Clinical trial NCT04850118: A Clinical Trial Evaluating the Safety and Efficacy of a Single Subretinal Injection of AGTC-501 in Participants With XLRP
Official title: A Randomized, Controlled, Masked, Multi-center Study Evaluating the Efficacy, Safety, and Tolerability of Two Doses of AGTC-501 Compared to an Untreated Control Group in Male Participants With X-linked Retinitis Pigmentosa
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: X-Linked Retinitis Pigmentosa
Keywords: XLRP
retinal degeneration
RPGR
adeno-associated virus
AAV
gene therapy
Lead sponsor: Beacon Therapeutics
Sponsor class: INDUSTRY
First posted: 2021-04-20
Enrollment: 75
Sex: MALE
Minimum age (years): 12
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants are randomized in a 1:1:1 ratio to 1 of 3 groups (high dose, low dose, untreated) control. After 12 months, participants in the untreated group will be evaluated to determine eligibility to receive the high dose of AGTC-501.
Primary purpose: TREATMENT

Brief summary: This study will evaluate and compare the safety, efficacy, and tolerability of 2 doses of a recombinant adeno-associated virus vector (AGTC-501/laruparetigene zovaparvovec )) to an untreated control group in male participants with X-linked retinitis pigmentosa caused by RPGR mutations.

Detailed description: This study is a randomized, controlled, masked, multi-center study evaluating and comparing 2 doses of AGTC-501 to an untreated control group. A single subretinal injection of AGTC-501 Dose 1 or Dose 2 will be administered in participants in 2 treatment groups while participants in the untreated control group will be followed and evaluated, after which they will be evaluated to determine eligibility to receive treatment with AGTC-501 Dose 2.

Approximately 75 eligible male participants between 12 and 50 years of age (inclusive) will be randomized in a 1:1:1 ratio to 1 of 3 groups.

Eligibility criteria: General Inclusion Criteria:

1. Provide written informed consent or assent (per local regulation), prior to the conduct of any study-related procedure. Participants who provide assent must have a parent, guardian, or legal representative provide written informed consent.
2. Be between 12 and 50 years of age (inclusive) at the time of informed consent and assent (as applicable).
3. Be male (XY chromosome) and have at least one documented pathogenic or likely pathogenic variant in the RPGR gene.
4. Have a clinical diagnosis of XLRP.
5. Be able and willing, as assessed by the Investigator, to follow study instructions, complete study assessments, comply with the protocol, and attend study visits for the duration of the study.

   Ocular Inclusion Criteria (Study Eye):
6. Have a BCVA ≤ 78 letters (approximately Snellen, 20/32) and ≥ 34 letters (approximately Snellen, 20/200)
7. Have a LLVA ≤64 letters (approximately Snellen 20/50) in the study eye
8. Be able to perform all tests of visual and retinal function and structure in both eyes based on the participant's reliability, and fixation, in the study eye per the Investigator's discretion.
9. Have an LLD of \> 10 letters in the study eye
10. Have detectable baseline mean macular sensitivity measured by MAIA microperimetry, between 1-12 decibels (dB) in the study eye, as determined by the Investigator and confirmed by the CRC with fixation loss ≤20% at each screening visit.
11. Have a detectable sub-foveal EZ line in the study eye as assessed by spectral domain-optical coherence tomography (SD-OCT) and confirmed by the CRC.

General Exclusion Criteria:

1. 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.
2. For participants with herpes simplex virus (HSV):

