A Clinical Trial Evaluating the Safety and Efficacy of a Single Subretinal Injection of AGTC-501 in Participants With XLRP

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

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

Study Overview

• Status: Recruiting
• Conditions: X-Linked Retinitis Pigmentosa
• Intervention / Treatment: Biological: rAAV2tYF-GRK1-hRPGRco; Drug: Control

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.

• Study Type: Interventional
• Enrollment (Estimated): 75
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Serva Health; Phone Number: 855-467-2364; Email: ProviderSupport@scenictrials.com

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32209
      • Recruiting
      • University of Florida Health Jacksonville, Department of Ophthalmology
      • Contact: Shabbir Hamdani; Phone Number: 904-244-9305; Email: ghulam.hamdani@jax.ufl.edu
      • Principal Investigator: Sandeep Grover, MD
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Recruiting
      • Cincinnati Eye Institute
      • Contact: Noah Wendt; Phone Number: 513-569-3479; Email: nwendt@cvphealth.com
      • Principal Investigator: Robert Sisk, MD
  • Texas
    • Dallas, Texas, United States, 75231
      • Recruiting
      • Retina Foundation of the Southwest
      • Contact: Kirsten Locke; Phone Number: 114 214-363-3911; Email: kglocke@retinafoundation.org
      • Principal Investigator: David Birch, Ph.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 50 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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 detectable baseline mean macular sensitivity .
10. Have a detectable sub-foveal ellipsoid zone (EZ) line as assessed by SD-OCT in the study eye and confirmed by the CRC.
11. If study eye will be at the discretion of the Investigator and/or Surgeon.

