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

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

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.

Sham injection (akin to intravitreal injection but without intravitreal needle; no investigational drug given)

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.

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

Part B: Safety and Tolerability of a Single Intravitreal (IVT) Dose of 10 mg/100 μL of LFG316 in Patients With Advanced AMD).

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

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

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

Summary statistic of total LFG316 concentrations (pharmacokinetic analysis set) n=number of participants, h=scheduled sampling time

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.

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

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

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