Age-related Macular Degeneration
Conditions
Keywords
Age-related macular degeneration,, ranibizumab,, conbercept,, plasma VEGF, PK
Brief summary
An exploratory single site, open label, randomized, controlled study evaluated plasma vascular endothelial growth factor levels after intravitreal injection of ranibizumab (Lucentis) and conbercept (Langmu) for neovascular age-related macular degeneration
Detailed description
This prospective, randomized, open label study enrolled patients with neovascular AMD who were naïve to anti-VEGF therapy or have not received intravitreal anti-VEGF therapy for the previous 3 months. Patients were randomized in two treatment arms for 3 months: * Study arm 1: Three monthly injections of 0.5mg Ranibizumab * Study arm 2: Three monthly injections of 0.5mg Conbercept Blood sample (plasma/serum) was collected at baseline (pre-dose), 3h post-injections and days 1, 3, 7 and 28, following doses 1 and 3 for PK and systemic VEGF analysis. The lab staff was blinded for treatment allocation. Plasma VEGF concentration was measured by a blinded laboratory using Quantikine® ELISA kits. Serum ranibizumab and conbercept concentration will be determined using validated ELISA assay. The study was divided into 2 stages: the 1st initial feasibility stage with 6 patients per arm (12 patients in total) to verify SD for sample size justification and 2nd stage to confirm the findings with justified sample size.
Interventions
DRUGranibizumab
DRUGConbercept
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
1. Written informed consent must be obtained before any assessment is performed. 2. Male or female patient ≥ 50 years of age. 3. Subfoveal CNV secondary to nAMD. 4. BCVA score must be between 73 and 24 letters as measured by ETDRS chart
Exclusion criteria
For both eyes 1. Any active periocular or ocular infection or inflammation 2. Uncontrolled glaucoma 3. Neovascularization of the iris or neovascular glaucoma. For study eye 4. Choroidal neovascularization of any other cause than wet AMD 5. Ocular disorders present that may confound interpretation of study results, 6. Previous treatment with verteporfin PDT (Visudyne®), external-beam radiation therapy, focal laser photocoagulation, vitrectomy, submacular surgery, or transpupillary thermotherapy. 7. Structural damage within 0.5 disc diameter of the center of the macula 8. Atrophy or fibrosis involving the center of the fovea. 9. Inability of obtaining required lab report. Ocular medical history 10. History of intravitreal injection with any anti-VEGF drugs within 3 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentration After First Injection at Visit 5 (Day 8 +/- 1 Day) | Baseline, Visit 5 (Day 8 +/- 1 day) | Change from baseline in plasma Vascular endothelial growth factor (VEGF) concentration after first injection at Visit 5 (Day 8 +/- 1 day).Blood sample was collected for systemic VEGF. VEGF was measured by a blinded laboratory using ELISA kits. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentration After Third Injection at Visit 10 (Day 67 +/- 1 Day) | Baseline, Visit 10 (Day 67 +/- 1 day) | Change from baseline in plasma Vascular endothelial growth factor (VEGF) concentration after third injection at Visit 10 (Day 67 +/- 1 day). Blood sample was collected for systemic VEGF. VEGF will be measured by a blinded laboratory using ELISA kits. |
| Plasma VEGF Concentration at Baseline, Visit 2, 3, 4, 5, 6 After 1st Injection | Baseline, Visit 2, 3, 4, 5, 6 | Blood sample will be collected for systemic VEGF. VEGF will be measured by a blinded laboratory using ELISA kits. Baseline, Visit Visit 2, 3, 4, 5, 6 after 1st injection |
| Plasma VEGF Concentration at Baseline, Visit 7, 8, 9, 10, 11 After 3rd Injection | Baseline, Visit 7, 8, 9, 10, 11 | Blood sample will be collected for systemic VEGF. VEGF will be measured by a blinded laboratory using ELISA kits. Baseline, Visit 7, 8, 9, 10, 11 after 3rd injection |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ranibizumab 0.5 mg Three monthly injections of 0.5mg Ranibizumab | 6 |
| Conbercept 0.5 mg Three monthly injections of 0.5mg Conbercept | 6 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol deviation | 0 | 1 |
Baseline characteristics
| Characteristic | Ranibizumab 0.5 mg | Conbercept 0.5 mg | Total |
|---|---|---|---|
| Age, Continuous | 65.3 years STANDARD_DEVIATION 5.5 | 69.3 years STANDARD_DEVIATION 8.41 | 67.3 years STANDARD_DEVIATION 7.09 |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 6 | 3 / 6 |
| serious Total, serious adverse events | 0 / 6 | 2 / 6 |
Outcome results
Primary
Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentration After First Injection at Visit 5 (Day 8 +/- 1 Day)
Change from baseline in plasma Vascular endothelial growth factor (VEGF) concentration after first injection at Visit 5 (Day 8 +/- 1 day).Blood sample was collected for systemic VEGF. VEGF was measured by a blinded laboratory using ELISA kits.
