Study to Evaluate Sub-retinal Transplantation of Retinal Pigmented Epithelial Cells in Patients With Dry AMD (PORTRAY)

Ph 2, Double-Masked, Randomized, Parallel, Sham Surgery/Placebo Control, Multi-Center Study to Evaluate Systemic IMT Regimens as Graft Rejection Prophylaxis Following Transplantation of hESC Derived RPE Cells in Patients With AMD

To evaluate the safety of 3 regimens of short-term, low-dose systemic IMT as rejection prophylaxis prior to and/or following transplant of MA09-hRPE cells.

Study Overview

• Status: Withdrawn
• Conditions: Age-Related Macular Degeneration
• Intervention / Treatment: Drug: Placebo tacrolimus and mycophenolate mofetil; Procedure: Sham Surgery; Biological: Sub-retinal transplantation of MA09-hRPE cells; Drug: tacrolimus and mycophenolate mofetil

Detailed Description

This study will be a Phase 2, double-masked, randomized, parallel group, sham surgery/placebo control, multi-center trial. Subjects will be randomized in a 3:1 ratio to either the treatment or control group respectively. Subjects randomized to the treatment group will receive transplantation with 200,000 MA09-hRPE (human embryonic stem cell derived retinal pigmented epithelial)cells in one eye. Subjects randomized to the control group will have a sham surgery without transplantation of MA09-hRPE cells. The study eye must meet all eligibility criteria. If both eyes meet all eligibility criteria, then the study eye will be the eye with the worst Best Corrected Visual Acuity (BCVA) score at screening. If both eyes have identical BCVA scores, then the study eye will be chosen by the Investigator and the subject. There will be 3 cohorts, each with a different regimen of low-dose IMT [tacrolimus and mycophenolate mofetil (MMF)]. Subjects will be randomized to treatment or control within cohorts, defined by severity of BCVA in the study eye at Screening. Enrollment in Cohort 1 and 2 will be concurrent. Enrollment into Cohort 3 will begin once Cohort 2 is fully enrolled.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Wills Eye Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Geographic atrophy (GA) secondary to AMD with no evidence of prior to active choroidal neovascularization (CNV) in the study eye.
• BCVA in the study eye must be between 4 and 58 Early Treatment of Diabetic Retinopathy Study (EDTRS) letters (20/800 to 20/80; 0.025-0.25)
• Subjects must be willing to take IMT and willing to discontinue any medication that has a known strong interaction with tacrolimus or mycophenolate mofetil (MMF)

Exclusion Criteria:

• Macular atrophy due to causes other than AMD
• Other sight-threatening ocular disease
• Current or prior history of optic neuropathy, retinal dystrophy, retinitis pigmentosa, chorioretinitis, vasoocclusive disease, retinal vascular disease or retinal degenerative disease OTHER than AMD
• History of uveitis
• History of allergic reaction to sulfa drugs
• Solid organ or bone marrow transplant recipient
• History of malignancy within the previous 5 years (except for BCC (basal cell carcinoma), SCC (squamous cell carcinoma) or in-situ cervical)
• History of myocardial infarction with past 12 months
• History of clinically significant cardiac dysrhythmia
• History of diabetes mellitus, bowel disease, tuberculosis
• Prior treatment for non-exudative AMD
• Intraocular, refractive or cataract surgery in the last 12 weeks
• Prior retinal surgery, vitrectomy, macular laser photocoagulation, external beam radiation therapy, transpupillary thermotherapy, glaucoma filtration surgery or corneal surgery (except cataract surgery)
• Receipt of gene transfer of cell transplant therapy in a prior clinical trial
• Participation in any other interventional clinical trial within the last 12 weeks

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Control group; Sham surgery and placebo immunosuppressive therapy (IMT)	Drug: Placebo tacrolimus and mycophenolate mofetil; placebo; Procedure: Sham Surgery; Sham surgery
Active Comparator: Active Group; Sub-retinal transplantation of MA09-hRPE cells and IMT	Biological: Sub-retinal transplantation of MA09-hRPE cells; transplantation; Drug: tacrolimus and mycophenolate mofetil; Immunosuppressive Agents

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of subjects with evidence of graft failure or rejection.	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in area of geographic atrophy by Optical coherence tomography	Change from baseline to Week 78	18 months
Change in area of geographic atrophy by Autofluorescence	Change from baseline to Week 78	18 months
Change in average Best Corrected Visual Acuity (BCVA)	Change from baseline to Week 78	18 months

Collaborators and Investigators

• Sponsor: Astellas Institute for Regenerative Medicine

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2015
• Primary Completion (Actual): May 5, 2017
• Study Completion (Actual): May 5, 2017

Study Registration Dates

• First Submitted: September 21, 2015
• First Submitted That Met QC Criteria: September 29, 2015
• First Posted (Estimate): September 30, 2015

Study Record Updates

• Last Update Posted (Actual): July 26, 2017
• Last Update Submitted That Met QC Criteria: July 25, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Calcineurin Inhibitors; Tacrolimus; Mycophenolic Acid
• Other Study ID Numbers: 7317-CL-0002; MA09-hRPE AMD 02 PORTRAY (Other Identifier: Sponsor)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided