Age-Related Macular Degeneration
Conditions
Brief summary
The objectives of this study are to evaluate the safety and efficacy of E10030 intravitreous injection when administered in combination with Lucentis® against a control of Lucentis® alone in subjects with subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD).
Detailed description
Subjects will be randomized in a 1:1:1 ratio to the following dose groups: * E10030 0.3 mg/eye + Lucentis® 0. 5 mg/eye * E10030 1.5 mg/eye + Lucentis® 0. 5 mg/eye * E10030 sham + Lucentis® 0. 5 mg/eye Subjects will be treated with active E10030 or sham E10030 in combination with Lucentis® at Day 0, Week 4, Week 8, Week 12, Week 16 and Week 20. Primary Efficacy Endpoint: The primary efficacy endpoint is mean change in visual acuity from baseline at the Week 24 visit Safety Endpoints: Safety endpoints include adverse events, vital signs, ophthalmic variables \[visual acuity, intraocular pressure (IOP), ophthalmic examination, color fundus photography, fluorescein angiograms (FA), optical coherence tomography (OCT)\], and laboratory variables. Approximately 444 subjects will be randomized into one of the three treatment cohorts (approximately 148 patients per dose group).
Interventions
DRUGE10030 plus Lucentis
once a month intravitreal injection
DRUGLucentis
10 mg/mL intravitreal injection monthly
Sponsors
Ophthotech Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Subfoveal choroidal neovascularization (CNV) due to AMD
Exclusion criteria
Any of the following underlying diseases including: * Diabetes mellitus * History or evidence of severe cardiac disease (e.g., NYHA Functional Class III or IV - see Appendix 19.6), history or clinical evidence of unstable angina, acute coronary syndrome, myocardial infarction or coronary artery revascularization within 6 months, or ventricular tachyarrhythmias requiring ongoing treatment. * Clinically significant impaired renal or hepatic function. * Stroke (within 12 months of trial entry). * Any major surgical procedure within one month of trial entry. * Known serious allergies to the fluorescein dye used in angiography (mild allergy amenable to treatment is allowable), to the components of the ranibizumab (Lucentis) formulation, or to the components of the E10030 formulation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Visual Acuity From Baseline at the Week 24 Visit | 24 Weeks | The primary efficacy endpoint is the mean change in visual acuity from baseline at the Week 24 visit |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Subjects Gaining 15 or More ETDRS Letters From Baseline at the Week 24 Visit | 24 weeks | The proportion of subjects gaining 15 or more ETDRS letters from baseline at the Week 24 visit |
| Proportion of Patients With at Least 1 Adverse Event | 24 weeks | — |
Countries
United States
Participant flow
Recruitment details
This study enrolled 449 patients at approximately 69 centers in North America, South America, Europe and Israel.
Participants by arm
| Arm | Count |
|---|---|
| Lucentis Sham/Lucentis 0.5 mg | 148 |
| E10030 Low Dose Plus Lucentis E10030 0.3 mg/Lucentis 0.5 mg | 149 |
| E10030 High Dose Plus Lucentis E10030 1.5 mg/Lucentis 0.5 mg | 152 |
| Total | 449 |
Baseline characteristics
| Characteristic | Lucentis | E10030 Low Dose Plus Lucentis | E10030 High Dose Plus Lucentis | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 140 Participants | 139 Participants | 141 Participants | 420 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 10 Participants | 11 Participants | 29 Participants |
| Age, Continuous | 78.0 years STANDARD_DEVIATION 7.98 | 77.6 years STANDARD_DEVIATION 8.19 | 77.8 years STANDARD_DEVIATION 8.36 | 77.8 years STANDARD_DEVIATION 8.16 |
| Region of Enrollment Europe | 87 participants | 85 participants | 82 participants | 254 participants |
| Region of Enrollment Israel | 10 participants | 10 participants | 14 participants | 34 participants |
| Region of Enrollment South America | 4 participants | 3 participants | 3 participants | 10 participants |
| Region of Enrollment United States | 47 participants | 51 participants | 53 participants | 151 participants |
| Sex: Female, Male Female | 93 Participants | 90 Participants | 92 Participants | 275 Participants |
| Sex: Female, Male Male | 55 Participants | 59 Participants | 60 Participants | 174 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 63 / 148 | 63 / 149 | 69 / 152 |
| serious Total, serious adverse events | 12 / 148 | 14 / 149 | 10 / 152 |
Outcome results
Primary
Mean Change in Visual Acuity From Baseline at the Week 24 Visit
The primary efficacy endpoint is the mean change in visual acuity from baseline at the Week 24 visit
Time frame: 24 Weeks
Population: Intent to Treat Population (last observation carried forward)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lucentis | Mean Change in Visual Acuity From Baseline at the Week 24 Visit | 6.5 ETDRS Letters | Standard Error 1.09 |
| E10030 0.3 mg/Lucentis 0.5 mg | Mean Change in Visual Acuity From Baseline at the Week 24 Visit | 8.8 ETDRS Letters | Standard Error 1.09 |
| E10030 1.5 mg/Lucentis 0.5 mg | Mean Change in Visual Acuity From Baseline at the Week 24 Visit | 10.6 ETDRS Letters | Standard Error 1.07 |
Secondary
Proportion of Patients With at Least 1 Adverse Event
Time frame: 24 weeks
Population: Safety Analysis Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lucentis | Proportion of Patients With at Least 1 Adverse Event | 65.5 % of patients with adverse events |
| E10030 0.3 mg/Lucentis 0.5 mg | Proportion of Patients With at Least 1 Adverse Event | 67.1 % of patients with adverse events |
| E10030 1.5 mg/Lucentis 0.5 mg | Proportion of Patients With at Least 1 Adverse Event | 65.1 % of patients with adverse events |
Secondary
The Proportion of Subjects Gaining 15 or More ETDRS Letters From Baseline at the Week 24 Visit
The proportion of subjects gaining 15 or more ETDRS letters from baseline at the Week 24 visit
Time frame: 24 weeks
Population: Intent to Treat Population (last observation carried forward)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lucentis | The Proportion of Subjects Gaining 15 or More ETDRS Letters From Baseline at the Week 24 Visit | 34.0 % subjects (i.e gaining >/=15 letters) |
| E10030 0.3 mg/Lucentis 0.5 mg | The Proportion of Subjects Gaining 15 or More ETDRS Letters From Baseline at the Week 24 Visit | 33.3 % subjects (i.e gaining >/=15 letters) |
| E10030 1.5 mg/Lucentis 0.5 mg | The Proportion of Subjects Gaining 15 or More ETDRS Letters From Baseline at the Week 24 Visit | 39.1 % subjects (i.e gaining >/=15 letters) |