Time frame: Baseline, Visit 5 (Day 8 +/- 1 day)
Population: Per-protocol Set refers to all subjects who completed the study without any major deviation from the study protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ranibizumab 0.5 mg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentration After First Injection at Visit 5 (Day 8 +/- 1 Day) | 5.720 pg/mL | Standard Deviation 9.5547 |
| Conbercept 0.5 mg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentration After First Injection at Visit 5 (Day 8 +/- 1 Day) | -25.833 pg/mL | Standard Deviation 22.8145 |
95% CI: [9.618, 31.011]
Secondary
Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentration After Third Injection at Visit 10 (Day 67 +/- 1 Day)
Change from baseline in plasma Vascular endothelial growth factor (VEGF) concentration after third injection at Visit 10 (Day 67 +/- 1 day). Blood sample was collected for systemic VEGF. VEGF will be measured by a blinded laboratory using ELISA kits.
Time frame: Baseline, Visit 10 (Day 67 +/- 1 day)
Population: Per-protocol Set refers to all subjects who completed the study without any major deviation from the study protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ranibizumab 0.5 mg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentration After Third Injection at Visit 10 (Day 67 +/- 1 Day) | -0.100 pg/mL | Standard Deviation 17.4799 |
| Conbercept 0.5 mg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentration After Third Injection at Visit 10 (Day 67 +/- 1 Day) | -22.220 pg/mL | Standard Deviation 12.9239 |
Secondary
Plasma VEGF Concentration at Baseline, Visit 2, 3, 4, 5, 6 After 1st Injection
Blood sample will be collected for systemic VEGF. VEGF will be measured by a blinded laboratory using ELISA kits. Baseline, Visit Visit 2, 3, 4, 5, 6 after 1st injection
Time frame: Baseline, Visit 2, 3, 4, 5, 6
Population: Per-protocol Set refers to all subjects who completed the study without any major deviation from the study protocol.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ranibizumab 0.5 mg | Plasma VEGF Concentration at Baseline, Visit 2, 3, 4, 5, 6 After 1st Injection | Baseline | 31.400 pg/mL | Standard Deviation 6.3816 |
| Ranibizumab 0.5 mg | Plasma VEGF Concentration at Baseline, Visit 2, 3, 4, 5, 6 After 1st Injection | Visit 2 (Day 1) | 30.958 pg/mL | Standard Deviation 19.9813 |
| Ranibizumab 0.5 mg | Plasma VEGF Concentration at Baseline, Visit 2, 3, 4, 5, 6 After 1st Injection | Visit 3 (Day 2 +/- 1) | 36.517 pg/mL | Standard Deviation 19.2783 |
| Ranibizumab 0.5 mg | Plasma VEGF Concentration at Baseline, Visit 2, 3, 4, 5, 6 After 1st Injection | Visit 4 (Day 4 +/- 1) | 29.150 pg/mL | Standard Deviation 5.5587 |
| Ranibizumab 0.5 mg | Plasma VEGF Concentration at Baseline, Visit 2, 3, 4, 5, 6 After 1st Injection | Visit 5 (Day 8 +/- 1) | 37.000 pg/mL | Standard Deviation 4.7979 |
| Ranibizumab 0.5 mg | Plasma VEGF Concentration at Baseline, Visit 2, 3, 4, 5, 6 After 1st Injection | Visit 6 (Day 30 +/- 4) | 27.092 pg/mL | Standard Deviation 13.2356 |
| Conbercept 0.5 mg | Plasma VEGF Concentration at Baseline, Visit 2, 3, 4, 5, 6 After 1st Injection | Visit 5 (Day 8 +/- 1) | 19.075 pg/mL | Standard Deviation 4.5051 |
