Exudative Age-Related Macular Degeneration
Conditions
Keywords
Wet AMD, Intravitreal Injection, Macular Degeneration, VEGF treatment
Brief summary
The primary purpose of this study was to demonstrate a biological effect of AL-78898A, as measured by change (reduction) in central subfield (CSF) retinal thickness 4 weeks after a single intravitreal injection, as compared to LUCENTIS.
Detailed description
The study consisted of a Screening Visit (Visit 1), a Day 0 visit (Visit 2), 6 on-therapy visits at Day 1, Weeks 1, 2, 3, 4, and 8 (Visits 3-8), and an Exit Visit at Week 12 (Visit 9). Patients who met all inclusion and exclusion criteria at Visit 1 were randomized in a 3:1 ratio to receive either AL-78898A or LUCENTIS as a single 50-μL injection in the study eye. Additionally, patients received standard therapy for exudative AMD beginning at Week 2/Visit 5 if the patient was not improving per protocol-specified criteria. Beginning at Week 4/Visit 7, patients not improving received standard therapy for exudative AMD at the investigator's discretion.
Interventions
DRUGAL-78898A
Investigational treatment
DRUGRanibizumab
Anti-vascular endothelial growth factor (VEGF) treatment
Sponsors
Alcon Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Willing to give informed consent, make the required study visits and follow instructions; * Newly diagnosed with exudative age-related macular degeneration (AMD); * Presence of primary juxta- or subfoveal choroidal neovascularization (CNV) secondary to AMD (study eye); * Best-corrected visual acuity (BCVA) in study eye as specified in protocol; * No vision-threatening ocular condition other than AMD, in the opinion of the Investigator; * Other protocol-specified inclusion criteria may apply.
Exclusion criteria
* History or current evidence of macular or retinal disease other than exudative AMD (study eye); * Any evidence of fibrosis or scarring within the CNV (choroidal neovascularization)lesion (study eye); * Any evidence of vitreous hemorrhage (study eye); * History or evidence of surgery (study eye), as specified in protocol; * Any active systemic infection or ocular/intraocular infection or inflammation in either eye; * A history or current medical diagnosis of glaucoma or ocular hypertension (study eye), as specified in protocol; * History or current evidence of a medical condition that may in the opinion of the Investigator preclude the safe administration of test article, adherence to the scheduled study visits, safe participation in the study or affect the results of the study * History of severe or serious hypersensitivity to any component of the investigational product, reference product or clinically relevant sensitivity to fluorescein dye, as assessed by the Investigator; * Females of childbearing potential may not participate in the study if pregnant, lactating, or not using adequate birth control methods for the duration of the study; * Participation in any ocular or non-ocular investigational study within 30 days of screening; * Has received any approved or investigational therapy for AMD in the study eye with the exception of vitamins; * Other protocol-defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Reduction From Baseline in Central Subfield (CSF) Retinal Thickness at Week 4 | Week 4 | The thickness of the retina was measured using a non-invasive device that produces cross-sectional and 3D images of the eye. The reduction was calculated by subtracting Week 4 visit value from the Baseline value. A positive number indicates a reduction in thickness compared to baseline, whereas a negative number indicates an increase in thickness. An increase in thickness as compared to baseline may indicate a progression of the underlying disease. |
| Incidence of Events of Special Interest (ESI) | Up to Day 30 | An ESI was a protocol-specified event of scientific and medical concern specific to the Sponsor's product or program where ongoing monitoring and rapid communication by the Investigator to the Sponsor was appropriate. These adverse events could have been serious or nonserious and may have required further investigation in order to characterize and understand. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from 14 study centers in the US.
Pre-assignment details
Of the 99 subjects enrolled, 48 were considered screen failures and were exited from the study prior to randomization. Of the 51 subjects randomized, 2 did not receive treatment. This reporting group includes all randomized subjects who received study medication.
Participants by arm
| Arm | Count |
|---|---|
| AL-78898A Single 50-µL (microliter) intravitreal injection with 12 weeks follow-up | 38 |
| Lucentis Single 50-µL (microliter) intravitreal injection with 12 weeks follow-up | 11 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
Baseline characteristics
| Characteristic | AL-78898A | Lucentis | Total |
|---|---|---|---|
| Age, Customized 18 to 64 years | 3 participants | 0 participants | 3 participants |
| Age, Customized ≥65 years | 35 participants | 11 participants | 46 participants |
| Region of Enrollment United States | 38 participants | 11 participants | 49 participants |
| Sex: Female, Male Female | 21 Participants | 4 Participants | 25 Participants |
| Sex: Female, Male Male | 17 Participants | 7 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 14 / 38 | 5 / 11 |
| serious Total, serious adverse events | 5 / 38 | 1 / 11 |
Outcome results
Primary
Incidence of Events of Special Interest (ESI)
An ESI was a protocol-specified event of scientific and medical concern specific to the Sponsor's product or program where ongoing monitoring and rapid communication by the Investigator to the Sponsor was appropriate. These adverse events could have been serious or nonserious and may have required further investigation in order to characterize and understand.
Time frame: Up to Day 30
Population: Intent-to-treat (ITT): All patients who received study medication and completed at least one scheduled post-injection study visit
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AL-78898A | Incidence of Events of Special Interest (ESI) | 2 events |
| Lucentis | Incidence of Events of Special Interest (ESI) | 0 events |
Primary
Mean Reduction From Baseline in Central Subfield (CSF) Retinal Thickness at Week 4
The thickness of the retina was measured using a non-invasive device that produces cross-sectional and 3D images of the eye. The reduction was calculated by subtracting Week 4 visit value from the Baseline value. A positive number indicates a reduction in thickness compared to baseline, whereas a negative number indicates an increase in thickness. An increase in thickness as compared to baseline may indicate a progression of the underlying disease.
Time frame: Week 4
Population: All patients who received study medication, completed at least one scheduled post-injection study visit, and did not receive standard therapy prior to Week 4 assessment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AL-78898A | Mean Reduction From Baseline in Central Subfield (CSF) Retinal Thickness at Week 4 | Baseline | 514.2 microns | Standard Deviation 158 |
| AL-78898A | Mean Reduction From Baseline in Central Subfield (CSF) Retinal Thickness at Week 4 | Week 4 | -12.1 microns | Standard Deviation 87.2 |
| Lucentis | Mean Reduction From Baseline in Central Subfield (CSF) Retinal Thickness at Week 4 | Baseline | 551.8 microns | Standard Deviation 119 |
| Lucentis | Mean Reduction From Baseline in Central Subfield (CSF) Retinal Thickness at Week 4 | Week 4 | 199.9 microns | Standard Deviation 139.6 |