessed by Early Treatment Diabetic Retinopathy Study (ETDRS) letters at week 8. Subjects with a BCVA ETDRS letter score of 73 to 34 (= Acuity of 20/40 to 20/200) in the study eye at Screening and Day 1 were included. Visual acuity of the study eye was assessed using the ETDRS charts; a higher score represents better functioning. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in BCVA at Week 52 | Baseline and Week 52 | Mean change from baseline in BCVA as assessed by Early Treatment Diabetic Retinopathy Study (ETDRS) letters at week 52. |
| Proportion of Subjects Who Gained ≥15 Letters in BCVA as Measured by ETDRS Letter Score Compared With Baseline at Week 52 | Baseline and Week 52 | Proportion of subjects who gained ≥15 letters from baseline in BCVA, assessed in change from baseline in ETDRS letters over time |
| Proportion of Subjects With a ≥2-step Improvement From Baseline in the ETDRS DRSS (Diabetic Retinopathy Severity Score) as Assessed by FP (Fundus Photography) at Week 52 | Baseline and Week 52 | The ETDRS DRSS score was grouped into 13 severity scores based on the ETDRS Severity Level. DR absent (level 10); Mild to moderate nonproliferative DR (levels 20, 35, and 43); Moderately severe/severe/Very Severe nonproliferative DR (levels 47, 53 and 53E); Inactive/Mild/moderate/high-risk/advanced proliferative DR (levels 60, 61, 65, 71,75, 81, and 85) |
| Change From Baseline in Central Subfield Thickness (CST) at Week 52 as Assessed on Optical Coherence Tomography (OCT) | Baseline and Week 52 | The mean change from baseline in Central Subfieldl Thickness as determined by Spectral domain- Optical coherence tomography (SD-OCT) |
Countries
Slovakia
Participant flow
Pre-assignment details
Subjects who were randomly assigned to either group administrated study drug by intravitreal injection (IVT) via a sigle-dose vial every 4 weeks for 5 doses, then every 8 weeks for 4 doses up to Week 48. After the Main Study period, a total of 31 subjects, regardless of the treatment group in Main Study Period, were enrolled in a 4-week open-label, single-arm Extension study. The subjects were administrated 2 mg/0.05mL of CT-P42 by pre-filled syringe IVT injection at Extension Week 0 (1 dose).
Participants by arm
| Arm | Count |
|---|---|
| CT-P42 CT-P42: 2mg/0.05 mL by Intravitreal injection | 173 |
| Eylea Eylea: 2mg/0.05 mL by Intravitreal injection | 175 |
| Total | 348 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Main Study Period | Adverse Event | 6 | 7 |
| Main Study Period | Lost to Follow-up | 4 | 6 |
| Main Study Period | Physician Decision | 1 | 1 |
| Main Study Period | Protocol Violation | 0 | 1 |
| Main Study Period | War in Ukraine | 1 | 1 |
| Main Study Period | Withdrawal by Subject | 8 | 6 |
Baseline characteristics
| Characteristic | CT-P42 | Total | Eylea |
|---|---|---|---|
| Age, Continuous | 62.5 years STANDARD_DEVIATION 9.6 | 62.7 years STANDARD_DEVIATION 10 | 62.9 years STANDARD_DEVIATION 10.3 |
| BCVA score at Baseline | 60.3 letters STANDARD_DEVIATION 9.7 | 60.4 letters STANDARD_DEVIATION 9.9 | 60.4 letters STANDARD_DEVIATION 10.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 10 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 166 Participants | 331 Participants | 165 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 7 Participants | 5 Participants |
| Race/Ethnicity, Customized Asian | 61 Participants | 124 Participants | 63 Participants |
| Race/Ethnicity, Customized White | 112 Participants | 224 Participants | 112 Participants |
| Region of Enrollment Czechia | 19 participants | 37 participants | 18 participants |
| Region of Enrollment Estonia | 1 participants | 2 participants | 1 participants |
| Region of Enrollment Hungary | 21 participants | 41 participants | 20 participants |
| Region of Enrollment India | 51 participants | 104 participants | 53 participants |
| Region of Enrollment Latvia | 9 participants | 14 participants | 5 participants |
| Region of Enrollment Lithuania | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Poland | 19 participants | 40 participants | 21 participants |
| Region of Enrollment Russia | 6 participants | 14 participants | 8 participants |
| Region of Enrollment Slovakia | 24 participants | 47 participants | 23 participants |
| Region of Enrollment South Korea | 10 participants | 20 participants | 10 participants |
| Region of Enrollment Spain | 8 participants | 17 participants | 9 participants |
| Region of Enrollment Ukraine | 5 participants | 11 participants | 6 participants |
| Sex: Female, Male Female | 67 Participants | 145 Participants | 78 Participants |
| Sex: Female, Male Male | 106 Participants | 203 Participants | 97 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 174 | 2 / 174 | 0 / 31 |
| other Total, other adverse events | 64 / 174 | 71 / 174 | 3 / 31 |
| serious Total, serious adverse events | 19 / 174 | 17 / 174 | 0 / 31 |
Outcome results
Primary
Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 8
Mean change from baseline in BCVA as assessed by Early Treatment Diabetic Retinopathy Study (ETDRS) letters at week 8. Subjects with a BCVA ETDRS letter score of 73 to 34 (= Acuity of 20/40 to 20/200) in the study eye at Screening and Day 1 were included. Visual acuity of the study eye was assessed using the ETDRS charts; a higher score represents better functioning.
