X-Linked Retinitis Pigmentosa (XLRP)
Conditions
Keywords
XLRP, retinal degeneration, RPGR, adeno-associated virus, AAV, gene therapy
Brief summary
The purpose of this Phase 2 Study is to see if the investigational study drug, laruparetigene zovaparvovec, also known as AGTC-501, given in both eyes, is safe and works to preserve and/or improve vision and other symptoms of XLRP.
Detailed description
XLRP is a genetic (inherited) eye disease that affects cells in the retina (the lining of the back of the eye that detects light). It causes night blindness and gradual worsening of your vision. The purpose of this Phase 2 Study is to see if the investigational study drug, laruparetigene zovaparvovec, also known as AGTC-501, given in both eyes, is safe and works to preserve and/or improve vision and other symptoms of XLRP.
Interventions
BIOLOGICALAdeno-associated virus vector expressing a human RPGR gene
Male participants 12-50 years of age treated by subretinal injection with the dose of AGTC-501
Sponsors
Beacon Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
To evaluate the long-term safety and tolerability of laruparetigene zovaparvovec administered bilaterally via subretinal injection
Eligibility
Sex/Gender
MALE
Age
12 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
General inclusion criteria * Provide written informed consent or assent (per local regulation) prior to the conduct of any study-related procedures. Participants who provide assent must have a parent, guardian, or legal representative provide written informed consent. * Be between 12 and 50 years of age (inclusive) at the time of providing informed consent and assent (as applicable) * Be male (XY chromosome) and have at least 1 documented pathogenic or likely pathogenic variant in the RPGR gene, within exons 1-14 and/or ORF15, from an appropriately certified or accredited laboratory * Have a clinical diagnosis of XLRP * Be in good general health to withstand subretinal surgery and perioperative medications based on a complete physical examination and results from hematology, chemistry, and coagulation analyses performed at screening * Be able and willing, as assessed by the Investigator, to follow study instructions, complete study assessments, comply with the protocol, and attend all study visits * If the participant has a parent or caregiver, the parent or caregiver must be able to follow study instructions, comply with the protocol, and attend study visits with the participant, as required Ocular inclusion criteria (both eyes) * Have a BCVA ≤ 78 letters (approximately Snellen, 20/32) and ≥ 34 letters (approximately Snellen, 20/200) in each eye based on an ETDRS chart at each screening visit. The ETDRS letter score is the main visual acuity inclusion criterion for participants. Participants unable to read the ETDRS letters may use a tumbling "E" chart for the BCVA assessments * Have an LLVA ≤ 64 letters (approximately Snellen, 20/50) in both eyes based on an ETDRS chart at each screening visit. Participants unable to read the ETDRS letters may use a tumbling "E" chart for the LLVA assessments * Have an LLD of \>10 letters * Be able to perform all tests of visual and retinal function and structure in both eyes based on the participant's reliability and fixation, per the Investigator's discretion * Have a detectable mean macular sensitivity by MAIA microperimetry at baseline between 1 and 12 dB in both eyes, as determined by the Investigator and confirmed by the central reading center (CRC), with a fixation loss ≤ 20% at each screening visit * Have a detectable sub-foveal EZ line as assessed by SD-OCT in both eyes as confirmed by the CRC
Exclusion criteria
General
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The number and percentage of participants experiencing Grade 3 or higher ocular or non-ocular treatment-emergent adverse events (TEAEs), including treatment-emergent serious adverse events (SAEs), at Month 12 | Day 0 - Month 12 |
Secondary
| Measure | Time frame |
|---|---|
| The number and percentage of participants experiencing ocular or non-ocular TEAEs, including treatment-emergent SAEs during the Study period | Day 0-5 years |
| Change from baseline in low-luminance visual acuity (LLVA) using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity at Month 12 | Day 0 - Month 12 |
| Change from baseline in mean sensitivity across the whole grid, as measured by macular integrity assessment (MAIA) microperimetry at Month 12 | Day 0 - Month 12 |
| Response, as measured by MAIA microperimetry, where response is defined as a ≥ 7 dB visual sensitivity improvement from baseline in at least 5 loci at Month 12 | Day 0 - Month 12 |
| Change from baseline in full-field stimulus threshold (FST) at Month 12 | Day 0 - Month 12 |
| Change from baseline in best-corrected visual acuity (BCVA) using ETDRS visual acuity at Month 12 | Day 0 - Month 12 |
| Change from baseline in low-luminance deficit using ETDRS visual acuity at Month 12 | Day 0 - Month 12 |
| Proportion of responding eyes at Month 12 where responder is defined as an improvement of at least 15 letters on LLVA | Day 0 - Month 12 |
| Change from baseline in ellipsoid zone (EZ) area measured by spectral domain-optical coherence tomography (SD-OCT) at Month 12 | Day 0 - Month 12 |
| Change from baseline in 7 domain scores from a Michigan Retinal Degeneration Questionnaire (MRDQ) at Month 12 | Day 0 - Month 12 |
| Change from baseline in the Mobility Standardized Test-Virtual Reality (MOST-VR) course test score at Month 12 | Day 0- Month 12 |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORNone None
Outcome results
None listed