Safety and Efficacy Study of OpRegen for Treatment of Advanced Dry-Form Age-Related Macular Degeneration

Overview

The main objective of the study is evaluation of the safety and tolerability of OpRegen – human embryonic stem cell-derived retinal pigment epithelial (RPE)cells. The study will also include initial exploration of the ability of transplanted OpRegen cells to engraft, survive, and moderate disease progression.

Full Title of Study: “Phase I/IIa Dose Escalation Safety and Efficacy Study of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelium Cells Transplanted Subretinally in Patients With Advanced Dry-Form Age-Related Macular Degeneration (Geographic Atrophy)”

Study Type

  • Study Type: Interventional
  • Study Design
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 2020

Detailed Description

OpRegen® is a cell-based product composed of retinal pigment epithelial (RPE) cells, derived from human embryonic stem cells (hESC) and administered as a cell suspension either in ophthalmic Balanced Salt Solution Plus (BSS Plus) or in CryoStor® 5 (Thaw-and-Inject, TAI).

This is a Phase I/IIa, dose-escalation, evaluating safety and tolerability of OpRegen transplantation to patients with progressive dry-AMD. The study includes also initial exploration of efficacy.

A total of approximately 24 subjects will be enrolled. The subjects should be 50 years of age and older, with non-neovascular (dry) AMD, who have funduscopic findings of GA in the macula, with absence of additional concomitant ocular disorders.

The subjects will be divided into four cohorts, according to their best corrected visual acuity (BCVA) and administered OpRegen dose.

Interventions

  • Biological: OpRegen
    • Targeted dose of 50,000 – 200,000 cells will be delivered into the subretinal space

Arms, Groups and Cohorts

  • Experimental: OpRegen
    • Up to 12 legally blind subjects with best corrected visual acuity of 20/200 or less in first three cohorts and 12 subjects with best corrected visual acuity of 20/64 and 20/250 in fourth cohort

Clinical Trial Outcome Measures

Primary Measures

  • Incidence and frequency of treatment emergent adverse events
    • Time Frame: 12 months post transplantation
    • The AE’s will be graded using NCI’s CTCAE v 3.0
  • Treatment emergent changes of clinical and ophthalmological parameters
    • Time Frame: 12 months post transplantation
    • The parameters will be measured via different modalities, such as vital signs and ocular imaging and captured as adverse events

Secondary Measures

  • Change in GA lesion area
    • Time Frame: 12 months post transplantation
    • Measurement of change in GA lesion area will be performed based on available imaging data by a central reading center.
  • Change in visual acuity
    • Time Frame: 12 months post transplantation
    • Change in visual acuity will be measured by ETDRS chart
  • Change in Quality of Life
    • Time Frame: 12 months post transplantation
    • Change in NEI VFQ-25 Quality of Life score will be measured from baseline

Participating in This Clinical Trial

Inclusion Criteria

1. Age 50 and older;

2. Diagnosis of dry (non-neovascular) age related macular degeneration in both eyes;

3. Funduscopic findings of dry AMD with progressive geographic atrophy in the macula;

4. Best corrected central visual acuity equal or less than 20/200 in cohorts 1-3 and 20/64-20/250 in cohort 4 in the study eye by ETDRS vision testing;

5. Vision in the non-operated eye must be better than or equal to that in the operated eye;

6. Subjects with sufficiently good health to allow participation in all study-related procedures and complete the study follow up period (medical records);

7. Ability to undergo a vitreoretinal surgical procedure under monitored anesthesia care;

8. Blood counts, blood chemistry, coagulation and urinalysis without abnormal significance;

9. Negative for TB (cohort 4), HIV, HBC, and HCV, negative for CMV IgM and EBV IgM;

10. Patients with no history of malignancy (other than a non-melanoma skin cancer). For cancers in remission for more then 5 years enrollment is allowed with concurred documented approval of principal investigator and oncologist prior to enrollment;

11. Willing to defer all future blood and tissue donation;

12. Able to understand and willing to sign informed consent.

Exclusion Criteria

1. Evidence of neovascular AMD by history, as well as by clinical exam, fluorescein angiography (FA), or ocular coherence tomography (OCT) at baseline in either eye;

