Exudative Age-Related Macular Degeneration
Conditions
Keywords
LHA510, PoC, Age-related macular degeneration
Brief summary
The purpose of this study is to evaluate the efficacy of 84 successive days of topically administered LHA510 compared to vehicle in reducing the number of patients requiring intravitreal (IVT) anti-vascular endothelial growth factor (VEGF) therapy (Lucentis®) for recurrence of active choroidal neovascularization (CNV).
Detailed description
On Day -1, patients will receive an IVT Lucentis® injection in the study eye, and then will be randomized to receive either topical LHA510 ophthalmic suspension or vehicle in a 1:1 ratio for 84 days. Patients with recurrence of active CNV in the study eye during the study will receive rescue IVT Lucentis® injections. Following the treatment period, subjects will return for a follow-up visit and a disposition visit. Only one eye (designated as the study eye) will be dosed with either topical LHA510 or vehicle per patient.
Interventions
DRUGLHA510 vehicle
Inactive ingredients used as a placebo comparator
For intravitreal (IVT) injection
Sponsors
Alcon, a Novartis Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Sign written informed consent form; * Wet AMD; * IVT anti-VEGF therapy for at least 6 months and a maximum of 7 years since the 3rd loading dose; * BCVA 50 letters (approximate Snellen equivalent 20/100) or better in the study eye; * Demonstrate ability to administer eye drops (subject or care-giver); * CNV recently demonstrated high need for frequent anti-VEGF therapy and a sustained functional and clear anatomical response to the therapy in the study eye; * Other protocol-specified inclusion criteria may apply.
Exclusion criteria
* Any active ocular or periocular infection or intraocular inflammation; * Current or history of macular or retinal disease (if visually significant) other than wet AMD in the study eye; * Current clinically significant vitreous hemorrhage or history of rhegmatogenous retinal detachment affecting the macula in the study eye; * History of hypersensitivity to any of the study drugs or clinically relevant sensitivity to fluorescein dye or povidone iodine; * Women of child-bearing potential; * History of a medical condition that, in the opinion of the Investigator, would preclude scheduled study visits, completion of the study or a safe administration of investigational product; * Other protocol-specified
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Positive LUCENTIS® Retreatment Status at Day 84 | Day 84 | For subjects who completed the Day 84 visit, retreatment need status was positive if LUCENTIS® retreatment (injection) was required before or at Day 84, including requiring retreatment at or before the Day 84 visit with the actual retreatment performed at a later visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of LUCENTIS® Retreatment Needs Identified Required up to Day 84 | Up to Day 84 | The number of LUCENTIS retreatment needs identified before or at the Day 84 visit (even if retreatment was applied at a later visit) for each patient was used in the analysis |
| Number of Subjects Requiring LUCENTIS® Retreatment at Days 28 and 56 | Day 28, Day 56 | The number of LUCENTIS® retreatment needs identified before or at the Day 28 and Day 56 visits (even if retreatment was applied at a later visit) for each subject was used in the analysis. |
| Change From Randomization Visit (Day -1) in Central Subfield Thickness Total (CSFTtot) at All Visits at the Study Site | Day -1, Day 14, Day 28, Day 56, Day 84 | The thickness of the retina was measured using SD-OCT and reported as a difference, in micrometers, between a given post-Randomization Visit and Randomization Visit (Day-1). A negative number indicates a reduction in thickness, whereas a positive number indicates an increase. An increase in thickness may indicate a progression of the underlying disease. Only one eye (study eye) contributed to the analysis. |
| Change From Randomization Visit (Day -1) in Best Corrected Visual Acuity (BCVA) at All Visits at the Study Site | Day -1, Day 14, Day 28, Day 56, Day 84 | Measurement of best corrected (with spectacles or other visual corrective devices) visual acuity was conducted in each eye individually using ETDRS charts and reported in number of letters read correctly. An increase (gain) in letters read from the baseline assessment indicates improvement. Only one eye (study eye) contributed to the analysis. |