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 (e.g., warfarin, heparin, apixaban, or high dose docosahexaenoic acid [DHA; fish oil]) within 7 days prior to study treatment administration (ibuprofen, aspirin, or similar are acceptable).
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 and mucosa such as Symbicort (budesonide/formoterol), Flonase (fluticasone propionate), and skin creams and ointments containing corticosteroids shall not be exclusionary.
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 (e.g., severe blepharitis, infectious conjunctivitis, keratitis, scleritis, endophthalmitis, idiopathic or autoimmune associated uveitis, or herpetic lesions).
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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group 1: Dose; Male participants 12-50 years of age treated by subretinal injection with the of AGTC-501	Biological: rAAV2tYF-GRK1-hRPGRco; Adeno-associated virus vector expressing a human RPGR gene; Other Names: AGTC-501
Active Comparator: Group 2: Dose; Male participants 12-50 years of age treated by subretinal injection with the dose of AGTC-501	Biological: rAAV2tYF-GRK1-hRPGRco; Adeno-associated virus vector expressing a human RPGR gene; Other Names: AGTC-501
Other: 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.	Drug: Control; Untreated Control Group 3; Other Names: Untreated Control Group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of participants with a ≥15 letter increase from baseline in LLVA	LLVA(Low Luminance Visual Acuity) will be determined using standard ETDRS (Early Treatment of Diabetic Retinopathy) visual acuity or tumbling "E" chart	Day 0 - Month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in mobility test score at Month 12	Functional vision will be assessed using an Ora-VNC mobility course	Day 0 - Month 12
Change from baseline in mean sensitivity across the whole grid, as measured by MAIA microperimetry	As assessed by MAIA (Macular Integrity Assessment) microperimetry - assess photoreceptor function under low-light	Day 0 - Month 18
Visual sensitivity improvement from baseline in at least 5 loci	As measured by MAIA (Macular Integrity Assessment - assess photoreceptor function under low-light) microperimetry, where response is defined as a ≥7 decibel (dB)	Month 12
Change from baseline in mobility test score	As measured by the MObility Standardized Test-Virtual Reality (MOST-VR) mobility course	Month 12
Change from baseline in full-field stimulus threshold (FST)	Full-field stimulus threshold (FST) measures the sensitivity of the visual field by testing for the lowest luminance flash which elicits a visual sensation perceived	Month 12
Change from baseline in mean sensitivity across the central 4 loci	As measured by MAIA (Macular Integrity Assessment) microperimetry; assess photoreceptor function under low-light	Month 12
Proportion of participants with a ≥15 letter increase from baseline	LLVA - (Low Luminance Visual Acuity) will be determined using standard ETDRS (Early Treatment of Diabetic Retinopathy) visual acuity testing or tumbling "E" chart	Month 18 and Month 24
Change in low-luminance deficit (LLD), defined as the difference between BCVA and LLVA	BCVA (Best Corrected Visual Acuity) / LLVA (Low Luminance Visual Acuity) will be determined using standard ETDRS (Early Treatment of Diabetic Retinopathy) visual acuity or tumbling "E" chart	Month 12
Change from baseline in BCVA over time as assessed by an Early Treatment of Diabetic Retinopathy (ETDRS) or Tumbling E chart at Month 12	BCVA (Best Corrected Visual Acuity) as assessed by an Early Treatment of Diabetic Retinopathy (ETDRS) or Tumbling E chart	Month 12
Response by Ora-VNC where response is defined as a mobility test score increase of 2 or more luminance levels at Month 12	As assessed by functional testing, Ora-VNC mobility course	Month 12
Change from baseline in mean sensitivity across the whole grid, as measured by MAIA microperimetry at Month 24	As assessed by MAIA (Macular Integrity Assessment) microperimetry	Month 24
Visual sensitivity improvement from baseline in at least 5 loci	As measured by MAIA (Macular Integrity Assessment) microperimetry, where response is defined as a ≥7 decibel (dB)	Month 18 and 24
Change from baseline in full-field stimulus threshold (FST) at Month 24	As assessed by full-field threshold (FST) ; (FST)measures the sensitivity of the visual field by testing for the lowest luminance flash which elicits a visual sensation perceived	Month 24
Change from baseline in mean sensitivity across the central 4 loci, as measured by MAIA microperimetry, at Month 18 and Month 24	As measured by MAIA ((Macular Integrity Assessment) microperimetry	Month 18 and 24
Proportion of participants with a ≥10 letter increase from baseline in LLVA at Month 12, 18 and 24	LLVA (Low Luminance Visual Acuity) twill be determined using standard ETDRS visual acuity or tumbling "E" chart	Month 12, 18 and 24
Change in low-luminance deficit (LLD), defined as the difference between BCVA and LLVA Month 18 and 24	Defined as the difference between BCVA/LLVA /LLVA ) Low Luminance Visual Acuity) will be determined using standard ETDRS visual acuity or tumbling "E" chart	Month 18 and 24
Change from baseline in BCVA over time as assessed by an Early Treatment of Diabetic Retinopathy (ETDRS) or Tumbling E chart at Month 18 and 24	As assessed by ETDRS or Tumbling E chart.	Month 18 and 24
Change from baseline in mobility test score at Month 18 and 24 as measured by the Ora- VNC mobility course	as assessed by functional assessment Ora-VNC mobility course	Month 18 and 24
Response by Ora-VNC where response is defined as a mobility test score increase of 2 or more luminance levels at Month 18 and 24	As assessed by functional assessment Ora-VNC mobility course	Month 18 and 24

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and proportion of treatment-emergent ocular/non-ocular adverse events	Ocular/non-ocular adverse events are collected the duration of the trial	Day 0 - Year 5

Collaborators and Investigators

• Sponsor: Beacon Therapeutics
• Investigators: Study Director: Carrie Reichley, Beacon Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2024
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): October 1, 2029

Study Registration Dates

• First Submitted: April 5, 2021
• First Submitted That Met QC Criteria: April 14, 2021
• First Posted (Actual): April 20, 2021

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: retinal degeneration; gene therapy; AAV; adeno-associated virus; XLRP; RPGR
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Genetic Diseases, Inborn; Eye Diseases, Hereditary; Retinal Dystrophies; Retinitis; Retinitis Pigmentosa
• Other Study ID Numbers: AGTC-RPGR-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No