Geographic Atrophy, Age-related Macular Degeneration
Conditions
Keywords
AMD, Age-related Macular Degeneration, geographic atrophy, GA, Dry AMD, Blindness, Drusen, GA lesion
Brief summary
This study was conducted in two parts; Part A and Part B: Part B was initially planned to include two cohorts. Cohort 2 was cancelled following an interim analysis for efficacy in Part A of the study, and not due to any safety issues or concerns. Cohort 2 is not referred to again and part B cohort 1 is referred to as part B alone in the remainder of the document and is the subject of this report. Part B was conducted to assess the safety and tolerability of a single intravitreal (IVT) LFG316 10 mg/100 µL injection. There was no efficacy evaluation in Part B. The study employed a multicenter, randomized, sham - controlled, single masked design. Eight patients with advanced AMD were planned to be randomized in a 3:1 ratio to receive a single IVT dose of LFG316 (10 mg/100 µL) or sham injection. Patients assigned to a sham injection were treated the same as those assigned to LFG316, except that the hub of an empty syringe (without needle) was placed against the eye instead of the IVT injection.
Interventions
DRUGLFG316
LFG316 5 mg/50 μL solution for IVT injection,
DRUGSham
Sham injection (akin to intravitreal injection but without intravitreal needle; no investigational drug given)
DRUGLFG316 Lower dose
LFG316 5 mg/50 μL solution for IVT Injection
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of AMD if enrolled in Part B of study * Geographic atrophy in at least one eye if enrolled in Part A of study * ETDRS best corrected visual acuity of 60 letters or worse (\ ≤ 20/63)
Exclusion criteria
* Retinal disease other than AMD * History of choroidal neovascularization * Severe cataract * History of infectious uveitis or endophthalmitis * Eye surgery in the non-study eye within 30 days prior to study * Eye surgery or IVT injection in the study eye within 90 days prior to study * Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Geographic Atrophy (GA) Lesion Growth Measured by Fundus Autofluorescence (FAF) From Baseline to Day 505 | Day 1 to Day 505 (starting from the day of first intravitreal injection until Day 505) | Geographic atrophy (GA) lesion growth measured by fundus autofluorescence (FAF) from baseline to Day 505. |
| Part A: Sensitivity Analysis of the Primary End Point: Mixed Effects Model for Repeated Measurements on GA Lesion Growth Measured by Fundus Autoflourescence | The primary objective was from Day 1 to Day 337, however data was captured to Day 505 as exploratory objective | Number is the Estimated Difference (95% CI) in lesion size. |
| Part B: Safety and Tolerability of a Single Intravitreal (IVT) Dose of 10 mg/100 μL of LFG316 in Patients With Advanced AMD). | Day 1 to Day 85 | This primary outcome (for Part B) is reported under the Adverse Events section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Concentrations of Total LFG316 in Blood During the Course of the Study | Day 1 to Day 559 (starting from the day of first intravitreal injection to day 559) | Summary statistic of total LFG316 concentrations (pharmacokinetic analysis set) n=number of participants, h=hours after the last administered dose e.g.; 0.0 means just before dosing. If the mean concentration is 0.00, that means there is no drug in the bloodstream |
| Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 1 to Day 559 (starting from the day of first intravitreal injection to day 559) | Summary statistic of total C5 concentrations n=number of participants, h=scheduled sampling time |
| Part B: AUC (Area Under the Curve) - Summary Statistics for PK Parameters | Day 1 to Day 85 (starting from the day of first intravitreal injection to day 85) | Summary statistic of total LFG316 concentrations (pharmacokinetic analysis set) n=number of participants, h=scheduled sampling time |
| Part A: Change From Baseline in GA Lesions Growth Measured by Fundus Autofluorescence | Day 1 to Day 169 and Day 505 (starting from the day of first intravitreal injection until Day 505) | Mean change in GA lesion growth from baseline to Day 169 and Day 505. |
| Part B: Cmax - Summary Statistic for PK Parameters | Day 1 to Day 85 (starting from the day of first intravitreal injection to day 85) | Summary statistic for Part B of total LFG316 concentrations (pharmacokinetic analysis set) Cmax is the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated and before the administration of a second dose |
