X-Linked Retinitis Pigmentosa
Conditions
Keywords
XLRP, retinal degeneration, RPGR, adeno-associated virus, gene therapy, AAV
Brief summary
This study will evaluate the safety and efficacy of a recombinant adeno-associated virus vector (rAAV2tYF-GRK1-RPGR) in patients with X-linked retinitis pigmentosa caused by RPGR mutations.
Detailed description
This protocol includes a non-randomized, open-label, Phase 1/2 study (HORIZON). Approximately 30 participants will be enrolled into the dose escalation study (HORIZON). Each participant will receive the study agent by subretinal 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). There are a total of 15 visits over approximately 36 months, and long-term follow-up evaluations annually at years 4 and 5.
Interventions
BIOLOGICALrAAV2tYF-GRK1-RPGR
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
6 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
Phase 1/2 Dose Escalation Inclusion Criteria: * Male subjects with a documented RPGR mutation * Clinical diagnosis of X-linked retinitis pigmentosa (XLRP) * Best-corrected visual acuity not better than 78 ETDRS letters (20/32) in the study eye; * Ability to perform tests of visual and retinal function and structure and ability to comply with other research procedures; * Detectable baseline mean macular sensitivity, as measured by microperimetry. * Have detectable Ellipsoid Zone (EZ) line during the pre-treatment period as assessed by OCT and confirmed by the CRC. Phase 1/2 Dose Escalation
Exclusion criteria
* Pre-existing eye conditions that would preclude the planned surgery or interfere with the interpretation of study endpoints or increase the risk of surgical complications (for example, glaucoma, corneal or lenticular opacities, diabetic retinopathy, retinal vasculitis); * Use of anti-coagulant agents that may alter coagulation within 7 days prior to study agent administration; * Use of systemic corticosteroids or other immunosuppressive medications within 3 months prior to enrollment; * Any other condition that would prevent a subject from completing follow-up examinations during the course of the study; * Any other condition or reason that, in the opinion of the investigator, makes the subject unsuitable for the study; * Previous receipt of any AAV gene therapy product; * Monocular or having BCVA less than 20/800 in the fellow eye
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number and proportion of Adverse Events | Day 0 - Month 36 | Number and proportion of participants experiencing Grade 3 or higher local (ocular) or systemic treatment-emergent adverse events that occur during the 36 months after study agent administration; number and proportion of participants experiencing treatment-emergent AEs, including treatment-emergent serious AEs; |
| Number and proportion of participants experiencing abnormal clinically relevant hematology or clinical chemistry parameters. | Day 0 - Month 36 | — |
Secondary
| Measure | Time frame |
|---|---|
| Changes from baseline in retinal structure as assessed by spectral-domain optical coherence tomography (SD-OCT) | Day 0 - Month 36 |
| Changes from baseline in quality of life questionnaire responses | Day 0 - Month 36 |
| Change from baseline in visual function by light-adapted perimetry | Day 0 - Month 36 |
| Changes from baseline in visual function as measured by mesopic microperimetry in the treated eye compared to the untreated eye | Day 0 - Month 36 |
| Change from baseline in full-field light sensitivity threshold (FST) | Day 0 - Month 36 |
| Changes from baseline in visual function by dark-adapted full field perimetry (for subjects treated peripherally) | Day 0 - Month 36 |
| Change from baseline in fundus imaging | Day 0 - Month 36 |
| Changes from baseline in visual acuity | Day 0 - Month 36 |
Countries
United States
Outcome results
None listed