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This study will evaluate the safety and efficacy of a recombinant adeno-associated virus vector expressing retinoschisin (rAAV2tYF-CB-hRS1) in patients with X-linked retinoschisis. Up to 27 participants will be enrolled and 3 dose levels will be evaluated in a dose escalation format.
This will be a non-randomized, open label, Phase 1/2 dose escalation study.
Up to 27 participants will be enrolled. Each participant will receive the study agent by intravitreal injection in one eye on a single occasion. Enrollment will begin with the lowest dose and will proceed to higher doses only after review of safety data by a Data and Safety Monitoring Committee (DSMC). Participants in the dose escalation phase will be ≥ 18 years of age. After the maximum tolerated dose is identified individuals ≥ 6 years of age will be enrolled.
Safety will be measured by the number and proportion of participants experiencing adverse events and immune response to RS1. Efficacy will be measured by evaluation of changes in visual function and schisis cavity size.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Groups 1A and 1B | Experimental | Subjects at least 18 y/o treated with a lower dose of rAAV2tYF-CB-hRS1 study drug. |
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| Groups 2 and 2A | Experimental | Subjects at least 6 y/o treated with a middle dose of rAAV2tYF-CB-hRS1 study drug. |
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| Group 3 | Experimental | Subjects at least 18 y/o treated with a higher dose of rAAV2tYF-CB-hRS1 study drug. |
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| Group 4 | Experimental | Subjects at least 6 y/o treated with a maximum tolerated dose of rAAV2tYF-CB-hRS1 study drug determined for Groups 1A, 1B, 2 and 3. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| rAAV2tYF-CB-hRS1 | Biological | adeno-associated virus vector expressing retinoschisin |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Experiencing Adverse Events | Number of participants with ocular adverse events, assessed by standard ophthalmic examination, including slit lamp biomicroscopy, tonometry, and indirect ophthalmoscopy. | From Day 0 to Month 12 (12 months) |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Best Corrected Visual Acuity (BCVA) | Change in ETDRS (Early Treatment of Diabetic Retinopathy) Letter Score. Minimum value=0; Maximum value=100. Higher scores indicate better visual acuity. Change = 12 Mo value - Baseline value | From Day 0 to Month 12 (12 Months) |
| Change From Baseline in Schisis Cavity Size on Optical Coherence Tomography (OCT) |
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Inclusion Criteria include:
Exclusion Criteria include:
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| Name | Affiliation | Role |
|---|---|---|
| Theresa Heah, MD | Applied Genetics Technologies Corporation | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California San Francisco, Dept. of Ophthalmology | San Francisco | California | 94143 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22245536 | Background | Molday RS, Kellner U, Weber BH. X-linked juvenile retinoschisis: clinical diagnosis, genetic analysis, and molecular mechanisms. Prog Retin Eye Res. 2012 May;31(3):195-212. doi: 10.1016/j.preteyeres.2011.12.002. Epub 2012 Jan 3. |
| Label | URL |
|---|---|
| AGTC website | View source |
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No participants have completed the study at this time because the study is ongoing (overall status: active, not recruiting). All enrolled participants are in long term follow-up.
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| ID | Title | Description |
|---|---|---|
| FG000 | rAAV2tYF-CB-hRS1 1 x 10^11 vg Per Eye | Group 1A/1B: Adult participants were administered a single intravitreal (IVT) injection of rAAV2tYF-CB-hRS1, once in the study eye, at a dose of 1 x 10^11 vg/eye and followed for a minimum of 12 months after dose administration. |
| FG001 | rAAV2tYF-CB-hRS1 3 x 10^11 vg Per Eye | Group 2/2A: Adult and pediatric participants were administered a single intravitreal (IVT) injection of rAAV2tYF-CB-hRS1, once in the study eye, at a dose of 3 x 10^11 vg/eye and followed for a minimum of 12 months after dose administration. |
| FG002 | rAAV2tYF-CB-hRS1 6 x 10^11 vg Per Eye | Group 3/4: Adult participants were administered a single intravitreal (IVT) injection of rAAV2tYF-CB-hRS1, once in the study eye, at a dose of 6 x 10^11 vg/eye and followed for a minimum of 12 months after dose administration. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | rAAV2tYF-CB-hRS1 1 x 10^11 vg Per Eye | Group 1A/1B: Adult participants were administered a single intravitreal (IVT) injection of rAAV2tYF-CB-hRS1, once in the study eye, at a dose of 1 x 10^11 vg/eye and followed for a minimum of 12 months after dose administration. |
| BG001 | rAAV2tYF-CB-hRS1 3 x 10^11 vg Per Eye |
| 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 | Number of Participants Experiencing Adverse Events | Number of participants with ocular adverse events, assessed by standard ophthalmic examination, including slit lamp biomicroscopy, tonometry, and indirect ophthalmoscopy. | All treated study participants with ocular treatment-emergent adverse events (TEAEs). | Posted | Count of Participants | Participants | From Day 0 to Month 12 (12 months) |
|
Study Day 0 through Month 12- Adverse Events; Study ongoing: adverse events beyond Month 12 to be updated at a later date
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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 | rAAV2tYF-CB-hRS1 1 x 10^11 vg Per Eye | Group 1A/1B: Adult participants were administered a single intravitreal (IVT) injection of rAAV2tYF-CB-hRS1, once in the study eye, at a dose of 1 x 10^11 vg/eye and followed for a minimum of 12 months after dose administration. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Retinal detachment | Eye disorders | MedDRA (20.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Keratic precipitates | Eye disorders | MedDRA (20.0) | Systematic Assessment | Ocular |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Matt Feinsod | AGTC | 386-462-2204 | 7202 | mfeinsod@agtc.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 21, 2019 | May 15, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 8, 2017 | May 15, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D041441 | Retinoschisis |
| D012162 | Retinal Degeneration |
| ID | Term |
|---|---|
| D012164 | Retinal Diseases |
| D005128 | Eye Diseases |
| D015785 | Eye Diseases, Hereditary |
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Change in cystic cavity volume (mm^3), obtained from spectral domain optical coherence tomography (SD-OCT) of the retina, yielding volumetric measures of schisis cavity size and total cyst cavity. Change = 12 Mo value - Baseline value |
| From Day 0 to Month 12 (12 months) |
| Change From Baseline in B-wave Amplitude in Electroretinogram (ERG) Responses | Change in dark-adapted 3.0 B-wave amplitude (μV). Change = 12 Mo value - Baseline value | From Day 0 to Month 12 (12 months) |
| University of Miami - Miller School of Medicine Bascom Palmer Eye Institute |
| Miami |
| Florida |
| 33136 |
| United States |
| The Wilmer Eye Institute, Johns Hopkins Hospital | Baltimore | Maryland | 21287 | United States |
| Massachusetts Eye and Ear Infirmary | Boston | Massachusetts | 02114 | United States |
| University of Michigan Kellogg Eye Center | Ann Arbor | Michigan | 48105 | United States |
| Duke Eye Center, Duke University Medical Center | Durham | North Carolina | 27710 | United States |
| Casey Eye Institute, Oregon Health and Sciences University | Portland | Oregon | 97239 | United States |
| Retina Foundation of the Southwest | Dallas | Texas | 75231 | United States |
| Baylor College of Medicine, Alkek Eye Center | Houston | Texas | 77030 | United States |
Group 2/2A: Adult and pediatric participants were administered a single intravitreal (IVT) injection of rAAV2tYF-CB-hRS1, once in the study eye, at a dose of 3 x 10^11 vg/eye and followed for a minimum of 12 months after dose administration. |
| BG002 | rAAV2tYF-CB-hRS1 6 x 10^11 vg Per Eye | Group 3/4: Adult participants were administered a single intravitreal (IVT) injection of rAAV2tYF-CB-hRS1, once in the study eye, at a dose of 6 x 10^11 vg/eye and followed for a minimum of 12 months after dose administration. |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