| Change From Randomization Visit (Day -1) in Central Subfield Thickness, Neuro-retina (CSFTnr) by Visit | Day -1, Day 28, Day 84 | The thickness of the neuro-retina, at the level of the central subfield, was measured using SD-OCT and reported as a difference, in micrometers, between a given post-Randomization Visit and Randomization Visit (Day-1). A negative number indicates a reduction in thickness, whereas a positive number indicates an increase. An increase in thickness may indicate a progression of the underlying disease. Only one eye (study eye) contributed to the analysis. |
| Time to First LUCENTIS® Retreatment Need Identification up to Day 84 | Day 14, Day 28, Day 56, Day 84 | The time was determined based on the visit of the treatment period when a patient was identified as requiring retreatment with LUCENTIS. |
| Change From Randomization Visit (Day -1) in Subretinal Fluid - Foveal Involvement (SRFfi) Thickness by Visit | Day -1, Day 28, Day 84 | The thickness of subretinal fluid involving the fovea was measured using SD-OCT and reported as a difference, in micrometers, between a given post-Randomization Visit and Randomization Visit (Day-1). A negative number indicates a reduction in thickness, whereas a positive number indicates an increase. An increase in thickness of subretinal fluid involving the fovea may indicate a progression of the underlying disease. Only one eye (study eye) contributed to the analysis. |
| Change From Randomization Visit (Day -1) in Pigment Epithelial Detachment - Foveal Involvement (PEDfi) Thickness by Visit | Day -1, Day 28, Day 84 | The thickness of pigment epithelial detachment involving the fovea was measured using SD-OCT and reported as a difference, in micrometers, between a given post-Randomization Visit and Randomization Visit (Day-1). A negative number indicates a reduction in thickness, whereas a positive number indicates an increase. An increase in thickness of pigment epithelial detachment involving the fovea may indicate a progression of the underlying disease. Only one eye (study eye) contributed to the analysis. |
| Change From Randomization Visit (Day -1) in Total Lesion Size by Visit | Day -1, Day 84 | The total wet AMD lesion size was measured using FA and reported as a difference, in millimeter squared, between a given post-Randomization Visit and Randomization Visit (Day-1). A negative number indicates a reduction, whereas a positive number indicates an increase. An increase in wet AMD lesion size may indicate a progression of the underlying disease. Only one eye (study eye) contributed to the analysis. |
| Change From Randomization Visit (Day -1) in CNV Size by Visit | Day -1, Day 84 | The size of CNV (area of new blood vessels in the choroid layer of the retina) was measured using FA and reported as a difference, in millimeter squared, between a given post-Randomization Visit and Randomization Visit (Day-1). A negative number indicates a reduction, whereas a positive number indicates an increase. An increase in CNV size may indicate a progression of the underlying disease. Only one eye (study eye) contributed to the analysis. |
| Plasma Concentration of LHA510 and CRA398 | Day 28, Day 84 | Samples collected from subjects, after multiple topical ocular dosing of LHA510, were analyzed to determine concentrations of LHA510 and its metabolite, CRA398. Plasma LHA510 and CRA398 concentrations were quantitated by a validated liquid chromatography-tandem mass spectroscopy assay method. Below the limit of quantification (BLQ) is treated as zero. |
| Change From Randomization Visit (Day -1) in Lesion Thickness by Visit | Day -1, Day 28, Day 84 | The thickness of the neovascular lesion was measured using SD-OCT and reported as a difference, in micrometers, between a given post-Randomization Visit and Randomization Visit (Day-1). A negative number indicates a reduction in thickness, whereas a positive number indicates an increase. An increase in thickness of the neovascular lesion may indicate a progression of the underlying disease. Only one eye (study eye) contributed to the analysis. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from 20 study centers located in the United States.
Pre-assignment details
Of the 136 enrolled, 37 subjects were exited as screen failures and another 6 subjects were discontinued prior to randomization. This reporting group includes all randomized subjects (93).