| Part B: Cmax_D - Summary Statistic for PK Parameters | Day 1 to Day 85 (starting from the day of first intravitreal injection to day 85) | Cmax\_D=ng/mL/mg |
| Tmax (hr) | Day 1 to Day 85 (starting from the day of first intravitreal injection to day 85) | PART B: Tmax (Time of Maximum concentration observed) This is the highest concentration of drug in the blood that is measured after a dose. Cmax usually happens within a few hours after the dose is taken. The time that Cmax happens is referred to as Tmax. For some antiretroviral drugs, a high Cmax is thought to increase the risk of side effects from the drug. |
| Part A: Change in Best Corrected Visual Acuity (BCVA) as Measured by the EDTRS (Early Treatment of Diabetic Retinopathy Study) Scale From Baseline to Days 169, 337 & 505 in Patients Receiving Every 28 Days, Successive IVT Doses of LFG316 Compared to Sham | Baseline Day 1, Day 169, Day 337 to Day 505 | Part A: Summary of best corrected visual acuity over time, statistical analysis of change in best corrected visual acuity over time Parameter: Visual Acuity (EDTRS letter) BCVA scale is 0-100, worst is 0 and best 100 Eye: STUDY |
| Part A: Summary of Best Corrected Visual Acuity Over Time, Statistical Analysis of Change in Best Corrected Visual Acuity Over Time Parameter: Visual Acuity (EDTRS Letter) BCVA Scale is 0-100, Worst is 0 and Best 100 Eye: FELLOW | Baseline Day 1, Day 169, Day 337 to Day 505 | Part A: Summary of best corrected visual acuity over time, statistical analysis of change in best corrected visual acuity over time Parameter: Visual Acuity (EDTRS letter) BCVA scale is 0-100, worst is 0 and best 100 Eye: FELLOW |
Countries
United States
Participant flow
Recruitment details
Study conducted in 2 parts: Part A & Part B. Part A evaluated safety & efficacy of multiple 5 mg/50 µL doses of intravitreal (IVT) LFG316 against sham every 28 days for 505 days Part B evaluated the safety and pharmacokinetics of a single IVT dose of 10 mg/100 µL of LFG316
Participants by arm
| Arm | Count |
|---|---|
| Part A- LFG316 5 mg LFG316 5 mg injection every 28 days for a total of 12 injections | 99 |
| Part A- Sham sham injection every 28 days for a total of 12 injections | 51 |
| Part B- LFG316 10 mg Single LFG316 10 mg Injection | 7 |
| Part B- Sham Single Sham injection | 1 |
| Total | 158 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Part A | Administrative | 11 | 7 |
| Part A | Adverse Event | 4 | 2 |
| Part A | Death | 4 | 1 |
| Part A | Lost to Follow-up | 0 | 1 |
| Part A | Protocol Deviation | 9 | 2 |
| Part A | Withdrawal by Subject | 2 | 0 |
| Part B | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Part A- LFG316 5 mg | Part A- Sham | Part B- LFG316 10 mg | Part B- Sham | Total |
|---|---|---|---|---|---|
| Age, Continuous | 78.6 years STANDARD_DEVIATION 7.5 | 80.8 years STANDARD_DEVIATION 6.5 | 84.1 years STANDARD_DEVIATION 3.8 | 81.0 years | 79.4 years STANDARD_DEVIATION 7.2 |
| Sex: Female, Male Female | 58 Participants | 32 Participants | 6 Participants | 1 Participants | 97 Participants |
| Sex: Female, Male Male | 41 Participants | 19 Participants | 1 Participants | 0 Participants | 61 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 | 98 / 99 | 42 / 51 | 4 / 7 | 1 / 1 |
| serious Total, serious adverse events | 27 / 99 | 11 / 51 | 1 / 7 | 0 / 1 |
Outcome results
Primary
Part A: Geographic Atrophy (GA) Lesion Growth Measured by Fundus Autofluorescence (FAF) From Baseline to Day 505
Geographic atrophy (GA) lesion growth measured by fundus autofluorescence (FAF) from baseline to Day 505.
Time frame: Day 1 to Day 505 (starting from the day of first intravitreal injection until Day 505)
Population: Pharmacodynamic analysis set (PD) which includes all patients with at least one dose of study drug and evaluable PD data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LFG316 | Part A: Geographic Atrophy (GA) Lesion Growth Measured by Fundus Autofluorescence (FAF) From Baseline to Day 505 | 1.95 mm^2 | Standard Deviation 1.01 |
| Sham | Part A: Geographic Atrophy (GA) Lesion Growth Measured by Fundus Autofluorescence (FAF) From Baseline to Day 505 | 1.58 mm^2 | Standard Deviation 1.12 |
Primary
Part A: Sensitivity Analysis of the Primary End Point: Mixed Effects Model for Repeated Measurements on GA Lesion Growth Measured by Fundus Autoflourescence
Number is the Estimated Difference (95% CI) in lesion size.
Time frame: The primary objective was from Day 1 to Day 337, however data was captured to Day 505 as exploratory objective
Population: PD Set which included patients who had at least one dose of study drug and had evaluable PD Data.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| LFG316 | Part A: Sensitivity Analysis of the Primary End Point: Mixed Effects Model for Repeated Measurements on GA Lesion Growth Measured by Fundus Autoflourescence | Bilateral Day 169 | 0.975 mm^2 |
| LFG316 | Part A: Sensitivity Analysis of the Primary End Point: Mixed Effects Model for Repeated Measurements on GA Lesion Growth Measured by Fundus Autoflourescence | Bilateral Day 337 | 1.825 mm^2 |
| LFG316 | Part A: Sensitivity Analysis of the Primary End Point: Mixed Effects Model for Repeated Measurements on GA Lesion Growth Measured by Fundus Autoflourescence | Bilateral Day 505 | 2.674 mm^2 |
| LFG316 | Part A: Sensitivity Analysis of the Primary End Point: Mixed Effects Model for Repeated Measurements on GA Lesion Growth Measured by Fundus Autoflourescence | Overall Day 169 | 1.036 mm^2 |
| LFG316 | Part A: Sensitivity Analysis of the Primary End Point: Mixed Effects Model for Repeated Measurements on GA Lesion Growth Measured by Fundus Autoflourescence | Overall Day 337 | 1.885 mm^2 |
| LFG316 | Part A: Sensitivity Analysis of the Primary End Point: Mixed Effects Model for Repeated Measurements on GA Lesion Growth Measured by Fundus Autoflourescence | Overall Day 505 | 2.735 mm^2 |
| Sham | Part A: Sensitivity Analysis of the Primary End Point: Mixed Effects Model for Repeated Measurements on GA Lesion Growth Measured by Fundus Autoflourescence | Overall Day 505 | 2.530 mm^2 |
| Sham | Part A: Sensitivity Analysis of the Primary End Point: Mixed Effects Model for Repeated Measurements on GA Lesion Growth Measured by Fundus Autoflourescence | Bilateral Day 169 | 0.913 mm^2 |
| Sham | Part A: Sensitivity Analysis of the Primary End Point: Mixed Effects Model for Repeated Measurements on GA Lesion Growth Measured by Fundus Autoflourescence | Overall Day 169 | 0.937 mm^2 |
| Sham | Part A: Sensitivity Analysis of the Primary End Point: Mixed Effects Model for Repeated Measurements on GA Lesion Growth Measured by Fundus Autoflourescence | Overall Day 337 | 1.734 mm^2 |
| Sham | Part A: Sensitivity Analysis of the Primary End Point: Mixed Effects Model for Repeated Measurements on GA Lesion Growth Measured by Fundus Autoflourescence | Bilateral Day 337 | 1.710 mm^2 |
| Sham | Part A: Sensitivity Analysis of the Primary End Point: Mixed Effects Model for Repeated Measurements on GA Lesion Growth Measured by Fundus Autoflourescence | Bilateral Day 505 | 2.506 mm^2 |
| LFG316 5 Mg-Sham | Part A: Sensitivity Analysis of the Primary End Point: Mixed Effects Model for Repeated Measurements on GA Lesion Growth Measured by Fundus Autoflourescence | Bilateral Day 337 | 0.115 mm^2 |
| LFG316 5 Mg-Sham | Part A: Sensitivity Analysis of the Primary End Point: Mixed Effects Model for Repeated Measurements on GA Lesion Growth Measured by Fundus Autoflourescence | Bilateral Day 505 | 0.168 mm^2 |
| LFG316 5 Mg-Sham | Part A: Sensitivity Analysis of the Primary End Point: Mixed Effects Model for Repeated Measurements on GA Lesion Growth Measured by Fundus Autoflourescence | Overall Day 505 | 0.205 mm^2 |
| LFG316 5 Mg-Sham | Part A: Sensitivity Analysis of the Primary End Point: Mixed Effects Model for Repeated Measurements on GA Lesion Growth Measured by Fundus Autoflourescence | Overall Day 169 | 0.099 mm^2 |
| LFG316 5 Mg-Sham | Part A: Sensitivity Analysis of the Primary End Point: Mixed Effects Model for Repeated Measurements on GA Lesion Growth Measured by Fundus Autoflourescence | Bilateral Day 169 | 0.062 mm^2 |
| LFG316 5 Mg-Sham | Part A: Sensitivity Analysis of the Primary End Point: Mixed Effects Model for Repeated Measurements on GA Lesion Growth Measured by Fundus Autoflourescence | Overall Day 337 | 0.152 mm^2 |
Primary
Part B: Safety and Tolerability of a Single Intravitreal (IVT) Dose of 10 mg/100 μL of LFG316 in Patients With Advanced AMD).
This primary outcome (for Part B) is reported under the Adverse Events section.
Time frame: Day 1 to Day 85
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LFG316 | Part B: Safety and Tolerability of a Single Intravitreal (IVT) Dose of 10 mg/100 μL of LFG316 in Patients With Advanced AMD). | Total # Affected by any Serious Adverse Event | 27 number of patients |
| LFG316 | Part B: Safety and Tolerability of a Single Intravitreal (IVT) Dose of 10 mg/100 μL of LFG316 in Patients With Advanced AMD). | Total # at Risk by any Serious Adverse Event | 99 number of patients |
| Sham | Part B: Safety and Tolerability of a Single Intravitreal (IVT) Dose of 10 mg/100 μL of LFG316 in Patients With Advanced AMD). | Total # at Risk by any Serious Adverse Event | 51 number of patients |
| Sham | Part B: Safety and Tolerability of a Single Intravitreal (IVT) Dose of 10 mg/100 μL of LFG316 in Patients With Advanced AMD). | Total # Affected by any Serious Adverse Event | 11 number of patients |
| LFG316 5 Mg-Sham | Part B: Safety and Tolerability of a Single Intravitreal (IVT) Dose of 10 mg/100 μL of LFG316 in Patients With Advanced AMD). | Total # at Risk by any Serious Adverse Event | 7 number of patients |
| LFG316 5 Mg-Sham | Part B: Safety and Tolerability of a Single Intravitreal (IVT) Dose of 10 mg/100 μL of LFG316 in Patients With Advanced AMD). | Total # Affected by any Serious Adverse Event | 1 number of patients |
| Sham - Part B | Part B: Safety and Tolerability of a Single Intravitreal (IVT) Dose of 10 mg/100 μL of LFG316 in Patients With Advanced AMD). | Total # Affected by any Serious Adverse Event | 0 number of patients |
| Sham - Part B | Part B: Safety and Tolerability of a Single Intravitreal (IVT) Dose of 10 mg/100 μL of LFG316 in Patients With Advanced AMD). | Total # at Risk by any Serious Adverse Event | 1 number of patients |
Secondary
Part A: Change From Baseline in GA Lesions Growth Measured by Fundus Autofluorescence
Mean change in GA lesion growth from baseline to Day 169 and Day 505.
Time frame: Day 1 to Day 169 and Day 505 (starting from the day of first intravitreal injection until Day 505)
Population: PD Set which included patients who had at least one dose of study drug and had evaluable PD Data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LFG316 | Part A: Change From Baseline in GA Lesions Growth Measured by Fundus Autofluorescence | Day 169 (n=68, 37) | 0.99 mm^2 | Standard Deviation 0.6 |
| LFG316 | Part A: Change From Baseline in GA Lesions Growth Measured by Fundus Autofluorescence | Day 505 (n=38, 18) | 2.78 mm^2 | Standard Deviation 1.28 |
| Sham | Part A: Change From Baseline in GA Lesions Growth Measured by Fundus Autofluorescence | Day 169 (n=68, 37) | 0.88 mm^2 | Standard Deviation 0.77 |
| Sham | Part A: Change From Baseline in GA Lesions Growth Measured by Fundus Autofluorescence | Day 505 (n=38, 18) | 2.03 mm^2 | Standard Deviation 1 |
Secondary
Part A: Change in Best Corrected Visual Acuity (BCVA) as Measured by the EDTRS (Early Treatment of Diabetic Retinopathy Study) Scale From Baseline to Days 169, 337 & 505 in Patients Receiving Every 28 Days, Successive IVT Doses of LFG316 Compared to Sham
Part A: Summary of best corrected visual acuity over time, statistical analysis of change in best corrected visual acuity over time Parameter: Visual Acuity (EDTRS letter) BCVA scale is 0-100, worst is 0 and best 100 Eye: STUDY
Time frame: Baseline Day 1, Day 169, Day 337 to Day 505
Population: PD analysis set which includes all patients with at least one dose of study drug and evaluable PD data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LFG316 | Part A: Change in Best Corrected Visual Acuity (BCVA) as Measured by the EDTRS (Early Treatment of Diabetic Retinopathy Study) Scale From Baseline to Days 169, 337 & 505 in Patients Receiving Every 28 Days, Successive IVT Doses of LFG316 Compared to Sham | Baseline Day 1 (n=74, 38) | 43.91 ETDRS letters | Standard Deviation 12.93 |
| LFG316 | Part A: Change in Best Corrected Visual Acuity (BCVA) as Measured by the EDTRS (Early Treatment of Diabetic Retinopathy Study) Scale From Baseline to Days 169, 337 & 505 in Patients Receiving Every 28 Days, Successive IVT Doses of LFG316 Compared to Sham | Day 169 (n=71, 36) | 48.38 ETDRS letters | Standard Deviation 11.05 |
| LFG316 | Part A: Change in Best Corrected Visual Acuity (BCVA) as Measured by the EDTRS (Early Treatment of Diabetic Retinopathy Study) Scale From Baseline to Days 169, 337 & 505 in Patients Receiving Every 28 Days, Successive IVT Doses of LFG316 Compared to Sham | Day 337 (n=53, 30) | 47.49 ETDRS letters | Standard Deviation 11.25 |
| LFG316 | Part A: Change in Best Corrected Visual Acuity (BCVA) as Measured by the EDTRS (Early Treatment of Diabetic Retinopathy Study) Scale From Baseline to Days 169, 337 & 505 in Patients Receiving Every 28 Days, Successive IVT Doses of LFG316 Compared to Sham | Day 505 (n=40, 23) | 44.73 ETDRS letters | Standard Deviation 11.29 |
| Sham | Part A: Change in Best Corrected Visual Acuity (BCVA) as Measured by the EDTRS (Early Treatment of Diabetic Retinopathy Study) Scale From Baseline to Days 169, 337 & 505 in Patients Receiving Every 28 Days, Successive IVT Doses of LFG316 Compared to Sham | Day 505 (n=40, 23) | 43.78 ETDRS letters | Standard Deviation 14.11 |
| Sham | Part A: Change in Best Corrected Visual Acuity (BCVA) as Measured by the EDTRS (Early Treatment of Diabetic Retinopathy Study) Scale From Baseline to Days 169, 337 & 505 in Patients Receiving Every 28 Days, Successive IVT Doses of LFG316 Compared to Sham | Baseline Day 1 (n=74, 38) | 40.26 ETDRS letters | Standard Deviation 14.97 |
| Sham | Part A: Change in Best Corrected Visual Acuity (BCVA) as Measured by the EDTRS (Early Treatment of Diabetic Retinopathy Study) Scale From Baseline to Days 169, 337 & 505 in Patients Receiving Every 28 Days, Successive IVT Doses of LFG316 Compared to Sham | Day 337 (n=53, 30) | 42.97 ETDRS letters | Standard Deviation 14.23 |
| Sham | Part A: Change in Best Corrected Visual Acuity (BCVA) as Measured by the EDTRS (Early Treatment of Diabetic Retinopathy Study) Scale From Baseline to Days 169, 337 & 505 in Patients Receiving Every 28 Days, Successive IVT Doses of LFG316 Compared to Sham | Day 169 (n=71, 36) | 42.50 ETDRS letters | Standard Deviation 15.14 |
Secondary
Part A: Concentrations of Total C5 in Blood During the Course of the Study
Summary statistic of total C5 concentrations n=number of participants, h=scheduled sampling time
Time frame: Day 1 to Day 559 (starting from the day of first intravitreal injection to day 559)
Population: PD Analysis includes patients who received at least one dose of study drug with evaluable PD data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LFG316 | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 113 (n=83, 49), h=0 | 153000 ng/mL | Standard Deviation 46200 |
| LFG316 | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 281 (n=69, 34), h=0 | 145000 ng/mL | Standard Deviation 28000 |
| LFG316 | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 29 (n=94, 47), h=0 | 145000 ng/mL | Standard Deviation 31200 |
| LFG316 | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 309 (n=68, 32), h=0 | 151000 ng/mL | Standard Deviation 45200 |
| LFG316 | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 141 (n=84, 45), h=0 | 144000 ng/mL | Standard Deviation 32600 |
| LFG316 | Part A: Concentrations of Total C5 in Blood During the Course of the Study | (n=22, 12), h=672 | 137000 ng/mL | Standard Deviation 31000 |
| LFG316 | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 1 (n=99, 51), h=0 | 147000 ng/mL | Standard Deviation 28900 |
| LFG316 | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 365 (n=40, 24), h=0 | 146000 ng/mL | Standard Deviation 29300 |
| LFG316 | Part A: Concentrations of Total C5 in Blood During the Course of the Study | (n=9, 3), h=672 | 146000 ng/mL | Standard Deviation 288000 |
| LFG316 | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 393 (n=42, 22), h=0 | 145000 ng/mL | Standard Deviation 23700 |
| LFG316 | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 57 (n=96, 49), h=0 | 147000 ng/mL | Standard Deviation 29300 |
| LFG316 | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 421(n=40, 22), h=0 | 149000 ng/mL | Standard Deviation 24700 |
| LFG316 | Part A: Concentrations of Total C5 in Blood During the Course of the Study | (n=91, 49), h=336 | 149000 ng/mL | Standard Deviation 41100 |
| LFG316 | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 449 (n=40, 23), h=0 | 160000 ng/mL | Standard Deviation 41200 |
| LFG316 | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 197 (n=73, 36), h=0 | 143000 ng/mL | Standard Deviation 27300 |
| LFG316 | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 477 (n=39, 21), h=0 | 148000 ng/mL | Standard Deviation 20400 |
| LFG316 | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 85 (n=93, 46), h=0 | 154000 ng/mL | Standard Deviation 42500 |
| LFG316 | Part A: Concentrations of Total C5 in Blood During the Course of the Study | (n=41, 21), h=672 | 158000 ng/mL | Standard Deviation 37800 |
| LFG316 | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 225 (n=71, 34), h=0 | 152000 ng/mL | Standard Deviation 51600 |
| LFG316 | Part A: Concentrations of Total C5 in Blood During the Course of the Study | (n=38, 22), h=1968 | 198000 ng/mL | Standard Deviation 82700 |
| LFG316 | Part A: Concentrations of Total C5 in Blood During the Course of the Study | (n= 97, 51), h= 24 | 143000 ng/mL | Standard Deviation 31200 |
| LFG316 | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 309 (n=16, 10), h=2688 | 135000 ng/mL | Standard Deviation 19600 |
| LFG316 | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 253 (n=42, 18), h=0 | 144000 ng/mL | Standard Deviation 38500 |
| LFG316 | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 337 (n=44, 24), h-0 | 147000 ng/mL | Standard Deviation 27900 |
| LFG316 | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 169 (n=68, 37), h=0 | 147000 ng/mL | Standard Deviation 39400 |
| Sham | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 337 (n=44, 24), h-0 | 137000 ng/mL | Standard Deviation 36200 |
| Sham | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 1 (n=99, 51), h=0 | 142000 ng/mL | Standard Deviation 25500 |
| Sham | Part A: Concentrations of Total C5 in Blood During the Course of the Study | (n= 97, 51), h= 24 | 139000 ng/mL | Standard Deviation 27600 |
| Sham | Part A: Concentrations of Total C5 in Blood During the Course of the Study | (n=91, 49), h=336 | 136000 ng/mL | Standard Deviation 25600 |
| Sham | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 29 (n=94, 47), h=0 | 142000 ng/mL | Standard Deviation 33900 |
| Sham | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 57 (n=96, 49), h=0 | 148000 ng/mL | Standard Deviation 40400 |
| Sham | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 85 (n=93, 46), h=0 | 144000 ng/mL | Standard Deviation 39100 |
| Sham | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 113 (n=83, 49), h=0 | 146000 ng/mL | Standard Deviation 42100 |
| Sham | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 141 (n=84, 45), h=0 | 141000 ng/mL | Standard Deviation 25600 |
| Sham | Part A: Concentrations of Total C5 in Blood During the Course of the Study | (n=9, 3), h=672 | 135000 ng/mL | Standard Deviation 8000 |
| Sham | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 169 (n=68, 37), h=0 | 144000 ng/mL | Standard Deviation 38600 |
| Sham | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 197 (n=73, 36), h=0 | 139000 ng/mL | Standard Deviation 32500 |
| Sham | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 225 (n=71, 34), h=0 | 140000 ng/mL | Standard Deviation 33600 |
| Sham | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 253 (n=42, 18), h=0 | 129000 ng/mL | Standard Deviation 31000 |
| Sham | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 281 (n=69, 34), h=0 | 144000 ng/mL | Standard Deviation 35300 |
| Sham | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 309 (n=68, 32), h=0 | 148000 ng/mL | Standard Deviation 39400 |
| Sham | Part A: Concentrations of Total C5 in Blood During the Course of the Study | (n=22, 12), h=672 | 145000 ng/mL | Standard Deviation 33200 |
| Sham | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 365 (n=40, 24), h=0 | 131000 ng/mL | Standard Deviation 29300 |
| Sham | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 393 (n=42, 22), h=0 | 132000 ng/mL | Standard Deviation 28500 |
| Sham | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 421(n=40, 22), h=0 | 141000 ng/mL | Standard Deviation 34200 |
| Sham | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 449 (n=40, 23), h=0 | 144000 ng/mL | Standard Deviation 27000 |
| Sham | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 477 (n=39, 21), h=0 | 156000 ng/mL | Standard Deviation 53900 |
| Sham | Part A: Concentrations of Total C5 in Blood During the Course of the Study | (n=41, 21), h=672 | 155000 ng/mL | Standard Deviation 59000 |
| Sham | Part A: Concentrations of Total C5 in Blood During the Course of the Study | (n=38, 22), h=1968 | 186000 ng/mL | Standard Deviation 79600 |
| Sham | Part A: Concentrations of Total C5 in Blood During the Course of the Study | Day 309 (n=16, 10), h=2688 | 135000 ng/mL | Standard Deviation 18800 |
Secondary
Part A: Concentrations of Total LFG316 in Blood During the Course of the Study
Summary statistic of total LFG316 concentrations (pharmacokinetic analysis set) n=number of participants, h=hours after the last administered dose e.g.; 0.0 means just before dosing. If the mean concentration is 0.00, that means there is no drug in the bloodstream
Time frame: Day 1 to Day 559 (starting from the day of first intravitreal injection to day 559)
Population: Pharmacokinetic analysis set: The PK analysis set included all patients with at least one dose of study drug and evaluable PK data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LFG316 | Part A: Concentrations of Total LFG316 in Blood During the Course of the Study | Day 1 (n=99), h=0 | 0.00 ng/mL | Standard Deviation 0 |
| LFG316 | Part A: Concentrations of Total LFG316 in Blood During the Course of the Study | Day 1(n= 97), h= 24 | 293 ng/mL | Standard Deviation 332 |
| LFG316 | Part A: Concentrations of Total LFG316 in Blood During the Course of the Study | Day 1(n=91), h=336 | 560 ng/mL | Standard Deviation 238 |
| LFG316 | Part A: Concentrations of Total LFG316 in Blood During the Course of the Study | Day 29 (n=94), h=0 | 289 ng/mL | Standard Deviation 214 |
| LFG316 | Part A: Concentrations of Total LFG316 in Blood During the Course of the Study | Day 57 (n=96), h=0 | 382 ng/mL | Standard Deviation 218 |
| LFG316 | Part A: Concentrations of Total LFG316 in Blood During the Course of the Study | Day 85 (n=93), h=0 | 436 ng/mL | Standard Deviation 210 |
| LFG316 | Part A: Concentrations of Total LFG316 in Blood During the Course of the Study | Day 113 (n=83), h=0 | 433 ng/mL | Standard Deviation 219 |
| LFG316 | Part A: Concentrations of Total LFG316 in Blood During the Course of the Study | Day 141 (n=84), h=0 | 451 ng/mL | Standard Deviation 218 |
| LFG316 | Part A: Concentrations of Total LFG316 in Blood During the Course of the Study | Day 141 (n=9), h=672 | 482 ng/mL | Standard Deviation 174 |
| LFG316 | Part A: Concentrations of Total LFG316 in Blood During the Course of the Study | Day 169 (n=68), h=0 | 446 ng/mL | Standard Deviation 204 |
| LFG316 | Part A: Concentrations of Total LFG316 in Blood During the Course of the Study | Day 197 (n=73), h=0 | 434 ng/mL | Standard Deviation 231 |
| LFG316 | Part A: Concentrations of Total LFG316 in Blood During the Course of the Study | Day 225 (n=71), h=0 | 471 ng/mL | Standard Deviation 224 |
| LFG316 | Part A: Concentrations of Total LFG316 in Blood During the Course of the Study | Day 253 (n=42), h=0 | 465 ng/mL | Standard Deviation 237 |
| LFG316 | Part A: Concentrations of Total LFG316 in Blood During the Course of the Study | Day 281 (n=69), h=0 | 485 ng/mL | Standard Deviation 274 |
| LFG316 | Part A: Concentrations of Total LFG316 in Blood During the Course of the Study | Day 309 (n=68), h=0 | 447 ng/mL | Standard Deviation 226 |
| LFG316 | Part A: Concentrations of Total LFG316 in Blood During the Course of the Study | Day 309 (n=22), h=672 | 405 ng/mL | Standard Deviation 189 |
| LFG316 | Part A: Concentrations of Total LFG316 in Blood During the Course of the Study | Day 365 (n=40), h=0 | 427 ng/mL | Standard Deviation 288 |
| LFG316 | Part A: Concentrations of Total LFG316 in Blood During the Course of the Study | Day 393 (n=42), h=0 | 464 ng/mL | Standard Deviation 239 |
| LFG316 | Part A: Concentrations of Total LFG316 in Blood During the Course of the Study | Day 421(n=40), h=0 | 471 ng/mL | Standard Deviation 228 |
| LFG316 | Part A: Concentrations of Total LFG316 in Blood During the Course of the Study | Day 449 (n=40), h=0 | 459 ng/mL | Standard Deviation 214 |
| LFG316 | Part A: Concentrations of Total LFG316 in Blood During the Course of the Study | Day 477 (n=39), h=0 | 422 ng/mL | Standard Deviation 236 |
| LFG316 | Part A: Concentrations of Total LFG316 in Blood During the Course of the Study | Day 477 (n=41), h=672 | 439 ng/mL | Standard Deviation 191 |
| LFG316 | Part A: Concentrations of Total LFG316 in Blood During the Course of the Study | Day 477 (n=38), h=1968 | 0.00 ng/mL | Standard Deviation 0 |
| LFG316 | Part A: Concentrations of Total LFG316 in Blood During the Course of the Study | Day 309 (n=16), h=2688 | 0.00 ng/mL | Standard Deviation 0 |
| LFG316 | Part A: Concentrations of Total LFG316 in Blood During the Course of the Study | Day 337 (n=42), h=0 | 435 ng/mL | Standard Deviation 283 |
Secondary
Part A: Summary of Best Corrected Visual Acuity Over Time, Statistical Analysis of Change in Best Corrected Visual Acuity Over Time Parameter: Visual Acuity (EDTRS Letter) BCVA Scale is 0-100, Worst is 0 and Best 100 Eye: FELLOW
Part A: Summary of best corrected visual acuity over time, statistical analysis of change in best corrected visual acuity over time Parameter: Visual Acuity (EDTRS letter) BCVA scale is 0-100, worst is 0 and best 100 Eye: FELLOW
Time frame: Baseline Day 1, Day 169, Day 337 to Day 505
Population: PD analysis set which includes all patients with at least one dose of study drug and evaluable PD data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LFG316 | Part A: Summary of Best Corrected Visual Acuity Over Time, Statistical Analysis of Change in Best Corrected Visual Acuity Over Time Parameter: Visual Acuity (EDTRS Letter) BCVA Scale is 0-100, Worst is 0 and Best 100 Eye: FELLOW | Baseline Day 1 (n=74, 38) | 54.66 ETDRS Letters | Standard Deviation 22.02 |
| LFG316 | Part A: Summary of Best Corrected Visual Acuity Over Time, Statistical Analysis of Change in Best Corrected Visual Acuity Over Time Parameter: Visual Acuity (EDTRS Letter) BCVA Scale is 0-100, Worst is 0 and Best 100 Eye: FELLOW | Day 169 (n=71, 36) | 54.59 ETDRS Letters | Standard Deviation 21.92 |
| LFG316 | Part A: Summary of Best Corrected Visual Acuity Over Time, Statistical Analysis of Change in Best Corrected Visual Acuity Over Time Parameter: Visual Acuity (EDTRS Letter) BCVA Scale is 0-100, Worst is 0 and Best 100 Eye: FELLOW | Day 337 (n=53, 30) | 52.75 ETDRS Letters | Standard Deviation 21.66 |
| LFG316 | Part A: Summary of Best Corrected Visual Acuity Over Time, Statistical Analysis of Change in Best Corrected Visual Acuity Over Time Parameter: Visual Acuity (EDTRS Letter) BCVA Scale is 0-100, Worst is 0 and Best 100 Eye: FELLOW | Day 505 (n=40, 23) | 50.95 ETDRS Letters | Standard Deviation 20.67 |
| Sham | Part A: Summary of Best Corrected Visual Acuity Over Time, Statistical Analysis of Change in Best Corrected Visual Acuity Over Time Parameter: Visual Acuity (EDTRS Letter) BCVA Scale is 0-100, Worst is 0 and Best 100 Eye: FELLOW | Day 505 (n=40, 23) | 49.87 ETDRS Letters | Standard Deviation 19.35 |
| Sham | Part A: Summary of Best Corrected Visual Acuity Over Time, Statistical Analysis of Change in Best Corrected Visual Acuity Over Time Parameter: Visual Acuity (EDTRS Letter) BCVA Scale is 0-100, Worst is 0 and Best 100 Eye: FELLOW | Baseline Day 1 (n=74, 38) | 55.13 ETDRS Letters | Standard Deviation 18.27 |
| Sham | Part A: Summary of Best Corrected Visual Acuity Over Time, Statistical Analysis of Change in Best Corrected Visual Acuity Over Time Parameter: Visual Acuity (EDTRS Letter) BCVA Scale is 0-100, Worst is 0 and Best 100 Eye: FELLOW | Day 337 (n=53, 30) | 53.87 ETDRS Letters | Standard Deviation 18.83 |
| Sham | Part A: Summary of Best Corrected Visual Acuity Over Time, Statistical Analysis of Change in Best Corrected Visual Acuity Over Time Parameter: Visual Acuity (EDTRS Letter) BCVA Scale is 0-100, Worst is 0 and Best 100 Eye: FELLOW | Day 169 (n=71, 36) | 57.33 ETDRS Letters | Standard Deviation 17.89 |
Secondary
Part B: AUC (Area Under the Curve) - Summary Statistics for PK Parameters
Summary statistic of total LFG316 concentrations (pharmacokinetic analysis set) n=number of participants, h=scheduled sampling time
Time frame: Day 1 to Day 85 (starting from the day of first intravitreal injection to day 85)
Population: Pharmacokinetic analysis set: The PK analysis set included all patients with at least one dose of study drug and evaluable PK data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LFG316 | Part B: AUC (Area Under the Curve) - Summary Statistics for PK Parameters | AUCall (hr*ng/mL) | 743000 hr*ng/mL | Standard Deviation 241000 |
| LFG316 | Part B: AUC (Area Under the Curve) - Summary Statistics for PK Parameters | AUClast (hr*ng/mL) | 600000 hr*ng/mL | Standard Deviation 212000 |
Secondary
Part B: Cmax_D - Summary Statistic for PK Parameters
Cmax\_D=ng/mL/mg
Time frame: Day 1 to Day 85 (starting from the day of first intravitreal injection to day 85)
Population: Pharmacokinetic analysis set: The PK analysis set included all patients with at least one dose of study drug and evaluable PK data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LFG316 | Part B: Cmax_D - Summary Statistic for PK Parameters | 101 ng/mL/mg | Standard Deviation 21.3 |
Secondary
Part B: Cmax - Summary Statistic for PK Parameters
Summary statistic for Part B of total LFG316 concentrations (pharmacokinetic analysis set) Cmax is the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated and before the administration of a second dose
Time frame: Day 1 to Day 85 (starting from the day of first intravitreal injection to day 85)
Population: Pharmacokinetic analysis set: The PK analysis set included all patients with at least one dose of study drug and evaluable PK data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LFG316 | Part B: Cmax - Summary Statistic for PK Parameters | 1010 ng/mL | Standard Deviation 213 |
Secondary
Tmax (hr)
PART B: Tmax (Time of Maximum concentration observed) This is the highest concentration of drug in the blood that is measured after a dose. Cmax usually happens within a few hours after the dose is taken. The time that Cmax happens is referred to as Tmax. For some antiretroviral drugs, a high Cmax is thought to increase the risk of side effects from the drug.
Time frame: Day 1 to Day 85 (starting from the day of first intravitreal injection to day 85)
Population: Pharmacokinetic analysis set: The PK analysis set included all patients with at least one dose of study drug and evaluable PK data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LFG316 | Tmax (hr) | 213 hours |