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
Overview
- Phase
- Phase 2
- Intervention
- rAAV2tYF-GRK1-hRPGRco
- Conditions
- X-Linked Retinitis Pigmentosa
- Sponsor
- Beacon Therapeutics
- Enrollment
- 85
- Locations
- 24
- Primary Endpoint
- The proportion of participants with a ≥15 letter increase from baseline in LLVA
- Status
- Active, not recruiting
- Last Updated
- 9 months ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
- •Be between 12 and 50 years of age (inclusive) at the time of informed consent and assent (as applicable).
- •Be male (XY chromosome) and have at least one documented pathogenic or likely pathogenic variant in the RPGR gene.
- •Have a clinical diagnosis of XLRP.
- •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):
- •Have a BCVA ≤ 78 letters (approximately Snellen, 20/32) and ≥ 34 letters (approximately Snellen, 20/200)
- •Have a LLVA ≤64 letters (approximately Snellen 20/50) in the study eye
- •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.
- •Have an LLD of \> 10 letters in the study eye
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.
- •For participants with herpes simplex virus (HSV):
- •Have history of oral or genital herpes and unable and/or unwilling to utilize prophylactic antiviral medication.
- •Have a history of ocular herpes.
- •Have active oral or genital herpes or are currently receiving treatment for HSV infection.
- •Have known sensitivity or allergy to systemic corticosteroids or other immunosuppressive medications.
- •Have used anti-coagulant agents that may alter coagulation
- •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
- •If sexually active or planning to become sexually active, are unwilling to use barrier contraception for 3 months following treatment administration.
- •Are currently participating or recently participated in any other research
Arms & Interventions
Group 1: Dose
Male participants 12-50 years of age treated by subretinal injection with the of AGTC-501
Intervention: rAAV2tYF-GRK1-hRPGRco
Group 2: Dose
Male participants 12-50 years of age treated by subretinal injection with the dose of AGTC-501
Intervention: rAAV2tYF-GRK1-hRPGRco
Group 3: Control
Male participants 12-50 years of age in the untreated control group. Participants in the control group will be followed for a minimum of 24 months. After all participants have reached Month 12, participants in the control group will be given the option to receive the study drug in the fellow eye, if eligible.
Intervention: Control
Outcomes
Primary Outcomes
The proportion of participants with a ≥15 letter increase from baseline in LLVA
Time Frame: Day 0 - Month 12
LLVA(Low Luminance Visual Acuity) will be determined by adding a neutral density filter to the refraction using standard ETDRS (Early Treatment of Diabetic Retinopathy) visual acuity or tumbling "E" chart
Secondary Outcomes
- Change from baseline in LLVA (First Key Secondary Endpoint)(Day 0 - Month 12)
- Change from baseline in mean sensitivity across the whole grid, as measured by MAIA (Second Key Secondary Endpoint) microperimetry(Day 0 - Month 12)
- Change from baseline in full-field stimulus threshold (FST) (Third Key Secondary Endpoint)(Day 0 - Month 12)