Participants by arm
| Arm | Count |
|---|---|
| LHA510 LHA510 ophthalmic suspension administered topically in the study eye as specified in the protocol for 84 days, with ranibizumab ophthalmic solution for IVT injection as standard of care rescue therapy. | 46 |
| Vehicle LHA510 vehicle administered topically in the study eye as specified in the protocol for 84 days, with ranibizumab ophthalmic solution for IVT injection as standard of care rescue therapy. | 45 |
| Total | 91 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Deemed ineligible after randomization | 8 | 4 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Vehicle | Total | LHA510 |
|---|---|---|---|
| Age, Continuous | 76.8 years STANDARD_DEVIATION 7.94 | 77.1 years STANDARD_DEVIATION 7.8 | 77.3 years STANDARD_DEVIATION 7.74 |
| Best-corrected visual acuity (BCVA) | 70.5 letters STANDARD_DEVIATION 8.87 | 70.9 letters STANDARD_DEVIATION 9.09 | 71.2 letters STANDARD_DEVIATION 9.45 |
| Central Subfield Thickness Neuro-Retina (CSFTnr) | 239.0 μm STANDARD_DEVIATION 75.87 | 240.5 μm STANDARD_DEVIATION 64.17 | 242.2 μm STANDARD_DEVIATION 48.95 |
| Central Subfield Thickness Total (CSFTtot) | 374.9 μm STANDARD_DEVIATION 116.98 | 363.4 μm STANDARD_DEVIATION 112.29 | 350.5 μm STANDARD_DEVIATION 107.09 |
| Choroidal Neovascularization (CNV) Size | 7.7 mm^2 STANDARD_DEVIATION 5.72 | 6.9 mm^2 STANDARD_DEVIATION 5.33 | 6.0 mm^2 STANDARD_DEVIATION 4.79 |
| Lesion Thickness | 45.8 μm STANDARD_DEVIATION 92.83 | 33.8 μm STANDARD_DEVIATION 72.99 | 20.3 μm STANDARD_DEVIATION 37.9 |
| Pigment Epithelial Detachment - Foveal Involvement (PEDfi) Thickness | 82.6 μm STANDARD_DEVIATION 100.07 | 72.4 μm STANDARD_DEVIATION 96.39 | 60.9 μm STANDARD_DEVIATION 92.26 |
| Sex: Female, Male Female | 28 Participants | 50 Participants | 22 Participants |
| Sex: Female, Male Male | 17 Participants | 41 Participants | 24 Participants |
| Subretinal Fluid-Foveal Involvement (SRFfi) Thickness | 25.0 μm STANDARD_DEVIATION 50.76 | 32.4 μm STANDARD_DEVIATION 54.87 | 40.7 μm STANDARD_DEVIATION 58.81 |
| Total Lesion Size | 7.8 mm^2 STANDARD_DEVIATION 5.74 | 7.0 mm^2 STANDARD_DEVIATION 5.31 | 6.1 mm^2 STANDARD_DEVIATION 4.73 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 136 | 0 / 46 | 0 / 45 | 0 / 46 | 0 / 45 |
| other Total, other adverse events | 1 / 136 | 28 / 46 | 5 / 45 | 3 / 46 | 0 / 45 |
| serious Total, serious adverse events | 0 / 136 | 1 / 46 | 0 / 45 | 1 / 46 | 0 / 45 |
Outcome results
Primary
Number of Subjects With Positive LUCENTIS® Retreatment Status at Day 84
For subjects who completed the Day 84 visit, retreatment need status was positive if LUCENTIS® retreatment (injection) was required before or at Day 84, including requiring retreatment at or before the Day 84 visit with the actual retreatment performed at a later visit.
Time frame: Day 84
Population: Extended PPS-A4
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LHA510 | Number of Subjects With Positive LUCENTIS® Retreatment Status at Day 84 | 25 Participants |
| Vehicle | Number of Subjects With Positive LUCENTIS® Retreatment Status at Day 84 | 25 Participants |
Secondary
Change From Randomization Visit (Day -1) in Best Corrected Visual Acuity (BCVA) at All Visits at the Study Site
Measurement of best corrected (with spectacles or other visual corrective devices) visual acuity was conducted in each eye individually using ETDRS charts and reported in number of letters read correctly. An increase (gain) in letters read from the baseline assessment indicates improvement. Only one eye (study eye) contributed to the analysis.
