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

NCT ID: NCT06275620

Last Updated: 2024-10-30

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-11-14
• Study Completion Date: 2029-12-31

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.

Detailed Description

This is a Phase 2, open-label, multicenter study to evaluate the safety of 2 doses of AGTC-501 administered as a single subretinal injection in participants with XLRP who have previously been treated with a full-length AAV vector-based gene therapy targeting RPGR protein.

The trial includes a screening period of up to 60 days and a 5 year study period.

Each participant will receive a single subretinal injection of one of two dose levels of AGTC-501 in their previously untreated eye. There will be 3 groups. Group 1 will receive the high dose and include up to 12 participants, Group 2 will receive the low dose and will include 6 participants, and Group 3 will include ~3-6 participants. Participants in Groups 1 and 2 will receive the standard corticosteroid regimen. A single subretinal injection of the high dose AGTC-501 will be administered to participants in Group 1 (n = 12), while participants in Group 2 (n = 6) will receive a single subretinal injection of low dose AGTC-501. Group 2 (low dose AGTC-501, Standard Steroid) will be dosed before moving to Group 3. After 6 Group 1 (high dose) study participants reach post-operative Month 1, all data will be reviewed by the DSMC. If no safety signals arise, additional participants, Group 3 (n ~ 3-6), will receive a single subretinal injection of the high dose with a modified course of corticosteroids.

Conditions

X-Linked Retinitis Pigmentosa

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group 1 (High Dose, Standard Corticosteroid)

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.

Group Type: EXPERIMENTAL

AGTC-501 (high dose and standard corticosteroid regimen)

Intervention Type: BIOLOGICAL

Adeno-associated virus vector expressing a human RPGR gene

Group 2 (Low Dose, Standard Corticosteroid)

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.

Group Type: EXPERIMENTAL

AGTC-501 (low dose and standard corticosteroid regimen)

Intervention Type: BIOLOGICAL

Adeno-associated virus vector expressing a human RPGR gene

Group 3 (High Dose, Modified Corticosteroid)

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.

Group Type: EXPERIMENTAL

AGTC-501 (high dose and modified corticosteroid regimen)

Intervention Type: BIOLOGICAL

Adeno-associated virus vector expressing a human RPGR gene

Interventions

AGTC-501 (high dose and standard corticosteroid regimen)

Adeno-associated virus vector expressing a human RPGR gene

Intervention Type: BIOLOGICAL

AGTC-501 (low dose and standard corticosteroid regimen)

Adeno-associated virus vector expressing a human RPGR gene

Intervention Type: BIOLOGICAL

AGTC-501 (high dose and modified corticosteroid regimen)

Adeno-associated virus vector expressing a human RPGR gene

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• 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.

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.
• 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.

• Minimum Eligible Age: 12 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Beacon Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Florida

Jacksonville, Florida, United States

Bascom Palmer Eye Institute

Miami, Florida, United States

Boston Children's Hospital

Boston, Massachusetts, United States

Cincinnati Eye Institute

Cincinnati, Ohio, United States

Cleveland Clinic

Cleveland, Ohio, United States

Casey Eye Institute

Portland, Oregon, United States

Retina Foundation of the Southwest

Dallas, Texas, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 40547876 (View on PubMed)

Other Identifiers

AGTC-RPGR-001 DAWN

Identifier Type: -

Identifier Source: org_study_id