Safety and Tolerability of Intravenous LFG316 in Wet Age-related Macular Degeneration (AMD).

Study Overview
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Brief Summary
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This study will assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of successive intravenous (IV) doses of LFG316 in eligible patients with neovascular age-related macular degeneration (AMD)

Official Title
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A Multiple Dose, Two-cohort Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Intravenous LFG316 in Patients With Neovascular Age-related Macular Degeneration

Conditions
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Neovascular Age-related Macular Degeneration

Intervention / Treatment
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* Drug: Placebo
* Drug: LFG316
* Drug: LFG316


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Active choroidal neovascular AMD in at least one eye. Exclusion Criteria: Retinal disease other than AMD that, in the investigator's opinion, would interfere with safety or study conduct. Choroidal neovascularization due to a cause other than AMD. In the study eye, media opacity that, in the investigator's opinion, would interfere with study conduct. Any disease or concomitant (or recent) medication expected to cause systemic immunosuppression. History of meningococcal meningitis in the past 10 years, or any history of recurrent meningitis. History of hospitalization for pneumococcal pneumonia within the past 3 years. History of serious systemic infection within the past 12 months. Any of the following treatments to the study eye within 7 days prior to study drug dosing: ranibizumab (Lucentis), bevacizumab (Avastin), pegaptanib (Macugen), or other VEGF inhibitor. Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 90 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |
| Experimental: LFG316: 10 mg/kg (2 doses in cohort 1)<br> | Drug: LFG316<br> <br> |
| Experimental: LFG316: 20 mg/kg (2 doses in cohort 1, 3 doses in cohort 2).<br> | Drug: LFG316<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of anti-vascular endothelial growth factor (anti-VEGF) retreatment vs time | Number of retreatments with anti-VEGF treatments will be recorded. | Day 1 to Day 113 (starting from the day of dosing until the end of the study) | 
| Number and percentage of patients with adverse events. | Adverse events will be determined based on descriptive analyses of vital signs, ECG evaluation, and clinical safety laboratory evaluations. All abnormalities will be flagged and summary statistics will be provided by treatment and visit/time.Will be tabulated by body system and preferred term with a breakdown by treatment. | Day 1 to Day 113 (starting from the day of dosing until the end of the study) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of LFG316 on visual acuity | Early Treatment Diabetic Retinopathy Study (ETDRS best corrected visual acuity measured under ETDRS conditions). Number of letters correctly read will be recorded. | Day 1 to Day 113 | 
| Effect of LFG316 on central retinal thickness, choroidal neovascular membrane area and drusen volume. | summary statistics will be provided by treatment group, cohort and visit/time. Treatment effect will be assessed by comparison of mean change from baseline to Day 85 of patients who received or did not receive anti-VEGF therapy. | Day 1 to Day 113 | 
| Serum concentrations of total LFG316 versus time | Blood samples will be collected. | Days 1, 8, 15, 22, 29, 43, 57, 78, 85 and 113 for both cohorts. | 
| Serum concentration of pharmacodynamic parameters (Weislab and C5) versus time | Blood samples will be collected. | screening and Days 1, 8, 15, 22, 29, 43, 57, 78, 85 and 113 (for both cohorts). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AMD, Age-related Macular Degeneration, Wet AMD, Neovascular AMD