|
Group 2/2A: Adult and pediatric participants were administered a single intravitreal (IVT) injection of rAAV2tYF-CB-hRS1, once in the study eye, at a dose of 3 x 10^11 vg/eye and followed for a minimum of 12 months after dose administration. |
| OG002 | rAAV2tYF-CB-hRS1 6 x 10^11 vg Per Eye | Group 3/4: Adult participants were administered a single intravitreal (IVT) injection of rAAV2tYF-CB-hRS1, once in the study eye, at a dose of 6 x 10^11 vg/eye and followed for a minimum of 12 months after dose administration. |
|
|
| Secondary | Change From Baseline in Best Corrected Visual Acuity (BCVA) | Change in ETDRS (Early Treatment of Diabetic Retinopathy) Letter Score. Minimum value=0; Maximum value=100. Higher scores indicate better visual acuity. Change = 12 Mo value - Baseline value | All treated study participants with available data. | Posted | Mean | Standard Deviation | ETDRS Letter Score | From Day 0 to Month 12 (12 Months) |
|
|
|
| Secondary | Change From Baseline in Schisis Cavity Size on Optical Coherence Tomography (OCT) | Change in cystic cavity volume (mm^3), obtained from spectral domain optical coherence tomography (SD-OCT) of the retina, yielding volumetric measures of schisis cavity size and total cyst cavity. Change = 12 Mo value - Baseline value | All treated study participants with available data. | Posted | Mean | Standard Deviation | Cystic Cavity Volume (mm^3) | From Day 0 to Month 12 (12 months) |
|
|
|
| Secondary | Change From Baseline in B-wave Amplitude in Electroretinogram (ERG) Responses | Change in dark-adapted 3.0 B-wave amplitude (μV). Change = 12 Mo value - Baseline value | All treated study participants with available data. | Posted | Mean | Standard Deviation | μV | From Day 0 to Month 12 (12 months) |
|
|
|
| 0 |
| 6 |
| 2 |
| 6 |
| 6 |
| 6 |
| EG001 | rAAV2tYF-CB-hRS1 3 x 10^11 vg Per Eye | Group 2/2A: Adult and pediatric participants were administered a single intravitreal (IVT) injection of rAAV2tYF-CB-hRS1, once in the study eye, at a dose of 3 x 10^11 vg/eye and followed for a minimum of 12 months after dose administration. | 0 | 8 | 1 | 8 | 7 | 8 |
| EG002 | rAAV2tYF-CB-hRS1 6 x 10^11 vg Per Eye | Group 3/4: Adult participants were administered a single intravitreal (IVT) injection of rAAV2tYF-CB-hRS1, once in the study eye, at a dose of 6 x 10^11 vg/eye and followed for a minimum of 12 months after dose administration. | 0 | 13 | 1 | 13 | 13 | 13 |
| Atrial Fibrillation | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
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| Faecaloma | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
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| Cerebellar stroke | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
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| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
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| Vitritis | Eye disorders | MedDRA (20.0) | Systematic Assessment | Ocular |
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| Anterior chamber cells | Eye disorders | MedDRA (20.0) | Systematic Assessment | Ocular |
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| Vitreous floaters | Eye disorders | MedDRA (20.0) | Systematic Assessment | Ocular |
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| Eye pain | Eye disorders | MedDRA (20.0) | Systematic Assessment | Ocular |
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| Vitreal cells | Eye disorders | MedDRA (20.0) | Systematic Assessment | Ocular |
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| Conjunctival haemorrhage | Eye disorders | MedDRA (20.0) | Systematic Assessment | Ocular |
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| Cataract subcapsular | Eye disorders | MedDRA (20.0) | Systematic Assessment | Ocular |
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| Vision blurred | Eye disorders | MedDRA (20.0) | Systematic Assessment | Ocular |
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| Vitreous haze | Eye disorders | MedDRA (20.0) | Systematic Assessment | Ocular |
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| Visual impairment | Eye disorders | MedDRA (20.0) | Systematic Assessment | Ocular |
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| Anterior chamber inflammation | Eye disorders | MedDRA (20.0) | Systematic Assessment | Ocular |
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| Retinal tear | Eye disorders | MedDRA (20.0) | Systematic Assessment | Ocular |
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| Anterior chamber flare | Eye disorders | MedDRA (20.0) | Systematic Assessment | Ocular |
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| Cataract | Eye disorders | MedDRA (20.0) | Systematic Assessment | Ocular |