| Conbercept 0.5 mg | Plasma VEGF Concentration at Baseline, Visit 2, 3, 4, 5, 6 After 1st Injection | Baseline | 42.200 pg/mL | Standard Deviation 23.4269 |
| Conbercept 0.5 mg | Plasma VEGF Concentration at Baseline, Visit 2, 3, 4, 5, 6 After 1st Injection | Visit 4 (Day 4 +/- 1) | 7.213 pg/mL | Standard Deviation 4.925 |
| Conbercept 0.5 mg | Plasma VEGF Concentration at Baseline, Visit 2, 3, 4, 5, 6 After 1st Injection | Visit 2 (Day 1) | 14.920 pg/mL | Standard Deviation 12.492 |
| Conbercept 0.5 mg | Plasma VEGF Concentration at Baseline, Visit 2, 3, 4, 5, 6 After 1st Injection | Visit 6 (Day 30 +/- 4) | 25.270 pg/mL | Standard Deviation 15.0967 |
| Conbercept 0.5 mg | Plasma VEGF Concentration at Baseline, Visit 2, 3, 4, 5, 6 After 1st Injection | Visit 3 (Day 2 +/- 1) | 24.590 pg/mL | Standard Deviation 39.2435 |
Secondary
Plasma VEGF Concentration at Baseline, Visit 7, 8, 9, 10, 11 After 3rd Injection
Blood sample will be collected for systemic VEGF. VEGF will be measured by a blinded laboratory using ELISA kits. Baseline, Visit 7, 8, 9, 10, 11 after 3rd injection
Time frame: Baseline, Visit 7, 8, 9, 10, 11
Population: Per-protocol Set refers to all subjects who completed the study without any major deviation from the study protocol.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ranibizumab 0.5 mg | Plasma VEGF Concentration at Baseline, Visit 7, 8, 9, 10, 11 After 3rd Injection | Visit 7 (Day 60 +/- 4) | 34.383 pg/mL | Standard Deviation 12.7727 |
| Ranibizumab 0.5 mg | Plasma VEGF Concentration at Baseline, Visit 7, 8, 9, 10, 11 After 3rd Injection | Visit 9 (Day 63 +/- 1) | 54.067 pg/mL | Standard Deviation 40.2585 |
| Ranibizumab 0.5 mg | Plasma VEGF Concentration at Baseline, Visit 7, 8, 9, 10, 11 After 3rd Injection | Baseline | 36.250 pg/mL | Standard Deviation 11.861 |
| Ranibizumab 0.5 mg | Plasma VEGF Concentration at Baseline, Visit 7, 8, 9, 10, 11 After 3rd Injection | Visit 10 (Day 67 +/- 1) | 36.150 pg/mL | Standard Deviation 25.4399 |
| Ranibizumab 0.5 mg | Plasma VEGF Concentration at Baseline, Visit 7, 8, 9, 10, 11 After 3rd Injection | Visit 8 (Day 61 +/- 1) | 46.533 pg/mL | Standard Deviation 48.1293 |
| Ranibizumab 0.5 mg | Plasma VEGF Concentration at Baseline, Visit 7, 8, 9, 10, 11 After 3rd Injection | Visit 11 (Day 90 +/- 4) | 45.067 pg/mL | Standard Deviation 18.0828 |
| Conbercept 0.5 mg | Plasma VEGF Concentration at Baseline, Visit 7, 8, 9, 10, 11 After 3rd Injection | Visit 8 (Day 61 +/- 1) | 6.820 pg/mL | Standard Deviation 4.6287 |
| Conbercept 0.5 mg | Plasma VEGF Concentration at Baseline, Visit 7, 8, 9, 10, 11 After 3rd Injection | Baseline | 36.520 pg/mL | Standard Deviation 19.2278 |
| Conbercept 0.5 mg | Plasma VEGF Concentration at Baseline, Visit 7, 8, 9, 10, 11 After 3rd Injection | Visit 7 (Day 60 +/- 4) | 5.720 pg/mL | Standard Deviation 2.169 |
| Conbercept 0.5 mg | Plasma VEGF Concentration at Baseline, Visit 7, 8, 9, 10, 11 After 3rd Injection | Visit 11 (Day 90 +/- 4) | 56.020 pg/mL | Standard Deviation 27.0819 |
| Conbercept 0.5 mg | Plasma VEGF Concentration at Baseline, Visit 7, 8, 9, 10, 11 After 3rd Injection | Visit 9 (Day 63 +/- 1) | 8.070 pg/mL | Standard Deviation 4.6452 |
| Conbercept 0.5 mg | Plasma VEGF Concentration at Baseline, Visit 7, 8, 9, 10, 11 After 3rd Injection | Visit 10 (Day 67 +/- 1) | 14.300 pg/mL | Standard Deviation 9.669 |