Clinical trial NCT03316560: Safety and Efficacy of rAAV2tYF-GRK1-RPGR in Subjects With X-linked Retinitis Pigmentosa Caused by RPGR Mutations
Official title: A Phase 1/2 Open-Label Dose Escalation Study to Evaluate the Safety and Efficacy of AGTC-501 (rAAV2tYF-GRK1-RPGR) and a Phase 2 Randomized, Controlled, Masked, Multi-center Study Comparing Two Doses of AGTC-501 in Male Subjects With X-linked Retinitis Pigmentosa Confirmed by a Pathogenic Variant in the RPGR Gene
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: X-Linked Retinitis Pigmentosa
Keywords: XLRP
retinal degeneration
RPGR
adeno-associated virus
gene therapy
AAV
Lead sponsor: Beacon Therapeutics
Sponsor class: INDUSTRY
First posted: 2017-10-20
Enrollment: 29
Sex: MALE
Minimum age (years): 6
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Number and proportion of Adverse Events
timeFrame: Day 0 - Month 36
measure: Number and proportion of participants experiencing abnormal clinically relevant hematology or clinical chemistry parameters.
timeFrame: Day 0 - Month 36
Secondary outcomes:
measure: Changes from baseline in visual function as measured by mesopic microperimetry in the treated eye compared to the untreated eye
timeFrame: Day 0 - Month 36
measure: Changes from baseline in visual acuity
timeFrame: Day 0 - Month 36
measure: Changes from baseline in retinal structure as assessed by spectral-domain optical coherence tomography (SD-OCT)
timeFrame: Day 0 - Month 36
measure: Changes from baseline in quality of life questionnaire responses
timeFrame: Day 0 - Month 36
measure: Change from baseline in visual function by light-adapted perimetry
timeFrame: Day 0 - Month 36
measure: Change from baseline in fundus imaging
timeFrame: Day 0 - Month 36
measure: Change from baseline in full-field light sensitivity threshold (FST)
timeFrame: Day 0 - Month 36
measure: Changes from baseline in visual function by dark-adapted full field perimetry (for subjects treated peripherally)
timeFrame: Day 0 - Month 36
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Eye Institute
state: Ohio
city: Portland
country: United States
facility: Casey Eye Institute
state: Oregon
city: Dallas
country: United States
facility: Retina Foundation of the Southwest
state: Texas
Study officials:
References: