Age-Related Macular Degeneration, Choroid Neovascularization
Conditions
Brief summary
This is a 24-month study to evaluate multiple doses of AGN211745 (previously known as Sirna-027) in treatment of subfoveal choroidal neovascularization associated with age-related macular degeneration
Interventions
DRUGAGN 211745
AGN 211745 Solution 1000µg injection at Day 1, Month 1, Month 2
DRUGRanibizumab 500µg
Ranibizumab 500µg injections at Day 1, Month 1, Month 2
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 50 years or older with wet AMD as determined by an ophthalmologist * decrease in visual acuity (20/40 to 20/640) in at least one eye
Exclusion criteria
* Uncontrolled systemic disease * History of heart attack or stroke within one year of study entry * Symptomatic coronary artery disease * Cataracts that interfere with vision
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Improvement in Best Corrected Visual Acuity (BCVA) of 15 or More Letters at Month 3 | Month 3 | Percentage of patients with improvement in BCVA of 15 or more letters at Month 3. BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters). The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Lesion Size as Assessed by Fluorescein Angiography (FA) and Photography at Month 3 | Month 3 | Lesion size as assessed by FA and photography at month 3. FA is a technique for examining the circulation of the retina (and detecting any leakage) using a dye-tracing method. Photographs are taken with a specialized low-power microscope with an attached camera designed to photograph the interior of the eye, including the retina and optic disc. |
| Foveal Thickness as Assessed by Optical Coherence Tomography (OCT) at Month 3 | Month 3 | Foveal thickness as assessed by OCT at month 3. The fovea is a part of the eye, located in the center of the macula region of the retina. OCT is a laser-based, noninvasive, diagnostic system providing high-resolution, three-dimensional images of the retina. The fovea is responsible for sharp central vision, which is necessary for reading or any activity where visual detail is of primary importance. Normal foveal thickness ranges from 175 to 250 microns. A foveal thickness greater than 250 microns represents worsening vision. |
| Visual Functioning Questionnaire (VFQ) at Month 3 | Month 3 | Visual Functioning Questionnaire (VFQ) at Month 3. The VFQ includes 25 questions which assess visual impairment on functioning and specific aspects of health-related quality of life. Study terminated; data for this outcome measure were not analyzed. |
| Time to Treatment With Standard of Care at Month 6 | Month 6 | Time to treatment with standard-of-care at month 6, defined as the number of days before the use of rescue therapy occurred. |
Countries
Australia, Philippines, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AGN 211745 Solution 1000 ug AGN 211745 Solution 1000 ug | 34 |
| AGN 211745 Solution 300 ug AGN 211745 Solution 300 ug | 35 |
| AGN 211745 Solution 100 ug AGN 211745 Solution 100 ug | 35 |
| Ranibizumab 500 ug Ranibizumab 500 ug | 34 |
| Total | 138 |
Baseline characteristics
| Characteristic | Total | AGN 211745 Solution 1000 ug | AGN 211745 Solution 300 ug | AGN 211745 Solution 100 ug | Ranibizumab 500 ug |
|---|---|---|---|---|---|
| Age, Customized >=65 years | 122 participants | 32 participants | 30 participants | 30 participants | 30 participants |
| Age, Customized Between 45 and 65 years | 16 participants | 2 participants | 5 participants | 5 participants | 4 participants |
| Sex: Female, Male Female | 76 Participants | 19 Participants | 19 Participants | 24 Participants | 14 Participants |
| Sex: Female, Male Male | 62 Participants | 15 Participants | 16 Participants | 11 Participants | 20 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 | 29 / 34 | 26 / 35 | 28 / 35 | 24 / 34 |
| serious Total, serious adverse events | 4 / 34 | 3 / 35 | 3 / 35 | 9 / 34 |
Outcome results
Primary
Percentage of Patients With Improvement in Best Corrected Visual Acuity (BCVA) of 15 or More Letters at Month 3
Percentage of patients with improvement in BCVA of 15 or more letters at Month 3. BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters). The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved.
Time frame: Month 3
Population: Intent-To-Treat (ITT). The ITT population included all patients who started the study (randomized).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AGN 211745 Solution 1000 ug | Percentage of Patients With Improvement in Best Corrected Visual Acuity (BCVA) of 15 or More Letters at Month 3 | 5.9 Percentage of Patients |
| AGN 211745 Solution 300 ug | Percentage of Patients With Improvement in Best Corrected Visual Acuity (BCVA) of 15 or More Letters at Month 3 | 2.9 Percentage of Patients |
| AGN 211745 Solution 100 ug | Percentage of Patients With Improvement in Best Corrected Visual Acuity (BCVA) of 15 or More Letters at Month 3 | 0 Percentage of Patients |
| Ranibizumab 500 ug | Percentage of Patients With Improvement in Best Corrected Visual Acuity (BCVA) of 15 or More Letters at Month 3 | 17.6 Percentage of Patients |
Secondary
Foveal Thickness as Assessed by Optical Coherence Tomography (OCT) at Month 3
Foveal thickness as assessed by OCT at month 3. The fovea is a part of the eye, located in the center of the macula region of the retina. OCT is a laser-based, noninvasive, diagnostic system providing high-resolution, three-dimensional images of the retina. The fovea is responsible for sharp central vision, which is necessary for reading or any activity where visual detail is of primary importance. Normal foveal thickness ranges from 175 to 250 microns. A foveal thickness greater than 250 microns represents worsening vision.
Time frame: Month 3
Population: Intent-To-Treat (ITT). The ITT population included all patients who started the study (randomized).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AGN 211745 Solution 1000 ug | Foveal Thickness as Assessed by Optical Coherence Tomography (OCT) at Month 3 | 484.6 Microns | Standard Deviation 142.21 |
| AGN 211745 Solution 300 ug | Foveal Thickness as Assessed by Optical Coherence Tomography (OCT) at Month 3 | 413.2 Microns | Standard Deviation 103.59 |
| AGN 211745 Solution 100 ug | Foveal Thickness as Assessed by Optical Coherence Tomography (OCT) at Month 3 | 437.1 Microns | Standard Deviation 125.46 |
| Ranibizumab 500 ug | Foveal Thickness as Assessed by Optical Coherence Tomography (OCT) at Month 3 | 269.8 Microns | Standard Deviation 76.72 |
Secondary
Lesion Size as Assessed by Fluorescein Angiography (FA) and Photography at Month 3
Lesion size as assessed by FA and photography at month 3. FA is a technique for examining the circulation of the retina (and detecting any leakage) using a dye-tracing method. Photographs are taken with a specialized low-power microscope with an attached camera designed to photograph the interior of the eye, including the retina and optic disc.
Time frame: Month 3
Population: Intent-To-Treat. The ITT population included all patients who started the study (randomized).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AGN 211745 Solution 1000 ug | Lesion Size as Assessed by Fluorescein Angiography (FA) and Photography at Month 3 | 6.17 Millimeters squared (mm^2) | Standard Deviation 4.339 |
| AGN 211745 Solution 300 ug | Lesion Size as Assessed by Fluorescein Angiography (FA) and Photography at Month 3 | 4.29 Millimeters squared (mm^2) | Standard Deviation 3.264 |
| AGN 211745 Solution 100 ug | Lesion Size as Assessed by Fluorescein Angiography (FA) and Photography at Month 3 | 6.54 Millimeters squared (mm^2) | Standard Deviation 6.102 |
| Ranibizumab 500 ug | Lesion Size as Assessed by Fluorescein Angiography (FA) and Photography at Month 3 | 3.89 Millimeters squared (mm^2) | Standard Deviation 3.396 |
Secondary
Time to Treatment With Standard of Care at Month 6
Time to treatment with standard-of-care at month 6, defined as the number of days before the use of rescue therapy occurred.
Time frame: Month 6
Population: Intent-To-Treat (ITT). The ITT population included all patients who started the study (randomized).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AGN 211745 Solution 1000 ug | Time to Treatment With Standard of Care at Month 6 | 91.0 Number of Days |
| AGN 211745 Solution 300 ug | Time to Treatment With Standard of Care at Month 6 | 91.5 Number of Days |
| AGN 211745 Solution 100 ug | Time to Treatment With Standard of Care at Month 6 | 92.0 Number of Days |
| Ranibizumab 500 ug | Time to Treatment With Standard of Care at Month 6 | 130.5 Number of Days |
Secondary
Visual Functioning Questionnaire (VFQ) at Month 3
Visual Functioning Questionnaire (VFQ) at Month 3. The VFQ includes 25 questions which assess visual impairment on functioning and specific aspects of health-related quality of life. Study terminated; data for this outcome measure were not analyzed.
Time frame: Month 3
Population: Intent-To-Treat (ITT). The ITT population included all patients who started the study (randomized). Data for this outcome measure were not analyzed as the study was terminated early.