A Study Of Implantation Of Retinal Pigment Epithelium In Subjects With Acute Wet Age Related Macular Degeneration

Study Overview
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Brief Summary
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Phase 1 trial of retinal pigment epithelium replacement in subjects with wet age-related macular degeneration in whom there is rapidly progressing vision loss

Detailed Description
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Phase 1, open-label, safety and feasibility study of implantation of PF-05206388 (human embryonic stem cell derived retinal pigment epithelium) in subjects with wet age related macular degeneration and rapid vision loss

Official Title
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Phase 1, Open-label, Safety and Feasibility Study of Implantation of Pf-05206388 (Human Embryonic Stem Cell Derived Retinal Pigment Epithelium (Rpe) Living Tissue Equivalent) in Subjects With Acute Wet Age Related Macular Degeneration and Recent Rapid Vision Decline

Conditions
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Age Related Macular Degeneration

Intervention / Treatment
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* Biological: PF-05206388


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and /or post-menopausal female subjects aged 60 years or above. Diagnosis of wet Age-related Macular Degeneration (AMD) plus rapid recent vision decline An informed consent document signed and dated by the subject or a legal representative. Exclusion Criteria: Pregnant females; breastfeeding females; and females of childbearing potential. Treatment with an investigational drug within 30 days (or as determined by the local requirement, whichever is longer) or 5 half-lives preceding the first dose of study medication. Current or previous significant other ocular disease in the study eye, as determined by the investigator.

Ages Eligible for Study
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Minimum Age: 60 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>PF-05206388 Retinal Pigment Epithelium living tissue equivalent for intraocular use in the form of a monolayer of Retinal Pigmented Epithelial (RPE) cells immobilized on a polyester membrane | Biological: PF-05206388<br>* PF-05206388 will be provided as a Retinal Pigment Epithelium living tissue equivalent for intraocular use in the form of a monolayer of Retinal Pigmented Epithelial (RPE) cells immobilized on a polyester membrane. The membrane is approximately 6 mm x 3 mm and will contain a confluent layer of RPE cells, at a nominal dose of 17 mm2. The implant is intended to be life-long.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events. | The number of Adverse Events (AE) and Serious Adverse Events (SAE) noted during the study and an assessment of whether they are trial product related | 52 weeks | 
| Change in baseline in ETDRS best corrected visual acuity (BCVA) - Proportion of subjects with an improvement of 15 letters or more at Week 24. | The number of patients with a difference between the baseline BCVA and BCVA at 24 weeks in ETDRS letters, where the differences is 15 letters or more, as a percentage of the total number of cases. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in baseline in ETDRS best corrected visual acuity (BCVA) - Proportion of subjects with an improvement of 15 letters or more | The number of patients with a difference between the baseline BCVA and BCVA at weeks 1,2,4,8, 12,16, 36, 52 in ETDRS letters, where the differences is 15 letters or more, as a percentage of the total number of cases. | Weeks 1,2,4,8, 12,16, 36, 52 | 
| Mean change of best corrected visual acuity (BCVA) from baseline by study visit. | The mean difference between the baseline BCVA and final BCVA in ETDRS letters for all cases | 52 weeks | 
| Position of PF-05206388 by serial biomicroscopic evaluation. | Measurement of movement in millimetre and rotation in degrees measure relative to baseline, at day 2 and weeks 1, 2, 4, 8, 10, 12, 16, 24, 36 and 52 | Day 2 and Weeks 1, 2, 4, 8, 10, 12, 16, 24, 36, 52 | 
| Position and presence of pigmented RPE cells by serial fundus photography | The subjective reporting of area of pigmentation as a % with cross reference to the OCT at weeks 2, 4, 8, 10, 12, 16, 24, 36 and 52 | Weeks 2, 4, 8, 10, 12, 16, 24, 36, 52 | 
| Mean change from baseline in contrast sensitivity by Pelli Robson test | The mean difference between the baseline BCVA and final BCVA in Pelli Robson letters read, across all subjects | Weeks 24, 52 | 
| Change in liver and renal function by blood tests and liver ultrasound . | Record of any abnormalities in liver and renal function on blood testing and any abnormalities detected on the liver ultrasound. | Weeks 24 and 52 | 
| Change in leakage or perfusion in normal fundal vasculature and presence of abnormal vasculature by fundus fluorescein angiography. | Assessment and noting of abnormalities on Funded fluorescine angiography at weeks 4, 8, 12, 24 and 52. | Weeks 4, 8, 12, 24 and 52 | 
| Change in central 30 degree of visual function by Humphrey Field test. | Recording and reporting of any changes on the central 30 degree field on the automated Humphrey Field test at weeks 4, 8, 12, 24 and 52 | Weeks 4, 8, 12, 24 and 52 | 
| Change in thickness of RPE layer by B-mode orbital ultrasound. | Recording of any changes in thickness of RPE layer by B-mode orbital ultrasound carried out by the ocular oncologist or medical physicist at weeks 4, 8, 16, 24, 36, 52. | Weeks 4, 8, 16, 24, 36, 52 |