Safety and Efficacy of rAAV2tYF-GRK1-RPGR in Subjects With X-linked Retinitis Pigmentosa Caused by RPGR Mutations (HORIZON)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: X-Linked Retinitis Pigmentosa
• Intervention / Treatment: Biological: rAAV2tYF-GRK1-RPGR

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.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jill Dolgin, PharmD; Phone Number: 833-770-2862; Email: advocacy@agtc.com
• Study Contact Backup: Name: Serva Health; Phone Number: 855-467-2364; Email: ProviderSupport@scenictrials.com

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27701
      • Duke University
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Cincinnati Eye Institute
  • Oregon
    • Portland, Oregon, United States, 97239
      • Casey Eye Institute
  • Texas
    • Dallas, Texas, United States, 75231
      • Retina Foundation of the Southwest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 48 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Phase 1/2 Dose Escalation; Male subjects at least 18 y/o treated with Dose 1 of rAAV2tYF-GRK1-RPGR study drug.	Biological: rAAV2tYF-GRK1-RPGR; Adeno-associated virus vector expressing a human RPGR gene
Experimental: Group 3 and Group 4 Phase 1/2 Dose Escalation; Group 3 male subjects at least 18 y/o and Group 4 male subjects at least 6 y/o treated with Dose 3 of rAAV2tYF-GRK1-RPGR study drug.	Biological: rAAV2tYF-GRK1-RPGR; Adeno-associated virus vector expressing a human RPGR gene
Experimental: Group 6 Phase 1/2 Dose Escalation; Male subjects at least 18 y/o treated with Dose 6 of rAAV2tYF-GRK1-RPGR study drug.	Biological: rAAV2tYF-GRK1-RPGR; Adeno-associated virus vector expressing a human RPGR gene
Experimental: Group 2: Phase 1/2 Dose Escalation; Male subjects at least 18 y/o treated with Dose 2 of rAAV2tYF-GRK1-RPGR study drug.	Biological: rAAV2tYF-GRK1-RPGR; Adeno-associated virus vector expressing a human RPGR gene
Experimental: Group 5 Phase 1/2 Dose Escalation; Male subjects at least 18 y/o treated with Dose 5 of rAAV2tYF-GRK1-RPGR study drug.	Biological: rAAV2tYF-GRK1-RPGR; Adeno-associated virus vector expressing a human RPGR gene

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and proportion of Adverse Events	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;	Day 0 - Month 36
Number and proportion of participants experiencing abnormal clinically relevant hematology or clinical chemistry parameters.		Day 0 - Month 36

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes from baseline in visual function as measured by mesopic microperimetry in the treated eye compared to the untreated eye	Day 0 - Month 36
Changes from baseline in visual acuity	Day 0 - Month 36
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
Change from baseline in fundus imaging	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1/2 Dose Escalation: Number and proportion of treatment-emergent adverse events		Day 0 - Month 36
Phase 1/2 Dose Escalation: Number and proportion of participants experiencing abnormal clinically relevant hematology or clinical chemistry parameters		Day 0 - Month 36
Phase 2 Dose Expansion: Overall safety evaluation	The safety evaluation will be based on ophthalmic examinations, AE reporting, laboratory assessments, and physical examinations, as well as any safety information collected as a result of the efficacy assessments, as appropriate.	Day 0 - Month 12

Collaborators and Investigators

• Sponsor: Beacon Therapeutics
• Investigators: Study Director: Matthew Feinsod, MD, Applied Genetics Technologies Corporation

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2018
• Primary Completion (Actual): November 9, 2023
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: October 10, 2017
• First Submitted That Met QC Criteria: October 17, 2017
• First Posted (Actual): October 20, 2017

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 16, 2024
• Last Verified: February 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-001 HORIZON

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