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| Conjunctival hyperaemia | Eye disorders | MedDRA (20.0) | Systematic Assessment | Ocular |
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| Eye pruritus | Eye disorders | MedDRA (20.0) | Systematic Assessment | Ocular |
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| Photophobia | Eye disorders | MedDRA (20.0) | Systematic Assessment | Ocular |
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| Photopsia | Eye disorders | MedDRA (20.0) | Systematic Assessment | Ocular |
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| Lenticular opacities | Eye disorders | MedDRA (20.0) | Systematic Assessment | Ocular |
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| Conjunctival oedema | Eye disorders | MedDRA (20.0) | Systematic Assessment | Ocular |
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| Eyelid ptosis | Eye disorders | MedDRA (20.0) | Systematic Assessment | Ocular |
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| Iridocyclitis | Eye disorders | MedDRA (20.0) | Systematic Assessment | Ocular |
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| Lacrimation increased | Eye disorders | MedDRA (20.0) | Systematic Assessment | Ocular |
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| Ocular discomfort | Eye disorders | MedDRA (20.0) | Systematic Assessment | Ocular |
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| Retinal detachment | Eye disorders | MedDRA (20.0) | Systematic Assessment | Ocular |
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| Retinal haemorrhage | Eye disorders | MedDRA (20.0) | Systematic Assessment | Ocular |
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| Injection site haemorrhage | General disorders | MedDRA (20.0) | Systematic Assessment | Ocular |
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| Injection site discomfort | General disorders | MedDRA (20.0) | Systematic Assessment | Ocular |
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| Intraocular pressure | Investigations | MedDRA (20.0) | Systematic Assessment | Ocular |
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| Optic neuritis | Nervous system disorders | MedDRA (20.0) | Systematic Assessment | Ocular |
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| Pyrexia | General disorders | MedDRA (20.0) | Systematic Assessment | Non-ocular |
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| Feeling hot | General disorders | MedDRA (20.0) | Systematic Assessment | Non-ocular |
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| Blood pressure increased | Investigations | MedDRA (20.0) | Systematic Assessment | Non-ocular |
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| Weight increased | Investigations | MedDRA (20.0) | Systematic Assessment | Non-ocular |
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| White blood cell count increased | Investigations | MedDRA (20.0) | Systematic Assessment | Non-ocular |
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| Headache | Nervous system disorders | MedDRA (20.0) | Systematic Assessment | Non-ocular |
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| Viral upper respiratory tract infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment | Non-ocular |
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| Abdominal discomfort | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment | Non-ocular |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment | Non-ocular |
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| Dyspepsia | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment | Non-ocular |
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| Nausea | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment | Non-ocular |
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| Stomatitis | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment | Non-ocular |
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| Leukocytosis | Blood and lymphatic system disorders | MedDRA (20.0) | Systematic Assessment | Non-ocular |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA (20.0) | Systematic Assessment | Non-ocular |
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| Increased appetite | Metabolism and nutrition disorders | MedDRA (20.0) | Systematic Assessment | Non-ocular |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment | Non-ocular |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment | Non-ocular |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment | Non-ocular |
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| Insomnia | Psychiatric disorders | MedDRA (20.0) | Systematic Assessment | Non-ocular |
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