A Study Comparing Two Doses of AGTC-501 in Male Participants With X-linked Retinitis Pigmentosa Caused by RPGR Mutations (DAWN)

NCT06275620 | Enrolling By Invitation Phase 2 DMC FDA Drug

• 1 other identifier: AGTC-RPGR-001 DAWN
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 7

Brief Summary

This Phase 2 study is a non-randomized, open-label, study of the safety of AGTC-501 in participants with XLRP who have previously been treated with a full-length AAV vector-based gene therapy targeting RPGR protein.

Conditions

X-Linked Retinitis Pigmentosa

Keywords

XLRP; retinal degeneration; RPGR; adeno-associated virus; gene therapy; AAV

Outcome Measures

Primary Outcomes (2)

• The primary safety outcome is the number of participants experiencing Grade 3 or higher local (ocular) or non-ocular treatment-emergent adverse events, including treatment-emergent serious adverse events (SAEs).

  Day 0 - Month 12

• The primary safety outcome is the proportion of participants experiencing Grade 3 or higher local (ocular) or non-ocular treatment-emergent adverse events, including treatment-emergent serious adverse events (SAEs).

  Day 0 - Month 12

Secondary Outcomes (12)

• The number of participants experiencing treatment-emergent AEs of ocular/non-ocular adverse events, including treatment-emergent serious AEs.

  Day 0 - Month 12

• The proportion of participants experiencing treatment-emergent AEs of ocular/non-ocular adverse events, including treatment-emergent serious AEs.

  Day 0 - Month 12

• Change from baseline in mean sensitivity across the whole grid, as measured by MAIA (Macular Integrity Assessment) microperimetry, assess photoreceptor function under low light

  Day 0 - Month 12

• Response, as measured by MAIA (Macular Integrity Assessment) microperimetry, where response is defined as a greater than or equal to 7 decibel (dB) visual sensitivity improvement from baseline in at least 5 loci.

  Day 0 - Month 12

• Change from baseline in full-field stimulus threshold (FST)

  Day 0 - Month 12

Study Arms (3)

Group 1 (High Dose, Standard Corticosteroid)

EXPERIMENTAL

Following a pars plana vitrectomy, the previously untreated eye of participants (n=up to 12) will receive a central subretinal injection at the high dose in the study eye at the Baseline visit; no treatment will be administered in the previously treated fellow eye. The corticosteroid taper for all treated participants in Groups 1 and 2 (high and low doses with standard corticosteroid regimen) will be a standard taper over the course of several weeks.

Biological: AGTC-501 (high dose and standard corticosteroid regimen)

Group 2 (Low Dose, Standard Corticosteroid)

EXPERIMENTAL

Following a pars plana vitrectomy, the previously untreated eye of participants (n=6) will receive a central subretinal injection at the low dose in the study eye at the Baseline visit; no treatment will be administered in the previously treated fellow eye. The corticosteroid taper for all treated participants in Groups 1 and 2 (high and low doses with standard corticosteroid regimen) will be a standard taper over the course of several weeks.

Biological: AGTC-501 (low dose and standard corticosteroid regimen)

Group 3 (High Dose, Modified Corticosteroid)

EXPERIMENTAL

Following a pars plana vitrectomy, the previously untreated eye of participants (n=approximately 3-6) will receive a central subretinal injection at the high dose in the study eye at the Baseline visit; no treatment will be administered in the previously treated fellow eye. Participants in Group 3 (high dose, modified corticosteroid) will have a more rapid corticosteroid taper.

Biological: AGTC-501 (high dose and modified corticosteroid regimen)

Interventions

AGTC-501 (high dose and standard corticosteroid regimen) BIOLOGICAL

Adeno-associated virus vector expressing a human RPGR gene

Group 1 (High Dose, Standard Corticosteroid)

AGTC-501 (low dose and standard corticosteroid regimen) BIOLOGICAL

Adeno-associated virus vector expressing a human RPGR gene

Group 2 (Low Dose, Standard Corticosteroid)

AGTC-501 (high dose and modified corticosteroid regimen) BIOLOGICAL

Adeno-associated virus vector expressing a human RPGR gene

Group 3 (High Dose, Modified Corticosteroid)

Eligibility Criteria

• Age: 12 Years+
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Be ≥12 years of age
• Have one eye previously treated with an AAV vector-based gene therapy designed to provide full-length functioning RPGR protein.
• Have a BCVA no better than 78 letters and no worse than 34 letters
• Be able to perform all tests of visual and retinal function and structure in both eyes based on the participant's reliability and fixation, per the Investigator's discretion.
• Have detectable baseline mean macular sensitivity measured by MAIA microperimetry, as determined by the Investigator and confirmed by the Central Reading Center (CRC).
• Have detectable EZ line in the study eye as assessed by SD-OCT and confirmed by the CRC.

You may not qualify if:

• 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.
• Have pre-existing eye conditions that would preclude the planned surgery, interfere with the interpretation of study endpoints, or increase the risk of surgical complications
• Had intraocular surgery within 90 days of study treatment administration.
• Have any active ocular/intraocular infection or inflammation
• Have a history of steroid-induced raised IOP of \>25 mmHg following corticosteroid exposure, despite topical IOP-lowering pharmacologic therapy.

Sponsors & Collaborators

• Beacon Therapeutics: lead

Study Sites (7)

University of Florida

Jacksonville, Florida, 32209, United States

Location

Bascom Palmer Eye Institute

Miami, Florida, 33136, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Cincinnati Eye Institute

Cincinnati, Ohio, 45242, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Casey Eye Institute

Portland, Oregon, 97239, United States

Location

Retina Foundation of the Southwest

Dallas, Texas, 75231, United States

Location

Related Publications (1)

• Wang CY, Chen L, Lin TY, Huang SP. Systematic Identification of Candidate Genes for Inherited Retinal Disease Gene Therapy Integrating Worldwide IRD Cohort and Single-Cell Analysis. J Ophthalmol. 2025 Jun 12;2025:7014745. doi: 10.1155/joph/7014745. eCollection 2025.

  PMID: 40547876 DERIVED

MeSH Terms

Conditions

Retinal Degeneration

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Retinal Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2024
• First Posted: February 23, 2024
• Study Start: November 14, 2023
• Primary Completion: November 1, 2025
• Study Completion (Estimated): December 1, 2029
• Last Updated: October 30, 2024

Record last verified: 2024-10

Locations

US (7)