Myopic Macular DegenerationPhase 1/2NCT02122159
Research With Retinal Cells Derived From Stem Cells for Myopic Macular Degeneration
A Phase 1/2 study testing MA09-hRPE Cellular Therapy in people with Myopic Macular Degeneration, run by University of California, Los Angeles.
Trial summary
Pathologic myopia is a major cause of legal blindness worldwide. In myopic macular degeneration (MMD), there is degeneration of the retinal pigment epithelial (RPE) layer, and associated photoreceptors, resulting in vision loss. There is currently no standard treatment for MMD. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Myopic Macular Degeneration
- What is being tested?
- MA09-hRPE Cellular Therapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Mar 2013to Jul 2016
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult male or female over 40 years of age.
- Patient should be in sufficiently good health to reasonably expect survival for at least four years after treatment
- Axial myopia of equal to or greater than -8 diopters and/or axial length equal to or greater than 28 mm
- Clinical findings consistent with MMD with evidence of one or more areas of >250microns of geographic atrophy (as defined in the Age-Related eye Disease Study [AREDS] study) involving the central fovea.
- GA defined as attenuation or loss of RPE as observed by biomicroscopy, OCT, and FA.
- No evidence of current or prior choroidal neovascularization
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- The visual acuity of the eye to receive the transplant will be no better than 20/80.
- The visual acuity of the eye that is NOT to receive the transplant will be no worse than 20/400.
- The eye with the more advanced disease and worse vision will be the study eye.
- Electrophysiological findings consistent with macula-involving geographic atrophy.
- Medically suitable to undergo vitrectomy and subretinal injection.
- Medically suitable for general anesthesia or waking sedation, if needed.
- Medically suitable for transplantation of an embryonic stem cell line:
- Any laboratory value, which falls slightly outside of the normal range, will be reviewed by the Medical Monitor and Investigators to determine its clinical significance. If it is determined not to be clinically significant, the patient may be enrolled into the study.
- Normal serum chemistry (sequential multi-channel analyzer 20 [SMA-20]) and hematology (complete blood count [CBC], prothrombin time [PT], and activated partial thromboplastin time [aPTT]) screening tests. (NOTE:With the exception of abnormalities specifically identified in the exclusion criteria)
- Negative urine screen for drugs of abuse.
- Negative human immunodeficiency virus (HIV), hepatitis B (HBV), hepatitis C (HCV) serologies.
- No history of malignancy (with the exception of successfully treated (excised) basal cell carcinoma[skin cancer] or successfully treated squamous cell carcinoma of the skin).
- Negative cancer screening within previous 6 months:
- complete history \& physical examination;
- dermatological screening exam for malignant lesions;
- negative fecal occult blood test \& negative colonoscopy within previous 7 years;
- negative chest roentgenogram (CXR);
- normal CBC \& manual differential;
- negative urinalysis (U/A);
- normal thyroid exam;
- if male, normal testicular examination; digital rectal examination (DRE) and prostate specific antigen (PSA);
- if female, normal pelvic examination with Papanicolaou smear; and
- If female, normal clinical breast exam and, negative mammogram.
- If female and of childbearing potential, willing to use two effective forms of birth control during the study.
- If male, willing to use barrier and spermicidal contraception during the study.
- Willing to defer all future blood, blood component or tissue donation.
- Able to understand and willing to sign the informed consent.
Who cannot join
- Presence of active or inactive CNV.
- Presence of a posterior staphyloma.
- Presence or history of retinal dystrophy, retinitis pigmentosa, chorioretinitis, central serious choroidopathy, diabetic retinopathy or other retinal vascular or degenerative disease (i.e. AMD) other than MMD.
- History of optic neuropathy.
- Macular atrophy due to causes other than MMD.
- Presence of glaucomatous optic neuropathy in the study eye, uncontrolled IOP, or use of two or more agents to control IOP (acetazolamide, beta blocker, alpha-1-agonist, antprostaglandins, carbonic anhydrase inhibitors).
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- Cataract of sufficient severity likely to necessitate surgical extraction within 1 year.
