Glaucoma, Neovascular
Conditions
Brief summary
To assess the efficacy and safety of the administration of aflibercept by intravitreal injection in comparison to sham to control intraocular pressure in patients with neovascular glaucoma.
Interventions
DRUGAflibercept (Eylea, BAY 86-5321)
After the first aflibercept IVT injection on Day 1, subjects may receive sham injection at Week 1, and aflibercept injection at Week 5 and/or Week 9 if the re-treatment criteria are met.
DRUGSham Injection
After the first sham injection on Day 1, subjects may receive aflibercept IVT injection at Week 1, Week 5 and/or Week 9 if re-treatment criteria are met.
Sponsors
Regeneron Pharmaceuticals
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Japanese men and women aged 20 years or older, * Patients diagnosed as having Neovascular glaucoma (NVG) with neovascularization in the anterior segment (both iris and anterior chamber angle), * Patients with Intraocular pressure (IOP) higher than 25 mmHg in the study eye due to anterior segment (both iris and anterior chamber angle) neovascularization.
Exclusion criteria
* Patients with angle-closure due to conditions other than Neovascular glaucoma * Patients with a known or suspected ocular or peri-ocular infection, * Patients with severe intraocular inflammation in the study eye, * Women who are pregnant, suspected of being pregnant or lactating, * Patients with known allergy to aflibercept.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Intraocular Pressure (IOP) From Baseline to Pre-dose at Week 1 | From baseline to pre-dose at Week 1 | It compared the change in IOP from baseline to pre-dose at Week 1 between the aflibercept group vs the sham group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Who Had Improved Neovascularization of the Iris (NVI) Grade From Baseline to Pre-dose at Week 1 | From baseline to pre-dose at Week 1 | NVI were assessed in the study eye using the NVI grading systems (grade 0 to grade 4). A subject who shows the improvement by at least one grade is considered to be improved. Percentage of subjects who had improved NVI grade was reported. |
Countries
Japan
Participant flow
Recruitment details
Study was conducted at nineteen study centers in Japan, between 02 April 2015 (first subject first visit) and 06 Sep 2016 (last subject last visit).
Pre-assignment details
A total of 63 subjects were screened and 54 subjects were randomized into the aflibercept group (N=27) and the sham group (N =27).
Participants by arm
| Arm | Count |
|---|---|
| Aflibercept 2 mg Intravitreal (IVT) Injection Group Subjects received intravitreal (IVT) injection of 2 mg (0.05 milliliter \[ml\] \* 40 milligram per milliliter \[mg/ml\]) aflibercept on Day 1. Then, subjects may receive sham injection at Week 1, and aflibercept injection at Week 5 and/or Week 9 if the re-treatment criteria are met. Re-treatment criteria (subjects could receive aflibercept IVT injection when all the following retreatment criteria were met) :
* IOP higher than 21mmHg;
* Incomplete regression of iris neovascularization and;
* Aflibercept IVT deemed necessary by the investigator. | 27 |
| Sham Injection Group Subjects received a sham injection on Day 1. Then, subjects may receive aflibercept injection at Week 1, Week 5 and/or Week 9 if the re-treatment criteria specified in the protocol are met. Re-treatment criteria (subjects could receive aflibercept IVT injection when all the following retreatment criteria were met) :
* IOP higher than 21mmHg;
* Incomplete regression of iris neovascularization and;
* Aflibercept IVT deemed necessary by the investigator. | 27 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Progressive disease | 6 | 3 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Treatment unblinded | 0 | 1 |
Baseline characteristics
| Characteristic | Aflibercept 2 mg Intravitreal (IVT) Injection Group | Sham Injection Group | Total |
|---|---|---|---|
| Age, Continuous | 68.1 Years STANDARD_DEVIATION 12.7 | 66.2 Years STANDARD_DEVIATION 13.7 | 67.1 Years STANDARD_DEVIATION 13.1 |
| Sex: Female, Male Female | 5 Participants | 4 Participants | 9 Participants |
| Sex: Female, Male Male | 22 Participants | 23 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 10 / 27 | 12 / 27 | 6 / 27 | 7 / 27 |
| serious Total, serious adverse events | 3 / 27 | 3 / 27 | 0 / 27 | 0 / 27 |
Outcome results
Primary
Change in Intraocular Pressure (IOP) From Baseline to Pre-dose at Week 1
It compared the change in IOP from baseline to pre-dose at Week 1 between the aflibercept group vs the sham group.
Time frame: From baseline to pre-dose at Week 1
Population: FAS: The Full Analysis Set (FAS) included all randomized subjects who have received any study drug (including sham injection) and had had a baseline and at least one post-baseline IOP measurement on a posterior date. The FAS was analyzed as randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept 2 mg Intravitreal (IVT) Injection Group | Change in Intraocular Pressure (IOP) From Baseline to Pre-dose at Week 1 | -8.5 mmHg | Standard Deviation 8.7 |
| Sham Injection Group | Change in Intraocular Pressure (IOP) From Baseline to Pre-dose at Week 1 | -4.9 mmHg | Standard Deviation 10.8 |
Comparison: Point estimate, 95% CI and P-value were based on treatment difference of the LS mean changes using an ANCOVA model with treatment group and stage of NVG for randomization as fixed effects, baseline value as covariate. The superiority of aflibercept injection to sham injection was to be established if the upper limit of the two-sided 95% confidence interval for the difference (the aflibercept group minus the sham group) is less than 0.p-value: 0.064495% CI: [-10.2, 0.3]ANCOVA
Secondary
Percentage of Subjects Who Had Improved Neovascularization of the Iris (NVI) Grade From Baseline to Pre-dose at Week 1
NVI were assessed in the study eye using the NVI grading systems (grade 0 to grade 4). A subject who shows the improvement by at least one grade is considered to be improved. Percentage of subjects who had improved NVI grade was reported.
Time frame: From baseline to pre-dose at Week 1
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aflibercept 2 mg Intravitreal (IVT) Injection Group | Percentage of Subjects Who Had Improved Neovascularization of the Iris (NVI) Grade From Baseline to Pre-dose at Week 1 | 70.4 Percentage of participants |
| Sham Injection Group | Percentage of Subjects Who Had Improved Neovascularization of the Iris (NVI) Grade From Baseline to Pre-dose at Week 1 | 11.5 Percentage of participants |
Comparison: The point estimate of the treatment difference (the aflibercept group minus the sham group) at Week 1 and its two-sided 95% confidence interval stratified by stage of NVG (as randomized) using Mantel-Haenszel weights.95% CI: [37, 81.2]Mantel Haenszel