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

Age-related Macular Degeneration Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01527500
• Other study ID #: CLFG316A2203
• Status: Completed
• Phase: Phase 2
• Start date: January 25, 2012
• Est. completion date: June 24, 2015

Study information

• Verified date: March 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 158
• Est. completion date: June 24, 2015
• Est. primary completion date: June 24, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Age-related Macular Degeneration
• Atrophy
• Geographic Atrophy
• Macular Degeneration

Intervention

Drug:
• LFG316
LFG316 5 mg/50 µL solution for IVT injection,
• Sham
Sham injection (akin to intravitreal injection but without intravitreal needle; no investigational drug given)
• LFG316 Lower dose
LFG316 5 mg/50 µL solution for IVT Injection

Locations

Country	Name	City	State
United States	Novartis Investigative Site	Atlanta	Georgia
United States	Novartis Investigative Site	Beverly Hills	California
United States	Novartis Investigative Site	Boston	Massachusetts
United States	Novartis Investigative Site	Charlotte	North Carolina
United States	Novartis Investigative Site	Cincinnati	Ohio
United States	Novartis Investigative Site	Cleveland	Ohio
United States	Novartis Investigative Site	Colorado Springs	Colorado
United States	Novartis Investigative Site	Fort Myers	Florida
United States	Novartis Investigative Site	Grand Rapids	Michigan
United States	Novartis Investigative Site	Jackson	Michigan
United States	Novartis Investigative Site	Leawood	Kansas
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	Pasadena	California
United States	Novartis Investigative Site	Phoenix	Arizona
United States	Novartis Investigative Site	Phoenix	Arizona
United States	Novartis Investigative Site	Sacramento	California
United States	Novartis Investigative Site	Silverdale	Washington
United States	Novartis Investigative Site	Tucson	Arizona
United States	Novartis Investigative Site	Winter Haven	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Day 1 to Day 505 (starting from the day of first intravitreal injection until Day 505)
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.	The primary objective was from Day 1 to Day 337, however data was captured to Day 505 as exploratory objective
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.	Day 1 to Day 85
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.	Day 1 to Day 169 and Day 505 (starting from the day of first intravitreal injection until Day 505)
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	Baseline Day 1, Day 169, Day 337 to Day 505
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	Baseline Day 1, Day 169, Day 337 to Day 505
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	Day 1 to Day 559 (starting from the day of first intravitreal injection to day 559)
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	Day 1 to Day 559 (starting from the day of first intravitreal injection to day 559)
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	Day 1 to Day 85 (starting from the day of first intravitreal injection to day 85)
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.	Day 1 to Day 85 (starting from the day of first intravitreal injection to day 85)
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	Day 1 to Day 85 (starting from the day of first intravitreal injection to day 85)
Secondary	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)

External Links

•   A Plain Language Trial Summary is available on novartisclinicaltrials.com