- History of retinal detachment repair in the study eye.
- History of malignancy (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.
- History of cognitive impairments or dementia which may impact the patients ability participate in the informed consent process and to appropriately complete evaluations.
- Any immunodeficiency.
- Any current immunosuppressive therapy other than intermittent or low dose corticosteroids.
- Alanine transaminase/aspartate aminotransferase (ALT/AST) >1.5 times the upper limit of normal or any known liver disease.
- Renal insufficiency, as defined by creatinine level >1.3 mg/dL.
- A hemoglobin concentration of less than 10gm/dL, a platelet count of less than 100k/mm3 or an absolute neutrophil count of less than 1000/mm3 at study entry.
- Serologic evidence of infection with Hepatitis B, Hepatitis C, or HIV.
- Current participation in any other clinical trial.
- Participation within previous 6 months in any clinical trial of a drug by ocular or systemic administration.
- Any other sight-threatening ocular disease.
- Any history of retinal vascular disease (compromised blood-retinal barrier.
- Glaucoma.
- Uveitis or other intraocular inflammatory disease.
- Significant lens opacities or other media opacity.
- Ocular lens removal within previous 3 months.
- Ocular surgery in the study eye in the previous 3 months
- If female, pregnancy 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.
About this study
Official title: A Phase I/II, Open-Label, Prospective Study to Determine the Safety and Tolerability of Sub-retinal Transplantation of Human Embryonic Stem Cell Derived Retinal Pigmented Epithelial (MA09-hRPE) Cells in Patients With Geographic Atrophy Secondary to Myopic Macular Degeneration
Pathologic myopia is a major cause of legal blindness worldwide. In myopic macular degeneration (MMD), there is degeneration of the retinal pigment epithelial (RPE) layer, and associated photoreceptors, resulting in vision loss. There is currently no standard treatment for MMD.
Transplantation of intact sheets of RPE and suspensions of isolated individual RPE cells as well as autologous translocation of RPE cells has been attempted as treatment for AMD. Human photoreceptors are comprised of two cell types-rods and cones. Both have a close relationship with the outermost retinal cells, the retinal pigmented epithelium (RPE). The RPE is located between the choroid and the photoreceptors. The RPE maintains photoreceptor function by recycling photopigments,delivering, metabolizing and storing vitamin A, phagocytosing rod photoreceptor outer segments, transporting iron and small molecules between retina and choroid, maintaining Bruch's membrane and absorbing stray light to allow better image resolution. In essence, the RPE layer is critical to the function and health of photoreceptors and the retina as a whole.
Read more
Human PRE (hRPE) transplantation may be a viable option for treatment of degenerative diseases of the retina.
MA09-hRPE cells are fully differentiated human RPE cells derived from embryonic stem cells. Transplanted hRPE cells prepared by Advanced Cell Technology have been studied in rodent models of macular degenerative disease. The data suggests that the subretinal injection of ACT's hRPE cell products rescues, or at least delays, loss of visual function in two animal models of retinal degenerative diseases.
The main purpose of this study is to evaluate the safety and tolerability of MA09-hRPE cellular therapy in patients with Myopic Macular Degeneration (MMD). Another objective is to evaluate potential efficacy endpoints to be used in future studies of RPE cellular therapy.
- Conditions
- Myopic Macular Degeneration
- Being tested
- MA09-hRPE Cellular Therapy
- Keywords
- safety, tolerability, RPE cellular therapy, MMD
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MA09-hRPE Cellular TherapyBiological
A suspension of either 50,000 MA09-hRPE cells (first cohort), 100,000 MA09-hRPE cells (second cohort), 150,000 MA09-hRPE cells (third cohort) or 200,000 MA09-hRPE cells (fourth cohort) in 150 uL of BSS plus will be implanted over 1 minute in the space created.
