Intravitreal LFG316 in Patients With Age-related Macular Degeneration (AMD)

Study Overview
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Brief Summary
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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.

Official Title
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A Multicenter, Randomized, Sham-control, Proof-of-concept Study of Intravitreal LFG316 in Patients With Geographic Atrophy Associated With Age-related Macular Degeneration

Conditions
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Geographic Atrophy, Age-related Macular Degeneration

Intervention / Treatment
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* Drug: LFG316
* Drug: Sham
* Drug: LFG316 Lower dose


Participation Criteria
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Eligibility Criteria
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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/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LFG316 higher dose<br>LFG316 10 mg/100 μL | Drug: LFG316<br>* LFG316 5 mg/50 μL solution for IVT injection,<br>|
| Sham Comparator: Sham<br>Sham injection | Drug: Sham<br>* Sham injection (akin to intravitreal injection but without intravitreal needle; no investigational drug given)<br>|
| Experimental: LFG316 lower dose<br>LFG316 5 mg/ 50 μL | Drug: LFG316 Lower dose<br>* LFG316 5 mg/50 μL solution for IVT Injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Day 1 to Day 505 (starting from the day of first intravitreal injection until 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 | Number is the Estimated Difference (95% CI) in lesion size. | The primary objective was from Day 1 to Day 337, however data was captured to Day 505 as exploratory objective | 
| 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. | Day 1 to Day 85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Day 1 to Day 169 and Day 505 (starting from the day of first intravitreal injection until Day 505) | 
| 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 | 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 | 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: 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 | Day 1 to Day 559 (starting from the day of first intravitreal injection to day 559) | 
| 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 | Day 1 to Day 559 (starting from the day of first intravitreal injection to day 559) | 
| 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 | Day 1 to Day 85 (starting from the day of first intravitreal injection to day 85) | 
| 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. | Day 1 to Day 85 (starting from the day of first intravitreal injection to day 85) | 
| 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 | Day 1 to Day 85 (starting from the day of first intravitreal injection to day 85) | 
| Part B: Cmax_D - Summary Statistic for PK Parameters | Cmax_D=ng/mL/mg | Day 1 to Day 85 (starting from the day of first intravitreal injection to day 85) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AMD, Age-related Macular Degeneration, geographic atrophy, GA, Dry AMD, Blindness, Drusen, GA lesion