Study of Subretinal Implantation of Human Embryonic Stem Cell-Derived RPE Cells in Advanced Dry AMD
Primary Purpose
Dry Macular Degeneration, Geographic Atrophy
Status
Unknown status
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CPCB-RPE1
Sponsored by
About this trial
This is an interventional other trial for Dry Macular Degeneration
Eligibility Criteria
Inclusion Criteria:
- Patients able to understand and willing to sign the informed consent
- Adult male or female patients with the age of 55 to 85 (inclusive) years who are not employees of the trial sites
- In sufficiently good health to reasonably expect survival for at least five years after treatment
- Clinical findings consistent with advanced dry AMD with evidence of one or more areas of ≥1.25 square millimeter of geographic atrophy involving the central fovea
- Geographic atrophy defined as attenuation or loss of RPE as observed by biomicroscopy, OCT, or FAF
- The best-corrected visual acuity (BCVA) of the eye to receive the implant will be equal or worse than 20/200 in the first half of the study patients and between 20/80 and 20/400 (inclusive) in the second half of the patients. The BCVA of the eye that is NOT to receive the implant will be better or equal to the eye that will receive the implant
- Medically suitable to undergo pars plana vitrectomy and the surgical implant procedure, including being able to position post-operatively and use post-operative medications as required
- Medically suitable for general anesthesia or monitored intravenous sedation, if needed
- Patients who are pseudophakic or aphakic in the study eye
- If designated as an organ donor, willing to forego live organ donation
- Willing to consent to the post-mortem removal of the implant from the treated eye for the sponsor's analysis. The patient may also elect to donate the implanted and fellow, untreated eye, for histological analysis.
- Able to understand the requirements of the study and willing and able to participate in long term follow up.
Exclusion Criteria:
- Presence of active or inactive choroidal neovascularization (CNV)
- Presence or history of retinal dystrophy, retinitis pigmentosa, chorioretinitis, central serous choroidopathy or any other inflammatory ocular disease except dry eye syndrome
- Presence or history of severe, end-stage corneal dystrophy
- History of steroid induced ocular hypertension or glaucoma
- Presence of moderate to severe glaucomatous optic neuropathy in the study eye, uncontrolled IOP, use of two or more topical agents to control intraocular pressure; history of glaucoma-filtering surgery
- Presence of moderate to severe non-proliferative diabetic retinopathy in the study eye
- Presence of any proliferative diabetic retinopathy in the study eye
- Presence of uncontrolled diabetes mellitus (HbA1c > 8) at the time of screening
- History of retinal detachment or retinal detachment repair in the study eye other than peripheral retinal tears or holes treated exclusively with laser or cryotherapy
- Presence of any other sight-threatening ocular disease
- History of cognitive impairments or dementia which may impact the patient's ability to participate in the informed consent process and to appropriately complete evaluations
- History of any immunodeficiency
- Evidence of herpetic or other viral eye disease
- Any current use of immunosuppressive therapy other than intermittent or low dose corticosteroids
- Participation within previous 3 months in any clinical trial of a drug by ocular or systemic administration (within previous 18 months for sustained release products)
- Axial myopia of greater than -8 diopters in the eye that is to be implanted
- Axial length greater than 28 mm in the eye that is to be implanted
- History of malignancy within the past 5 years (with the exception of successfully treated [excised] basal cell carcinoma [skin cancer] or successfully treated squamous cell carcinoma of the skin)
- History of myocardial infarction in previous 12 months
- Alanine transaminase/aspartate aminotransferase (ALT/AST) >3.0 times the upper limit of normal or any known liver disease
- Renal insufficiency, as defined by estimated creatinine clearance of < 45 ml/min
- A positive (or "reactive") test for HIV, or Hepatitis B, or Hepatitis C
- A hemoglobin concentration of less than 10 gm/dl, a platelet count of less than 100K/µL or an absolute neutrophil count of less than 1000/µL at study entry
- Ocular lens removal within the previous 6 weeks in either eye
- Any other ocular surgery in the study eye in the previous 3 months
- If female, pregnancy, the wish to become pregnant, or lactation
- Any other medical condition, which, in the Investigator's judgment, will interfere with the patient's ability to comply with the protocol, compromises patient safety, or interferes with the interpretation of the study results
Sites / Locations
- Retinal Consultants of Arizona LTD
- Retina-Vitreous Associates Medical Group
- USC Keck School of Medicine / Eye Institute
- Southern California Desert Retina Consultants
- Orange County Retina Medical Group
- California Retina Consultants
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
CPCB-RPE1 treatment
Arm Description
Subretinal implantation of CPCB-RPE1 in dry AMD patients
Outcomes
Primary Outcome Measures
Frequency and Severity of Treatment-Related Adverse Events [Safety and Tolerability]
Comparison of product, procedure and immunosuppression related adverse events in the implanted eye to those experienced in the non-treated eye
Secondary Outcome Measures
Visual Acuity
Comparison of VA changes in the treated eye versus baseline and versus the non-treated eye
Visual Field
Comparison of visual field changes in the treated eye versus baseline and versus the non-treated eye
Photoreceptor Electrical Responses
Comparison of multifocal electroretinogram changes in the treated eye versus baseline and versus the non-treated eye
Full Information
NCT ID
NCT02590692
First Posted
October 23, 2015
Last Updated
May 27, 2020
Sponsor
Regenerative Patch Technologies, LLC
1. Study Identification
Unique Protocol Identification Number
NCT02590692
Brief Title
Study of Subretinal Implantation of Human Embryonic Stem Cell-Derived RPE Cells in Advanced Dry AMD
Official Title
A Phase I/IIa Safety Study of Subretinal Implantation of CPCB-RPE1 (Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells Seeded on a Polymeric Substrate) in Subjects With Advanced, Dry Age-Related Macular Degeneration (AMD)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2020
Overall Recruitment Status
Unknown status
Study Start Date
February 16, 2016 (Actual)
Primary Completion Date
July 2019 (Actual)
Study Completion Date
June 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Regenerative Patch Technologies, LLC
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The Phase I/IIa clinical trial is designed to assess the feasibility of delivery and safety of Human Embryonic Stem Cell-Derived RPE Cells on a parylene membrane (CPCB-RPE1) in patients with advanced, dry age-related macular degeneration.
Primary Objective:
• To test the safety and tolerability of CPCB-RPE1 during and after subretinal implantation in patients with geographic atrophy with evidence of involvement of the central fovea.
Secondary Objective:
• To assess visual acuity, visual field, and retinal function after CPCB-RPE1 implantation. Implanted and fellow eyes will be compared post-implantation to assess the ability of the implant to prevent disease progression.
Exploratory Objectives:
• To assess the feasibility of measuring the change in area of geographic atrophy over time using spectral domain optical coherence tomography or fundus autofluorescence.
Detailed Description
The study will include two cohorts, each of 10 patients. For the first cohort, the study population will be patients with advanced, dry AMD with evidence of significant geographic atrophy involving the fovea. These patients will have significant central vision loss with best-corrected visual acuity (BCVA) of the eye to be implanted of BCVA of 20/200 or worse. Each of these patients will have substantial RPE and photoreceptor loss. Patients will be screened for overall health status to minimize risks associated with retinal surgery and any subsequent immunosuppression.
As the safety and tolerability of CPCB-RPE1 is demonstrated in the first cohort, patients with less advanced disease will be recruited into a second cohort in this Phase I/IIa clinical trial. In this second cohort patients will have significant central vision loss with BCVA of the eye to be implanted of 20/80 or worse, but better than or equal to 20/400 with comparably less damage to the RPE/photoreceptor complex than Cohort 1. These patients will be screened in the same manner for overall health status to minimize risks associated with retinal surgery and any subsequent immunosuppression. Assessments of visual function will be the same as in Cohort 1.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dry Macular Degeneration, Geographic Atrophy
7. Study Design
Primary Purpose
Other
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CPCB-RPE1 treatment
Arm Type
Experimental
Arm Description
Subretinal implantation of CPCB-RPE1 in dry AMD patients
Intervention Type
Biological
Intervention Name(s)
CPCB-RPE1
Intervention Description
Patients will receive one CPCB-RPE1 implant of approximately 100,000 differentiated RPE cells attached to a small parylene membrane. The density of cells on the membrane represents the approximate density of RPE cells in the human eye. The membrane size was chosen to cover a substantial portion of the macular region of the retina.
Primary Outcome Measure Information:
Title
Frequency and Severity of Treatment-Related Adverse Events [Safety and Tolerability]
Description
Comparison of product, procedure and immunosuppression related adverse events in the implanted eye to those experienced in the non-treated eye
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Visual Acuity
Description
Comparison of VA changes in the treated eye versus baseline and versus the non-treated eye
Time Frame
1 year
Title
Visual Field
Description
Comparison of visual field changes in the treated eye versus baseline and versus the non-treated eye
Time Frame
1 year
Title
Photoreceptor Electrical Responses
Description
Comparison of multifocal electroretinogram changes in the treated eye versus baseline and versus the non-treated eye
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
55 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients able to understand and willing to sign the informed consent
Adult male or female patients with the age of 55 to 85 (inclusive) years who are not employees of the trial sites
In sufficiently good health to reasonably expect survival for at least five years after treatment
Clinical findings consistent with advanced dry AMD with evidence of one or more areas of ≥1.25 square millimeter of geographic atrophy involving the central fovea
Geographic atrophy defined as attenuation or loss of RPE as observed by biomicroscopy, OCT, or FAF
The best-corrected visual acuity (BCVA) of the eye to receive the implant will be equal or worse than 20/200 in the first half of the study patients and between 20/80 and 20/400 (inclusive) in the second half of the patients. The BCVA of the eye that is NOT to receive the implant will be better or equal to the eye that will receive the implant
Medically suitable to undergo pars plana vitrectomy and the surgical implant procedure, including being able to position post-operatively and use post-operative medications as required
Medically suitable for general anesthesia or monitored intravenous sedation, if needed
Patients who are pseudophakic or aphakic in the study eye
If designated as an organ donor, willing to forego live organ donation
Willing to consent to the post-mortem removal of the implant from the treated eye for the sponsor's analysis. The patient may also elect to donate the implanted and fellow, untreated eye, for histological analysis.
Able to understand the requirements of the study and willing and able to participate in long term follow up.
Exclusion Criteria:
Presence of active or inactive choroidal neovascularization (CNV)
Presence or history of retinal dystrophy, retinitis pigmentosa, chorioretinitis, central serous choroidopathy or any other inflammatory ocular disease except dry eye syndrome
Presence or history of severe, end-stage corneal dystrophy
History of steroid induced ocular hypertension or glaucoma
Presence of moderate to severe glaucomatous optic neuropathy in the study eye, uncontrolled IOP, use of two or more topical agents to control intraocular pressure; history of glaucoma-filtering surgery
Presence of moderate to severe non-proliferative diabetic retinopathy in the study eye
Presence of any proliferative diabetic retinopathy in the study eye
Presence of uncontrolled diabetes mellitus (HbA1c > 8) at the time of screening
History of retinal detachment or retinal detachment repair in the study eye other than peripheral retinal tears or holes treated exclusively with laser or cryotherapy
Presence of any other sight-threatening ocular disease
History of cognitive impairments or dementia which may impact the patient's ability to participate in the informed consent process and to appropriately complete evaluations
History of any immunodeficiency
Evidence of herpetic or other viral eye disease
Any current use of immunosuppressive therapy other than intermittent or low dose corticosteroids
Participation within previous 3 months in any clinical trial of a drug by ocular or systemic administration (within previous 18 months for sustained release products)
Axial myopia of greater than -8 diopters in the eye that is to be implanted
Axial length greater than 28 mm in the eye that is to be implanted
History of malignancy within the past 5 years (with the exception of successfully treated [excised] basal cell carcinoma [skin cancer] or successfully treated squamous cell carcinoma of the skin)
History of myocardial infarction in previous 12 months
Alanine transaminase/aspartate aminotransferase (ALT/AST) >3.0 times the upper limit of normal or any known liver disease
Renal insufficiency, as defined by estimated creatinine clearance of < 45 ml/min
A positive (or "reactive") test for HIV, or Hepatitis B, or Hepatitis C
A hemoglobin concentration of less than 10 gm/dl, a platelet count of less than 100K/µL or an absolute neutrophil count of less than 1000/µL at study entry
Ocular lens removal within the previous 6 weeks in either eye
Any other ocular surgery in the study eye in the previous 3 months
If female, pregnancy, the wish to become pregnant, or lactation
Any other medical condition, which, in the Investigator's judgment, will interfere with the patient's ability to comply with the protocol, compromises patient safety, or interferes with the interpretation of the study results
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jane Lebkowski, Ph.D.
Organizational Affiliation
Regenerative Patch Technologies
Official's Role
Study Director
Facility Information:
Facility Name
Retinal Consultants of Arizona LTD
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85053
Country
United States
Facility Name
Retina-Vitreous Associates Medical Group
City
Beverly Hills
State/Province
California
ZIP/Postal Code
90211
Country
United States
Facility Name
USC Keck School of Medicine / Eye Institute
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Southern California Desert Retina Consultants
City
Palm Desert
State/Province
California
ZIP/Postal Code
92211
Country
United States
Facility Name
Orange County Retina Medical Group
City
Santa Ana
State/Province
California
ZIP/Postal Code
92705
Country
United States
Facility Name
California Retina Consultants
City
Santa Barbara
State/Province
California
ZIP/Postal Code
93103
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Study of Subretinal Implantation of Human Embryonic Stem Cell-Derived RPE Cells in Advanced Dry AMD
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