Clinical trial NCT01527500: Intravitreal LFG316 in Patients With Age-related Macular Degeneration (AMD)
Official title: A Multicenter, Randomized, Sham-control, Proof-of-concept Study of Intravitreal LFG316 in Patients With Geographic Atrophy Associated With Age-related Macular Degeneration
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Geographic Atrophy
Age-related Macular Degeneration
Keywords: AMD
Age-related Macular Degeneration
geographic atrophy
GA
Dry AMD
Blindness
Drusen
GA lesion
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-02-07
Enrollment: 158
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Part A: Geographic Atrophy (GA) Lesion Growth Measured by Fundus Autofluorescence (FAF) From Baseline to Day 505
timeFrame: Day 1 to Day 505 (starting from the day of first intravitreal injection until Day 505)
measure: Part A: Sensitivity Analysis of the Primary End Point: Mixed Effects Model for Repeated Measurements on GA Lesion Growth Measured by Fundus Autoflourescence
timeFrame: The primary objective was from Day 1 to Day 337, however data was captured to Day 505 as exploratory objective
measure: Part B: Safety and Tolerability of a Single Intravitreal (IVT) Dose of 10 mg/100 μL of LFG316 in Patients With Advanced AMD).
timeFrame: Day 1 to Day 85
Secondary outcomes:
measure: Part A: Change From Baseline in GA Lesions Growth Measured by Fundus Autofluorescence
timeFrame: Day 1 to Day 169 and Day 505 (starting from the day of first intravitreal injection until Day 505)
measure: 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
timeFrame: Baseline Day 1, Day 169, Day 337 to Day 505
measure: 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
timeFrame: Baseline Day 1, Day 169, Day 337 to Day 505
measure: Part A: Concentrations of Total LFG316 in Blood During the Course of the Study
timeFrame: Day 1 to Day 559 (starting from the day of first intravitreal injection to day 559)
measure: Part A: Concentrations of Total C5 in Blood During the Course of the Study
timeFrame: Day 1 to Day 559 (starting from the day of first intravitreal injection to day 559)
measure: Part B: AUC (Area Under the Curve) - Summary Statistics for PK Parameters
timeFrame: Day 1 to Day 85 (starting from the day of first intravitreal injection to day 85)
measure: Tmax (hr)
timeFrame: Day 1 to Day 85 (starting from the day of first intravitreal injection to day 85)
measure: Part B: Cmax - Summary Statistic for PK Parameters
timeFrame: Day 1 to Day 85 (starting from the day of first intravitreal injection to day 85)
measure: Part B: Cmax_D - Summary Statistic for PK Parameters
timeFrame: Day 1 to Day 85 (starting from the day of first intravitreal injection to day 85)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Novartis Investigative Site
state: Arizona
city: Phoenix
country: United States
facility: Novartis Investigative Site
state: Arizona
city: Tucson
country: United States
facility: Novartis Investigative Site
state: Arizona
city: Beverly Hills
country: United States
facility: Novartis Investigative Site
state: California
city: Pasadena
country: United States
facility: Novartis Investigative Site
state: California
city: Sacramento
country: United States
facility: Novartis Investigative Site
state: California
city: Colorado Springs
country: United States
facility: Novartis Investigative Site
state: Colorado
city: Fort Myers
country: United States
facility: Novartis Investigative Site
state: Florida
city: Miami
country: United States
facility: Novartis Investigative Site
state: Florida
city: Winter Haven
country: United States
facility: Novartis Investigative Site
state: Florida
city: Atlanta
country: United States
facility: Novartis Investigative Site
state: Georgia
city: Leawood
country: United States
facility: Novartis Investigative Site
state: Kansas
city: Boston
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Grand Rapids
country: United States
facility: Novartis Investigative Site
state: Michigan
city: Jackson
country: United States
facility: Novartis Investigative Site
state: Michigan
city: Charlotte
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Cincinnati
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Cleveland
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Silverdale
country: United States
facility: Novartis Investigative Site
state: Washington
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: