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Phase II gene therapy study, involving a total of 6 male patients with choroideremia. The study will be conducted at the Bascom Palmer Eye Institute, University of Miami. Patients will be required to attend a total of 11 study visits over a 24 month period with an additional 3 year follow-up.
This is a Phase II, open label study involving patients with a clinical phenotype of choroideremia and a confirmed CHM genotype. Following consent, patients will be required to attend an initial screening visit (Visit 1). Within 2 weeks of the screening visit patients will undergo a surgical procedure (Visit 2) under general anesthesia which will include a standard vitrectomy, retinal detachment and administration of a subretinal injection of AAV2-REP1 (1x1011 genome particles). Patients will be required to attend a further 9 study visits (Visits 3-11) over a 24 month period for functional, and anatomical assessments as well as monitoring of adverse events. The primary endpoint is the change from baseline in visual acuity in the study eye, compared to control eye. Secondary study endpoints are, change from baseline in autofluorescence evaluation, microperimetry readings and other anatomic and functional outcomes (all in the study eye compared to control eye). Secondary endpoints also include safety assessments to be conducted throughout the study. The fellow eyes of these patients will be utilized as controls in this study and will receive no study treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Injection of AAV2-REP1 | Experimental | Injection of AAV-REP1, 1.00x10e11 vg, subretinal injection of total volume of 100 μL. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Injection of AAV2-REP1 (10e11 vg) | Biological | Single Group: single arm study |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Best Corrected Visual Acuity From Baseline | Patients will have an assessment of visual acuity using the Early Treatment of Diabetic Retinopathy Study (ETDRS) vision charts in both eyes. Low Luminance BCVA was measured by placing a 2.0 log unit neutral density filter over the best correction for that eye and having the participant read the normally illuminated ETDRS chart and was reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). The study eye was defined as the eye that met inclusion/exclusion criteria with the worst standard BCVA. If the BCVA in both eyes was similar the Patient determines the worse eye be selected as the study eye. A positive change from baseline indicates an improvement and a negative change from baseline indicates a worsening. | Baseline, 24 Months |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Retinal Macular Autofluorescence From Baseline | Measured in mm^2 by Fundus Autofluorescence and shows changes in the integrity and metabolism of retinal cells. A negative change from baseline indicates a decrease in size of the retained retina (worsening; disease progression). | 12 and 24 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| BYRON LAM, MD | UNIVERSITY OF MIAMI, BASCOM PALMER EYE INSTITUTE | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Bascom Palmer Eye Institute, University of Miami | Miami | Florida | 33136 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30194931 | Derived | Davis JL. The Blunt End: Surgical Challenges of Gene Therapy for Inherited Retinal Diseases. Am J Ophthalmol. 2018 Dec;196:xxv-xxix. doi: 10.1016/j.ajo.2018.08.038. Epub 2018 Sep 5. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Injection of AAV2-REP1 | Injection of AAV-REP1, 1.00x10e11 vg, subretinal injection of total volume of 100 μL. Injection of AAV2-REP1 (10e11 vg): Single Group: single arm study |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Injection of AAV2-REP1 | Injection of AAV-REP1, 1.00x10e11 vg, subretinal injection of total volume of 100 μL. Injection of AAV2-REP1 (10e11 vg): Single Group: single arm study |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Best Corrected Visual Acuity From Baseline | Patients will have an assessment of visual acuity using the Early Treatment of Diabetic Retinopathy Study (ETDRS) vision charts in both eyes. Low Luminance BCVA was measured by placing a 2.0 log unit neutral density filter over the best correction for that eye and having the participant read the normally illuminated ETDRS chart and was reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). The study eye was defined as the eye that met inclusion/exclusion criteria with the worst standard BCVA. If the BCVA in both eyes was similar the Patient determines the worse eye be selected as the study eye. A positive change from baseline indicates an improvement and a negative change from baseline indicates a worsening. | Posted | Mean | Standard Deviation | Letters | Baseline, 24 Months |
|
24 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Injection of AAV2-REP1 | Injection of AAV-REP1, 1.00x10e11 vg, subretinal injection of total volume of 100 μL. Injection of AAV2-REP1 (10e11 vg): Single Group: single arm study |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cataract | Eye disorders | MedDRA 21.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Byron Lam , MD | University of Miami | 305-326-6021 | blam@med.miami.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 18, 2015 | Jun 25, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D015794 | Choroideremia |
| ID | Term |
|---|---|
| D015785 | Eye Diseases, Hereditary |
| D005128 | Eye Diseases |
| D015862 | Choroid Diseases |
| D014603 | Uveal Diseases |
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| Changes in Microperimetry From Baseline |
Microperimetry assessments. A negative change from baseline indicates disease worsening. |
| Baseline to 24 months |
| Number of Participants Who Experience an Adverse Event | Adverse events during treatment and follow-up period | 24 months |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
Injection of AAV-REP1, 1.00x10e11 vg, subretinal injection of total volume of 100 μL. Injection of AAV2-REP1 (10e11 vg): Single Group: single arm study |
|
|
| Secondary | Change in Retinal Macular Autofluorescence From Baseline | Measured in mm^2 by Fundus Autofluorescence and shows changes in the integrity and metabolism of retinal cells. A negative change from baseline indicates a decrease in size of the retained retina (worsening; disease progression). | Posted | Mean | Standard Deviation | mm^2 | 12 and 24 months |
|
|
|
| Secondary | Changes in Microperimetry From Baseline | Microperimetry assessments. A negative change from baseline indicates disease worsening. | Posted | Mean | Standard Deviation | Average Threshold dB | Baseline to 24 months |
|
|
|
| Secondary | Number of Participants Who Experience an Adverse Event | Adverse events during treatment and follow-up period | Posted | Count of Participants | Participants | 24 months |
|
|
|
| 0 |
| 6 |
| 0 |
| 6 |
| 6 |
| 6 |
| Diplopia | Eye disorders | MedDRA 21.1 | Systematic Assessment |
|
| Vitreous Cells | Eye disorders | MedDRA 21.1 | Systematic Assessment |
|
| Anterior Chamber Cells | Eye disorders | MedDRA 21.1 | Systematic Assessment |
|
| Extrafoveal macular retinal hole in area of nonfunctioning retina | Eye disorders | MedDRA 21.1 | Systematic Assessment |
|
| Subretinal fluid | Eye disorders | MedDRA 21.1 | Systematic Assessment |
|
| Conjunctiva hemorrhage, edema | Eye disorders | MedDRA 21.1 | Systematic Assessment |
|
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| D030342 |
| Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D040181 | Genetic Diseases, X-Linked |