Time frame: Baseline and Week 8
Population: Full analysis set (FAS) consists of all subjects who are randomly assigned and received at least 1 full dose of study drug during the Main Study Period. Missing data were not imputed unless methods for handling missing data are specified.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CT-P42 | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 8 | 9.43 letters | Standard Error 0.798 |
| Eylea | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 8 | 8.85 letters | Standard Error 0.775 |
90% CI: [-0.52, 1.67]ANCOVA
Secondary
Change From Baseline in Central Subfield Thickness (CST) at Week 52 as Assessed on Optical Coherence Tomography (OCT)
The mean change from baseline in Central Subfieldl Thickness as determined by Spectral domain- Optical coherence tomography (SD-OCT)
Time frame: Baseline and Week 52
Population: Full analysis set (subjects analysed at Week 52). Missing data were not imputed unless methods for handling missing data are specified.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CT-P42 | Change From Baseline in Central Subfield Thickness (CST) at Week 52 as Assessed on Optical Coherence Tomography (OCT) | -220.7 micrometer | Standard Deviation 147.1 |
| Eylea | Change From Baseline in Central Subfield Thickness (CST) at Week 52 as Assessed on Optical Coherence Tomography (OCT) | -191.2 micrometer | Standard Deviation 137 |
Secondary
Mean Change From Baseline in BCVA at Week 52
Mean change from baseline in BCVA as assessed by Early Treatment Diabetic Retinopathy Study (ETDRS) letters at week 52.
Time frame: Baseline and Week 52
Population: Full analysis set (subjects analysed at Week 52). Missing data were not imputed unless methods for handling missing data are specified.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CT-P42 | Mean Change From Baseline in BCVA at Week 52 | 12.1 letters | Standard Deviation 8.9 |
| Eylea | Mean Change From Baseline in BCVA at Week 52 | 11.1 letters | Standard Deviation 9.9 |
Secondary
Proportion of Subjects Who Gained ≥15 Letters in BCVA as Measured by ETDRS Letter Score Compared With Baseline at Week 52
Proportion of subjects who gained ≥15 letters from baseline in BCVA, assessed in change from baseline in ETDRS letters over time
Time frame: Baseline and Week 52
Population: Full analysis set. Missing data were not imputed unless methods for handling missing data are specified.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CT-P42 | Proportion of Subjects Who Gained ≥15 Letters in BCVA as Measured by ETDRS Letter Score Compared With Baseline at Week 52 | 60 Participants |
| Eylea | Proportion of Subjects Who Gained ≥15 Letters in BCVA as Measured by ETDRS Letter Score Compared With Baseline at Week 52 | 52 Participants |
Secondary
Proportion of Subjects With a ≥2-step Improvement From Baseline in the ETDRS DRSS (Diabetic Retinopathy Severity Score) as Assessed by FP (Fundus Photography) at Week 52
The ETDRS DRSS score was grouped into 13 severity scores based on the ETDRS Severity Level. DR absent (level 10); Mild to moderate nonproliferative DR (levels 20, 35, and 43); Moderately severe/severe/Very Severe nonproliferative DR (levels 47, 53 and 53E); Inactive/Mild/moderate/high-risk/advanced proliferative DR (levels 60, 61, 65, 71,75, 81, and 85)
Time frame: Baseline and Week 52
Population: Full analysis set. Missing data were not imputed unless methods for handling missing data are specified.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CT-P42 | Proportion of Subjects With a ≥2-step Improvement From Baseline in the ETDRS DRSS (Diabetic Retinopathy Severity Score) as Assessed by FP (Fundus Photography) at Week 52 | 41 Participants |
| Eylea | Proportion of Subjects With a ≥2-step Improvement From Baseline in the ETDRS DRSS (Diabetic Retinopathy Severity Score) as Assessed by FP (Fundus Photography) at Week 52 | 38 Participants |