   1. Have history of oral or genital herpes and unable and/or unwilling to utilize prophylactic antiviral medication.
   2. Have a history of ocular herpes.
   3. Have active oral or genital herpes or are currently receiving treatment for HSV infection.
3. Have known sensitivity or allergy to systemic corticosteroids or other immunosuppressive medications.
4. Have used anti-coagulant agents that may alter coagulation
5. Have used systemic corticosteroids or other immunosuppressive medications within 3 months prior to screening and/or intend to use during screening. Corticosteroids used on an as-needed basis administered by insufflation, inhalation or local administration to the skin
6. If sexually active or planning to become sexually active, are unwilling to use barrier contraception for 3 months following treatment administration.
7. Are currently participating or recently participated in any other research
8. Have previously received any AAV gene therapy product, stem cell therapy, cell-based therapy, or similar biologics.
9. Have significant media opacity impacting evaluation of the retina or vitreous. administration.
10. Had intraocular surgery within 90 days of study treatment administration.
11. Have any active ocular/intraocular infection or inflammation
12. Have a history of corticosteroid-induced raised IOP of \>25 mmHg following corticosteroid exposure, despite topical IOP-lowering pharmacologic therapy.
13. Have any artificial retinal implant or prosthesis.
14. Have absence of clear ocular media and/or inadequate pupil dilation to facilitate good quality SD-OCT images.
15. Have any history of rhegmatogenous retinal detachment.
16. Have myopia (spherical equivalent) exceeding -10 diopters (or axial length of \>30 mm if the Principal Investigator \[PI\] deems it appropriate to measure) or presence of pathologic myopia in the study eye.
17. Have passed the Low Contrast Ora-VNC mobility course at ≤0.35 lux light level in either eye or binocularly at any screening visit.

Primary outcomes:
measure: The proportion of participants with a ≥15 letter increase from baseline in LLVA
timeFrame: Day 0 - Month 12
Secondary outcomes:
measure: Change from baseline in LLVA (First Key Secondary Endpoint)
timeFrame: Day 0 - Month 12
measure: Change from baseline in mean sensitivity across the whole grid, as measured by MAIA (Second Key Secondary Endpoint) microperimetry
timeFrame: Day 0 - Month 12
measure: Change from baseline in full-field stimulus threshold (FST) (Third Key Secondary Endpoint)
timeFrame: Day 0 - Month 12
Other outcomes:
measure: Number and proportion of treatment-emergent ocular/non-ocular adverse events
timeFrame: Day 0 - Year 5
Locations:
city: Scottsdale
country: United States
facility: Retina Macula Institute of Arizona
state: Arizona
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Jacksonville
country: United States
facility: University of Florida Health Jacksonville, Department of Ophthalmology
state: Florida
city: Miami
country: United States
facility: Bascom Palmer Eye Institute- University of Miami
state: Florida
city: Carmel
country: United States
facility: Midwest Eye Institute (Retina Partners Midwest)
state: Indiana
city: Baltimore
country: United States
facility: Wilmer Eye Institute at Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Ophthalmic Consultants of Boston
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Durham
country: United States
facility: Duke Eye Center
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Eye Institute
state: Ohio
city: Cleveland
country: United States
facility: Cole Eye Institute - Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: Casey Eye Institute, OHSU
state: Oregon
city: Philadelphia
country: United States
facility: The Center for Advanced Retinal & Ocular Therapeutics University of Pennsylvania Perelman School of Medicine
state: Pennsylvania
city: Philadelphia
country: United States
facility: Mid Atlantic Retina
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Bellaire
country: United States
facility: Retina Consultants of Texas
state: Texas
city: Dallas
country: United States
facility: Retina Foundation of the Southwest
state: Texas
city: Houston
country: United States
facility: Baylor Eye Institute
state: Texas
city: San Antonio
country: United States
facility: Retina Consultants of San Antonio Texas
state: Texas
city: Sydney
country: Australia
facility: Sydney Eye Hospital
state: New South Wales
city: East Melbourne
country: Australia
facility: Royal Victorian Eye & Ear Hospital
state: Victoria
city: London
country: United Kingdom
facility: Moorfields Eye Hospital
city: London
country: United Kingdom
facility: The Retina Clinic London, Institute of Ophthalmology, University College London
city: Oxford
country: United Kingdom
facility: Oxford Eye Hospital
Study officials:
affiliation: Beacon Therapeutics
name: Carrie Reichley
role: STUDY_DIRECTOR
References: