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

Phase 2

Completed

Conditions: Geographic Atrophy
Age-related Macular Degeneration

Interventions: Drug: LFG316
Drug: Sham
Drug: LFG316 Lower dose

Registration Number: NCT01527500

Lead Sponsor: Novartis Pharmaceuticals

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 158

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LFG316 higher dose	LFG316	LFG316 10 mg/100 μL
Sham	Sham	Sham injection
LFG316 lower dose	LFG316 Lower dose	LFG316 5 mg/ 50 μL

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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: 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 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
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
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: 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 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