X-Linked Retinitis Pigmentosa
Conditions
Keywords
XLRP, retinal degeneration, RPGR, adeno-associated virus, gene therapy, AAV
Brief summary
This Phase 2 study is a non-randomized, open-label, study of the safety of AGTC-501 in participants with XLRP who have previously been treated with a full-length AAV vector-based gene therapy targeting RPGR protein.
Detailed description
This is a Phase 2, open-label, multicenter study to evaluate the safety of 2 doses of AGTC-501 administered as a single subretinal injection in participants with XLRP who have previously been treated with a full-length AAV vector-based gene therapy targeting RPGR protein. The trial includes a screening period of up to 60 days and a 5 year study period. Each participant will receive a single subretinal injection of one of two dose levels of AGTC-501 in their previously untreated eye. There will be 3 groups. Group 1 will receive the high dose and include up to 12 participants, Group 2 will receive the low dose and will include 6 participants, and Group 3 will include \ 3-6 participants. Participants in Groups 1 and 2 will receive the standard corticosteroid regimen. A single subretinal injection of the high dose AGTC-501 will be administered to participants in Group 1 (n = 12), while participants in Group 2 (n = 6) will receive a single subretinal injection of low dose AGTC-501. Group 2 (low dose AGTC-501, Standard Steroid) will be dosed before moving to Group 3. After 6 Group 1 (high dose) study participants reach post-operative Month 1, all data will be reviewed by the DSMC. If no safety signals arise, additional participants, Group 3 (n \ 3-6), will receive a single subretinal injection of the high dose with a modified course of corticosteroids.
Interventions
BIOLOGICALAGTC-501 (high dose and standard corticosteroid regimen)
Adeno-associated virus vector expressing a human RPGR gene
BIOLOGICALAGTC-501 (low dose and standard corticosteroid regimen)
Adeno-associated virus vector expressing a human RPGR gene
BIOLOGICALAGTC-501 (high dose and modified corticosteroid regimen)
Adeno-associated virus vector expressing a human RPGR gene
Sponsors
Beacon Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Be ≥12 years of age * Have one eye previously treated with an AAV vector-based gene therapy designed to provide full-length functioning RPGR protein. * Have a BCVA no better than 78 letters and no worse than 34 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 detectable baseline mean macular sensitivity measured by MAIA microperimetry, as determined by the Investigator and confirmed by the Central Reading Center (CRC). * Have detectable EZ line in the study eye as assessed by SD-OCT and confirmed by the CRC.
Exclusion criteria
* Have other known disease-causing mutations documented in the participant's medical history or identified through a retinal dystrophy gene panel that, in the opinion of the Investigator, would interfere with the potential therapeutic effect of the study agent or the quality of the assessments. * Have pre-existing eye conditions that would preclude the planned surgery, interfere with the interpretation of study endpoints, or increase the risk of surgical complications * Had intraocular surgery within 90 days of study treatment administration. * Have any active ocular/intraocular infection or inflammation * Have a history of steroid-induced raised IOP of \>25 mmHg following corticosteroid exposure, despite topical IOP-lowering pharmacologic therapy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary safety outcome is the number of participants experiencing Grade 3 or higher local (ocular) or non-ocular treatment-emergent adverse events, including treatment-emergent serious adverse events (SAEs). | Day 0 - Month 12 |
| The primary safety outcome is the proportion of participants experiencing Grade 3 or higher local (ocular) or non-ocular treatment-emergent adverse events, including treatment-emergent serious adverse events (SAEs). | Day 0 - Month 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in mean sensitivity across the whole grid, as measured by MAIA (Macular Integrity Assessment) microperimetry, assess photoreceptor function under low light | Day 0 - Month 12 | — |
| Response, as measured by MAIA (Macular Integrity Assessment) microperimetry, where response is defined as a greater than or equal to 7 decibel (dB) visual sensitivity improvement from baseline in at least 5 loci. | Day 0 - Month 12 | — |
| Change from baseline in full-field stimulus threshold (FST) | Day 0 - Month 12 | As assessed by full-field stimulus threshold (FST); FST measures the sensitivity of the visual field by testing for the lowest luminance flash which elicits a visual sensation perceived |
| Change from baseline in Best Corrected Visual Acuity (BCVA) using Early-Treatment Diabetic Retinopathy Study (ETDRS) visual acuity | Day 0 - Month 12 | — |
| Change from baseline in Low Luminance Visual Acuity (LLVA) using Early-Treatment Diabetic Retinopathy Study (ETDRS) visual acuity | Day 0 - Month 12 | — |
| The number of participants experiencing treatment-emergent AEs of ocular/non-ocular adverse events, including treatment-emergent serious AEs. | Day 0 - Month 12 | — |
| Change from baseline in ellipsoid zone (EZ) area measured by spectral domain optical coherence tomography (SD OCT) | Day 0 - Month 12 | — |
| Change from baseline in seven domain scores from a Michigan Retinal Degeneration Questionnaire (MRDQ) | Day 0 - Month 12 | — |
| Change from baseline in Ora-VNC (visual navigation course) mobility test score | Day 0 - Month 12 | As assessed by functional assessment Ora-VNC (visual navigation course) mobility course |
| Change from baseline in the MObility Standardized Test-Virtual Reality (MOST-VR) mobility course test score | Day 0 - Month 12 | As measured by the MObility Standardized Test-Virtual Reality (MOST-VR) mobility course |
| Proportion of responding eyes in treated versus control eyes at Month 12 where responder is defined as an improvement of at least 15-letters on low-luminance visual acuity (LLVA) | Day 0 - Month 12 | — |
| The proportion of participants experiencing treatment-emergent AEs of ocular/non-ocular adverse events, including treatment-emergent serious AEs. | Day 0 - Month 12 | — |
Countries
United States
Outcome results
None listed