2. History or presence of diabetic retinopathy, vascular occlusions, uveitis, Coat's disease, glaucoma, cataract or media opacity preventing posterior pole visualization or any significant ocular disease other than AMD that has compromised or could compromise vision in the study eye and confound analysis of the primary outcome;

3. History of retinal detachment repair in the study eye;

4. Axial myopia greater than -6 diopters;

5. At least 2 months following cataract removal in the study eye and Yttrium Aluminum Garnet (YAG) laser capsulotomy in the study eye in the past 4 weeks and any other ocular surgery in the study eye in the past 3 months prior to implantation;

6. History of cognitive impairments or dementia;

7. Contraindication for systemic immunosuppression;

8. History of any condition other than AMD associated with choroidal neovascularization in the study eye (e.g. pathologic myopia or presumed ocular histoplasmosis);

9. Any type of systemic disease or its treatment, in the opinion of the Investigator, including any medical condition (controlled or uncontrolled) that could be expected to progress, recur, or change to such an extent that it may bias the assessment of the clinical status of the patient to a significant degree or put the patient at special risk.

10. Female; pregnancy or breastfeeding;

11. Current participation in another clinical study. Past participation (within 6 months) in any clinical study of a drug administered systemically or to the eye.

12. Currently receiving aspirin, aspirin containing products and/or any other coagulation modifying drugs which cannot be discontinued 7 days prior to surgery;

13. History of cancer (other than a non-melanoma skin cancer). For cancers cured more than five years ago, enrollment is allowed with concurred documented approval of principal investigator and oncologist prior to enrollment.

Gender Eligibility: All

Minimum Age: 50 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • BioTime Inc.
  • Collaborator
    • CellCure Neurosciences Ltd.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Tareq Jaouni, MD, Principal Investigator, Hadassah Ein Kerem University Hospital, Israel
    • Rita Ehrlich, MD, Principal Investigator, Rabin Medical Center, Israel
    • Adiel Barak, MD, Prof., Principal Investigator, Tel Aviv Souraski Medical Center, Israel
    • Richard McDonald, MD, Principal Investigator, West Coast Retina Medical Group, Inc, USA
    • David Boyer, MD, Principal Investigator, Retina Vitreous Associates Medical Group, USA
    • Diana Do, MD, Prof., Principal Investigator, Byers Eye Institute, Stanford, USA
    • David Telander, MD, Principal Investigator, Retinal Consultants Medical Group, USA
  • Overall Contact(s)
    • Ghesal Razag, +1 510 8714125, grazag@biotimeinc.com

References

Idelson M, Alper R, Obolensky A, Ben-Shushan E, Hemo I, Yachimovich-Cohen N, Khaner H, Smith Y, Wiser O, Gropp M, Cohen MA, Even-Ram S, Berman-Zaken Y, Matzrafi L, Rechavi G, Banin E, Reubinoff B. Directed differentiation of human embryonic stem cells into functional retinal pigment epithelium cells. Cell Stem Cell. 2009 Oct 2;5(4):396-408. doi: 10.1016/j.stem.2009.07.002.

Tannenbaum SE, Turetsky TT, Singer O, Aizenman E, Kirshberg S, Ilouz N, Gil Y, Berman-Zaken Y, Perlman TS, Geva N, Levy O, Arbell D, Simon A, Ben-Meir A, Shufaro Y, Laufer N, Reubinoff BE. Derivation of xeno-free and GMP-grade human embryonic stem cells–platforms for future clinical applications. PLoS One. 2012;7(6):e35325. doi: 10.1371/journal.pone.0035325. Epub 2012 Jun 20.

McGill TJ, Bohana-Kashtan O, Stoddard JW, Andrews MD, Pandit N, Rosenberg-Belmaker LR, Wiser O, Matzrafi L, Banin E, Reubinoff B, Netzer N, Irving C. Long-Term Efficacy of GMP Grade Xeno-Free hESC-Derived RPE Cells Following Transplantation. Transl Vis Sci Technol. 2017 Jun 14;6(3):17. doi: 10.1167/tvst.6.3.17. eCollection 2017 Jun.

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