| Study group | Role | What they receive |
|---|---|---|
| MA09-hRPE Cellular Therapy | Experimental | MA09-hRPE cells for transplantation will be provided by Ocata Therapeutics as a suspension frozen to the temperature of liquid nitrogen (approximately -196 °C). They will be processed at UCLA under GMPs according to protocol. Following vitrectomy performed under general anesthesia or waking sedation at the surgeon's discretion, hRPE cells will be introduced into a subretinal bleb formed by the injection of balanced salt solution (BSS). Direct viewing will guide the implantation of thawed and washed MA09-hRPE cells, resuspended in BSS, into the created bleb over a period of one minute. To avoid cell reflux, the cannula used to introduce the cells will be held in position for an additional minute. A suspension of either 50,000 MA09-hRPE cells (first cohort), 100,000 MA09-hRPE cells (second cohort), 150,000 MA09-hRPE cells (third cohort) or 200,000 MA09-hRPE cells (fourth cohort) in 150 uL of BSS plus will be implanted over 1 minute in the space created. Receives: Biological: MA09-hRPE Cellular Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of hESC-derived RPE cells
The transplantation of hESC-derived RPE cells MA09-hRPE will be considered safe and tolerated in the absence of:
- Any grade 2 (NCI grading system) or greater adverse event related to the cell product
- Any evidence that the cells are contaminated with an infectious agent
- Any evidence that the cells show tumorigenic potential
Measured: 12 months
Secondary outcomes (2)
Evidence of successful engraftment
Evidence of successful engraftment will consist of:
- Structural evidence (OCT imaging, fluorescein angiography, slit-lamp examination with fundus photography) that cells have been implanted in the correct location
- Electroretinographic evidence (mfERG) showing enhanced activity in the implant location
Measured: 12 months
Evidence of rejection
Evidence of rejection will consist of:
- Structural (imaging) evidence that implanted MA09-hRPE cells are no longer in the correct location or the presence of vascular leakage
If enhanced electroretinographic activity is observed after the transplantation, subsequent electroretinographic evidence that activity has returned to pre-transplant conditions may be an indication of graft rejection
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2014 (estimated)
- Study startMar 2013
- Primary completionJul 2016
- Study completionJul 2016
Why it stopped: Study to be revised. Future plans to be determined.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myopic Macular DegenerationStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Collaborators
- Ocata Therapeutics
- Responsible party
- Principal investigator, Steven Schwartz, University of California, Los Angeles
- Investigators
- Steven Schwartz, MD, Principal investigator, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02122159
- Sponsor's protocol ID
- JSEI MA09-hRPE MMD
- Status last verified
- Jul 2016
- First submitted
- 1 Apr 2014
- Last updated
- 18 Jul 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II, Open-Label, Prospective Study to Determine the Safety and Tolerability of Sub-retinal Transplantation of Human Embryonic Stem Cell Derived Retinal Pigmented Epithelial (MA09-hRPE) Cells in Patients With Geographic Atrophy Secondary to Myopic Macular Degeneration
- ClinicalTrials.gov ID
- NCT02122159
- Acronym / sponsor ID
- JSEI MA09-hRPE MMD
- Conditions
- Myopic Macular Degeneration
- Keywords
- safety, tolerability, RPE cellular therapy, MMD
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study to be revised. Future plans to be determined.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Collaborators
- Ocata Therapeutics
- Study start
- Mar 2013
- Primary completion
- Jul 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 24 Apr 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Pathologic myopia is a major cause of legal blindness worldwide. In myopic macular degeneration (MMD), there is degeneration of the retinal pigment epithelial (RPE) layer, and associated photoreceptors, resulting in vision loss. There is currently no standard treatment for MMD.
Transplantation of intact sheets of RPE and suspensions of isolated individual RPE cells as well as autologous translocation of RPE cells has been attempted as treatment for AMD. Human photoreceptors are comprised of two cell types-rods and cones. Both have a close relationship with the outermost retinal cells, the retinal pigmented epithelium (RPE). The RPE is located between the choroid and the photoreceptors. The RPE maintains photoreceptor function by recycling photopigments,delivering, metabolizing and storing vitamin A, phagocytosing rod photoreceptor outer segments, transporting iron and small molecules between retina and choroid, maintaining Bruch's membrane and absorbing stray light to allow better image resolution. In essence, the RPE layer is critical to the function and health of photoreceptors and the retina as a whole.