Time frame: Day -1, Day 14, Day 28, Day 56, Day 84
Population: Extended PPS-A4. Missing Data Imputed Using LOCF.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LHA510 | Change From Randomization Visit (Day -1) in Best Corrected Visual Acuity (BCVA) at All Visits at the Study Site | Day 14 | 1.3 letters | Standard Error 0.8 |
| LHA510 | Change From Randomization Visit (Day -1) in Best Corrected Visual Acuity (BCVA) at All Visits at the Study Site | Day 28 | 1.7 letters | Standard Error 0.89 |
| LHA510 | Change From Randomization Visit (Day -1) in Best Corrected Visual Acuity (BCVA) at All Visits at the Study Site | Day 56 | -0.5 letters | Standard Error 1.28 |
| LHA510 | Change From Randomization Visit (Day -1) in Best Corrected Visual Acuity (BCVA) at All Visits at the Study Site | Day 84 | -1.7 letters | Standard Error 1.59 |
| Vehicle | Change From Randomization Visit (Day -1) in Best Corrected Visual Acuity (BCVA) at All Visits at the Study Site | Day 84 | 2.2 letters | Standard Error 1.5 |
| Vehicle | Change From Randomization Visit (Day -1) in Best Corrected Visual Acuity (BCVA) at All Visits at the Study Site | Day 14 | 1.6 letters | Standard Error 0.75 |
| Vehicle | Change From Randomization Visit (Day -1) in Best Corrected Visual Acuity (BCVA) at All Visits at the Study Site | Day 56 | 2.3 letters | Standard Error 1.21 |
| Vehicle | Change From Randomization Visit (Day -1) in Best Corrected Visual Acuity (BCVA) at All Visits at the Study Site | Day 28 | 2.5 letters | Standard Error 0.84 |
Secondary
Change From Randomization Visit (Day -1) in Central Subfield Thickness, Neuro-retina (CSFTnr) by Visit
The thickness of the neuro-retina, at the level of the central subfield, was measured using SD-OCT and reported as a difference, in micrometers, between a given post-Randomization Visit and Randomization Visit (Day-1). A negative number indicates a reduction in thickness, whereas a positive number indicates an increase. An increase in thickness may indicate a progression of the underlying disease. Only one eye (study eye) contributed to the analysis.
Time frame: Day -1, Day 28, Day 84
Population: Extended PPS-A4. Missing data imputed using LOCF.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LHA510 | Change From Randomization Visit (Day -1) in Central Subfield Thickness, Neuro-retina (CSFTnr) by Visit | Day 28 | -16.6 μm | Standard Deviation 22.62 |
| LHA510 | Change From Randomization Visit (Day -1) in Central Subfield Thickness, Neuro-retina (CSFTnr) by Visit | Day 84 | -4.1 μm | Standard Deviation 35.34 |
| Vehicle | Change From Randomization Visit (Day -1) in Central Subfield Thickness, Neuro-retina (CSFTnr) by Visit | Day 28 | -15.1 μm | Standard Deviation 38.21 |
| Vehicle | Change From Randomization Visit (Day -1) in Central Subfield Thickness, Neuro-retina (CSFTnr) by Visit | Day 84 | -8.8 μm | Standard Deviation 36.75 |
Secondary
Change From Randomization Visit (Day -1) in Central Subfield Thickness Total (CSFTtot) at All Visits at the Study Site
The thickness of the retina was measured using SD-OCT and reported as a difference, in micrometers, between a given post-Randomization Visit and Randomization Visit (Day-1). A negative number indicates a reduction in thickness, whereas a positive number indicates an increase. An increase in thickness may indicate a progression of the underlying disease. Only one eye (study eye) contributed to the analysis.
Time frame: Day -1, Day 14, Day 28, Day 56, Day 84
Population: Extended PPS-A4. Missing data imputed using the Last Observation Carried Forward (LOCF) approach.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LHA510 | Change From Randomization Visit (Day -1) in Central Subfield Thickness Total (CSFTtot) at All Visits at the Study Site | Day 14 | -46.9 μm | Standard Error 8.4 |
| LHA510 | Change From Randomization Visit (Day -1) in Central Subfield Thickness Total (CSFTtot) at All Visits at the Study Site | Day 28 | -38.6 μm | Standard Error 7.42 |
| LHA510 | Change From Randomization Visit (Day -1) in Central Subfield Thickness Total (CSFTtot) at All Visits at the Study Site | Day 56 | 11.3 μm | Standard Error 10.01 |
| LHA510 | Change From Randomization Visit (Day -1) in Central Subfield Thickness Total (CSFTtot) at All Visits at the Study Site | Day 84 | -16.8 μm | Standard Error 8.92 |
| Vehicle | Change From Randomization Visit (Day -1) in Central Subfield Thickness Total (CSFTtot) at All Visits at the Study Site | Day 84 | -12.2 μm | Standard Error 8.42 |
| Vehicle | Change From Randomization Visit (Day -1) in Central Subfield Thickness Total (CSFTtot) at All Visits at the Study Site | Day 14 | -43.0 μm | Standard Error 7.93 |
| Vehicle | Change From Randomization Visit (Day -1) in Central Subfield Thickness Total (CSFTtot) at All Visits at the Study Site | Day 56 | 1.0 μm | Standard Error 9.45 |
| Vehicle | Change From Randomization Visit (Day -1) in Central Subfield Thickness Total (CSFTtot) at All Visits at the Study Site | Day 28 | -28.9 μm | Standard Error 7 |
Secondary
Change From Randomization Visit (Day -1) in CNV Size by Visit
The size of CNV (area of new blood vessels in the choroid layer of the retina) was measured using FA and reported as a difference, in millimeter squared, between a given post-Randomization Visit and Randomization Visit (Day-1). A negative number indicates a reduction, whereas a positive number indicates an increase. An increase in CNV size may indicate a progression of the underlying disease. Only one eye (study eye) contributed to the analysis.
Time frame: Day -1, Day 84
Population: Extended PPS-A4 as observed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LHA510 | Change From Randomization Visit (Day -1) in CNV Size by Visit | -0.6 mm^2 | Standard Deviation 2 |
| Vehicle | Change From Randomization Visit (Day -1) in CNV Size by Visit | 0.5 mm^2 | Standard Deviation 1.71 |
Secondary
Change From Randomization Visit (Day -1) in Lesion Thickness by Visit
The thickness of the neovascular lesion was measured using SD-OCT and reported as a difference, in micrometers, between a given post-Randomization Visit and Randomization Visit (Day-1). A negative number indicates a reduction in thickness, whereas a positive number indicates an increase. An increase in thickness of the neovascular lesion may indicate a progression of the underlying disease. Only one eye (study eye) contributed to the analysis.
Time frame: Day -1, Day 28, Day 84
Population: Extended PPS-A4. Missing data imputed using LOCF.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LHA510 | Change From Randomization Visit (Day -1) in Lesion Thickness by Visit | Day 28 | -1.9 μm | Standard Deviation 38.05 |
| LHA510 | Change From Randomization Visit (Day -1) in Lesion Thickness by Visit | Day 84 | 1.4 μm | Standard Deviation 26.46 |
| Vehicle | Change From Randomization Visit (Day -1) in Lesion Thickness by Visit | Day 28 | 6.9 μm | Standard Deviation 43.66 |
| Vehicle | Change From Randomization Visit (Day -1) in Lesion Thickness by Visit | Day 84 | 6.9 μm | Standard Deviation 43.96 |
Secondary
Change From Randomization Visit (Day -1) in Pigment Epithelial Detachment - Foveal Involvement (PEDfi) Thickness by Visit
The thickness of pigment epithelial detachment involving the fovea was measured using SD-OCT and reported as a difference, in micrometers, between a given post-Randomization Visit and Randomization Visit (Day-1). A negative number indicates a reduction in thickness, whereas a positive number indicates an increase. An increase in thickness of pigment epithelial detachment involving the fovea may indicate a progression of the underlying disease. Only one eye (study eye) contributed to the analysis.
