iSONEP to Treat Persistent Pigment Epithelial Detachment (PED) in Subjects With Exudative Age-Related Macular Degeneration (AMD) or Polypoidal Choroidal Vasculopathy (PCV)

Study Overview
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Brief Summary
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LT1009-Oph-002 is a Phase 1b study designed to evaluate the safety and potential efficacy of iSONEP following one, two or three injections of iSONEP, as needed, for the treatment of Pigment Epithelial Detachment (PED) secondary to PED Secondary to Exudative Age-Related Macular Degeneration (AMD) or Polypoidal Choroidal Vasculopathy (PCV).

Detailed Description
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Sixteen (16) subjects per dose group who have received a minimum of 3 and no more than 7 doses of an anti-VEGF agent (i.e., Lucentis or Avastin), and whose PED has not decreased by greater than 25% in height despite therapy, will be enrolled for a total of 32 subjects. The presence of PED diagnosed by the Investigator will be confirmed by SDOCT, ICG and FA by a digital imaging reading center prior to subject enrollment. The ability of iSONEP to induce regression of persistent PED in subjects with exudative AMD or PCV despite previous treatment with an anti-VEGF agent will be evaluated.

Official Title
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A Phase 1b Multi-Center, Open-Label and Randomized Study of iSONEP (Sonepcizumab/LT1009) Administered as Intravitreous Injections to Subjects With PED Secondary to Exudative Age-Related Macular Degeneration or Polypoidal Choroidal Vasculopathy

Conditions
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Pigment Epithelial Detachment

Intervention / Treatment
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* Drug: iSONEP (sonepcizumab/LT1009)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females > 50 years of age with a diagnosis of PED secondary to AMD or PCV Serous and/or fibrovascular PED secondary to exudative AMD or secondary to PCV (confirmed by SDOCT, FA and ICG) that has not demonstrated at least a 25% decrease in the height of the PED (from the onset of anti-VEGF therapy) following a minimum of 3 doses of an anti-VEGF agent (i.e., Lucentis or Avastin) PED that has a height greater than 100 μm Presence of CNV secondary to (i) AMD (based on FA) or (ii) PCV (based on ICG) ETDRS BCVA of 20/32 to 20/320 (letter score of 73 to 25) in the study eye ETDRS visual acuity of 20/400 or better in the fellow eye Exclusion Criteria: Subjects previously treated with, or are currently receiving treatment with another investigational agent or device for neovascular AMD in the study eye Subjects who have received < 3 and > 7 anti-VEGF treatments in the study eye Subjects with retinal angiomatous proliferation (RAP lesion) Lucentis or Avastin within 30 days prior to Day 1 in the study eye

Ages Eligible for Study
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Minimum Age: 50 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.5 mg of iSONEP (sonepcizumab/LT1009)<br>iSONEP (sonepcizumab/LT1009) is a humanized murine monoclonal antibody to sphingosine 1-phosphate | Drug: iSONEP (sonepcizumab/LT1009)<br>* Up to 3 doses of iSONEP given monthly will be administered as intravitreous injections in the ophthalmologist's office.<br>|
| Experimental: 2.0 mg of iSONEP (sonepcizumab/LT1009)<br>iSONEP (sonepcizumab/LT1009) is a humanized murine monoclonal antibody to sphingosine 1-phosphate | Drug: iSONEP (sonepcizumab/LT1009)<br>* Up to 3 doses of iSONEP given monthly will be administered as intravitreous injections in the ophthalmologist's office.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate safety and tolerability following one, two or three intravitreous injections of iSONEP | The number of participants with adverse events; changes in electrocardiogram parameters, diastolic and systolic blood pressure, pulse, temperature and intraocular pressure from baseline to the end of the study. | 8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate various efficacy outcomes throughout the study | Changes in subretinal and intraretinal fluid, in retinal thickness and in size and height of PED compared with baseline at Days 30, 45, 60 and 90 Changes in CNV lesion area from baseline Time course to regression of PED; proportion of subjects with complete resolution of PED following a single, second or third IVT iSONEP injection Changes in VA; proportion of eyes gaining > or = 0, 5, 10 and 15 letters on ETDRS Proportion of subjects with an improvement from baseline in VFQ-25 overall composite score to Day 60, Month 4 and Month 8 Time to re-treatment with anti-VEGF therapy | 8 months | 
| To evaluate the immunogenicity (antibody response) of iSONEP following multiple intravitreous injections | Production and/or changes in antibody concentration to iSONEP from baseline to the end of the study | 8 months | 
| To characterize the systemic pharmacokinetic profile of iSONEP | For the 2.0 mg dose of iSONEP Maximum plasma concentration Area under the concentration versus time curve Terminal half-life Terminal elimination constant Time of maximum concentration | 8 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pigment epithelial detachment, Exudative age-related macular degeneration, Polypoidal choroidal vasculopathy