Human PRE (hRPE) transplantation may be a viable option for treatment of degenerative diseases of the retina.
MA09-hRPE cells are fully differentiated human RPE cells derived from embryonic stem cells. Transplanted hRPE cells prepared by Advanced Cell Technology have been studied in rodent models of macular degenerative disease. The data suggests that the subretinal injection of ACT's hRPE cell products rescues, or at least delays, loss of visual function in two animal models of retinal degenerative diseases.
The main purpose of this study is to evaluate the safety and tolerability of MA09-hRPE cellular therapy in patients with Myopic Macular Degeneration (MMD). Another objective is to evaluate potential efficacy endpoints to be used in future studies of RPE cellular therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MA09-hRPE Cellular Therapy | Experimental | Biological: MA09-hRPE Cellular TherapyMA09-hRPE cells for transplantation will be provided by Ocata Therapeutics as a suspension frozen to the temperature of liquid nitrogen (approximately -196 °C). They will be processed at UCLA under GMPs according to protocol. Following vitrectomy performed under general anesthesia or waking sedation at the surgeon's discretion, hRPE cells will be introduced into a subretinal bleb formed by the injection of balanced salt solution (BSS). Direct viewing will guide the implantation of thawed and washed MA09-hRPE cells, resuspended in BSS, into the created bleb over a period of one minute. To avoid cell reflux, the cannula used to introduce the cells will be held in position for an additional minute. A suspension of either 50,000 MA09-hRPE cells (first cohort), 100,000 MA09-hRPE cells (second cohort), 150,000 MA09-hRPE cells (third cohort) or 200,000 MA09-hRPE cells (fourth cohort) in 150 uL of BSS plus will be implanted over 1 minute in the space created. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (33 listed)
- Adult male or female over 40 years of age.
- Patient should be in sufficiently good health to reasonably expect survival for at least four years after treatment
- Axial myopia of equal to or greater than -8 diopters and/or axial length equal to or greater than 28 mm
- Clinical findings consistent with MMD with evidence of one or more areas of >250microns of geographic atrophy (as defined in the Age-Related eye Disease Study [AREDS] study) involving the central fovea.
- GA defined as attenuation or loss of RPE as observed by biomicroscopy, OCT, and FA.
Key exclusion criteria (28 listed)
- Presence of active or inactive CNV.
- Presence of a posterior staphyloma.
- Presence or history of retinal dystrophy, retinitis pigmentosa, chorioretinitis, central serious choroidopathy, diabetic retinopathy or other retinal vascular or degenerative disease (i.e. AMD) other than MMD.
- History of optic neuropathy.
- Macular atrophy due to causes other than MMD.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MA09-hRPE Cellular TherapyA suspension of either 50,000 MA09-hRPE cells (first cohort), 100,000 MA09-hRPE cells (second cohort), 150,000 MA09-hRPE cells (third cohort) or 200,000 MA09-hRPE cells (fourth cohort) in 150 uL of BSS plus will be implanted over 1 minute in the space created. | Biological | MA09-hRPE Cellular Therapy |
Primary outcome
Safety of hESC-derived RPE cells
Time frame: 12 months
The transplantation of hESC-derived RPE cells MA09-hRPE will be considered safe and tolerated in the absence of: * Any grade 2 (NCI grading system) or greater adverse event related to the cell product * Any evidence that the cells are contaminated with an infectious agent * Any evidence that the cells show tumorigenic potential
2 secondary outcomes
Evidence of successful engraftment
Time frame: 12 months
Evidence of rejection
Time frame: 12 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2016.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven Schwartz, MD principal investigator
University of California, Los Angeles
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing MA09-hRPE Cellular Therapy in people with Myopic Macular Degeneration, run by University of California, Los Angeles.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 33 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 18 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of hESC-derived RPE cells (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jul 2016; AzTrials last refreshed its copy on 31 Oct 2026.