Time frame: Day -1, Day 28, Day 84
Population: Extended PPS-A4. Missing Data Imputed Using LOCF.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LHA510 | Change From Randomization Visit (Day -1) in Pigment Epithelial Detachment - Foveal Involvement (PEDfi) Thickness by Visit | Day 28 | -0.3 μm | Standard Deviation 38.92 |
| LHA510 | Change From Randomization Visit (Day -1) in Pigment Epithelial Detachment - Foveal Involvement (PEDfi) Thickness by Visit | Day 84 | -0.2 μm | Standard Deviation 33.33 |
| Vehicle | Change From Randomization Visit (Day -1) in Pigment Epithelial Detachment - Foveal Involvement (PEDfi) Thickness by Visit | Day 28 | -13.3 μm | Standard Deviation 43.23 |
| Vehicle | Change From Randomization Visit (Day -1) in Pigment Epithelial Detachment - Foveal Involvement (PEDfi) Thickness by Visit | Day 84 | -7.6 μm | Standard Deviation 47.25 |
Secondary
Change From Randomization Visit (Day -1) in Subretinal Fluid - Foveal Involvement (SRFfi) Thickness by Visit
The thickness of subretinal fluid involving the fovea was measured using SD-OCT and reported as a difference, in micrometers, between a given post-Randomization Visit and Randomization Visit (Day-1). A negative number indicates a reduction in thickness, whereas a positive number indicates an increase. An increase in thickness of subretinal fluid involving the fovea may indicate a progression of the underlying disease. Only one eye (study eye) contributed to the analysis.
Time frame: Day -1, Day 28, Day 84
Population: Extended PPS-A4. Missing Data Imputed Using LOCF.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LHA510 | Change From Randomization Visit (Day -1) in Subretinal Fluid - Foveal Involvement (SRFfi) Thickness by Visit | Day 28 | -18.5 μm | Standard Deviation 44.67 |
| LHA510 | Change From Randomization Visit (Day -1) in Subretinal Fluid - Foveal Involvement (SRFfi) Thickness by Visit | Day 84 | -14.1 μm | Standard Deviation 54.08 |
| Vehicle | Change From Randomization Visit (Day -1) in Subretinal Fluid - Foveal Involvement (SRFfi) Thickness by Visit | Day 28 | -11.0 μm | Standard Deviation 34.73 |
| Vehicle | Change From Randomization Visit (Day -1) in Subretinal Fluid - Foveal Involvement (SRFfi) Thickness by Visit | Day 84 | -5.9 μm | Standard Deviation 31.33 |
Secondary
Change From Randomization Visit (Day -1) in Total Lesion Size by Visit
The total wet AMD lesion size was measured using FA and reported as a difference, in millimeter squared, between a given post-Randomization Visit and Randomization Visit (Day-1). A negative number indicates a reduction, whereas a positive number indicates an increase. An increase in wet AMD lesion size may indicate a progression of the underlying disease. Only one eye (study eye) contributed to the analysis.
Time frame: Day -1, Day 84
Population: Extended PPS-A4 as observed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LHA510 | Change From Randomization Visit (Day -1) in Total Lesion Size by Visit | -0.3 mm^2 | Standard Deviation 1.71 |
| Vehicle | Change From Randomization Visit (Day -1) in Total Lesion Size by Visit | 0.5 mm^2 | Standard Deviation 1.81 |
Secondary
Number of LUCENTIS® Retreatment Needs Identified Required up to Day 84
The number of LUCENTIS retreatment needs identified before or at the Day 84 visit (even if retreatment was applied at a later visit) for each patient was used in the analysis
Time frame: Up to Day 84
Population: Extended PPS-A4
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LHA510 | Number of LUCENTIS® Retreatment Needs Identified Required up to Day 84 | 0 retreatment injections | 8 participants |
| LHA510 | Number of LUCENTIS® Retreatment Needs Identified Required up to Day 84 | 1 retreatment injection | 18 participants |
| LHA510 | Number of LUCENTIS® Retreatment Needs Identified Required up to Day 84 | 2 retreatment injections | 6 participants |
| LHA510 | Number of LUCENTIS® Retreatment Needs Identified Required up to Day 84 | 3 retreatment injections | 1 participants |
| Vehicle | Number of LUCENTIS® Retreatment Needs Identified Required up to Day 84 | 3 retreatment injections | 1 participants |
| Vehicle | Number of LUCENTIS® Retreatment Needs Identified Required up to Day 84 | 0 retreatment injections | 12 participants |
| Vehicle | Number of LUCENTIS® Retreatment Needs Identified Required up to Day 84 | 2 retreatment injections | 6 participants |
| Vehicle | Number of LUCENTIS® Retreatment Needs Identified Required up to Day 84 | 1 retreatment injection | 18 participants |
Secondary
Number of Subjects Requiring LUCENTIS® Retreatment at Days 28 and 56
The number of LUCENTIS® retreatment needs identified before or at the Day 28 and Day 56 visits (even if retreatment was applied at a later visit) for each subject was used in the analysis.
Time frame: Day 28, Day 56
Population: Extended PPS-A4
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LHA510 | Number of Subjects Requiring LUCENTIS® Retreatment at Days 28 and 56 | Day 28 | 5 Participants |
| LHA510 | Number of Subjects Requiring LUCENTIS® Retreatment at Days 28 and 56 | Day 56 | 21 Participants |
| Vehicle | Number of Subjects Requiring LUCENTIS® Retreatment at Days 28 and 56 | Day 28 | 8 Participants |
| Vehicle | Number of Subjects Requiring LUCENTIS® Retreatment at Days 28 and 56 | Day 56 | 19 Participants |
Secondary
Plasma Concentration of LHA510 and CRA398
Samples collected from subjects, after multiple topical ocular dosing of LHA510, were analyzed to determine concentrations of LHA510 and its metabolite, CRA398. Plasma LHA510 and CRA398 concentrations were quantitated by a validated liquid chromatography-tandem mass spectroscopy assay method. Below the limit of quantification (BLQ) is treated as zero.
Time frame: Day 28, Day 84
Population: This analysis population includes all subjects who were treated with LHA510, had at least 1 serum sample following exposure to the IP, and had no known specimen collection or analytical deviations, as identified by the Pharmacokineticist, that would have affected the integrity of the data \[Pharmacokinetics (PK) Analysis Set\].
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LHA510 | Plasma Concentration of LHA510 and CRA398 | Day 28, BID | 0.0746 ng/mL | Standard Deviation 0.0483 |
| LHA510 | Plasma Concentration of LHA510 and CRA398 | Day 84, QD | 0.0403 ng/mL | Standard Deviation 0.0225 |
| LHA510 | Plasma Concentration of LHA510 and CRA398 | Day 84, TID | 0.0694 ng/mL | Standard Deviation 0.0439 |
| Vehicle | Plasma Concentration of LHA510 and CRA398 | Day 28, BID | 0.0257 ng/mL | Standard Deviation 0.0287 |
| Vehicle | Plasma Concentration of LHA510 and CRA398 | Day 84, QD | 0 ng/mL | Standard Deviation 0 |
| Vehicle | Plasma Concentration of LHA510 and CRA398 | Day 84, TID | 0.0160 ng/mL | Standard Deviation 0.0179 |
Secondary
Time to First LUCENTIS® Retreatment Need Identification up to Day 84
The time was determined based on the visit of the treatment period when a patient was identified as requiring retreatment with LUCENTIS.
Time frame: Day 14, Day 28, Day 56, Day 84
Population: Extended PPS-A4 who required retreatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LHA510 | Time to First LUCENTIS® Retreatment Need Identification up to Day 84 | Day 14 | 0 Participants |
| LHA510 | Time to First LUCENTIS® Retreatment Need Identification up to Day 84 | Day 56 | 16 Participants |
| LHA510 | Time to First LUCENTIS® Retreatment Need Identification up to Day 84 | Day 84 | 4 Participants |
| LHA510 | Time to First LUCENTIS® Retreatment Need Identification up to Day 84 | Day 28 | 5 Participants |
| Vehicle | Time to First LUCENTIS® Retreatment Need Identification up to Day 84 | Day 84 | 6 Participants |
| Vehicle | Time to First LUCENTIS® Retreatment Need Identification up to Day 84 | Day 14 | 0 Participants |
| Vehicle | Time to First LUCENTIS® Retreatment Need Identification up to Day 84 | Day 28 | 8 Participants |
| Vehicle | Time to First LUCENTIS® Retreatment Need Identification up to Day 84 | Day 56 | 11 Participants |