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

X-Linked Retinitis Pigmentosa Clinical Trial

Official title:

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 Participants With X-linked Retinitis Pigmentosa

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT06275620
• Other study ID #: AGTC-RPGR-001 DAWN
• Status: Enrolling by invitation
• Phase: Phase 2
• Start date: November 14, 2023
• Est. completion date: August 2029

Study information

• Verified date: March 2024
• Source: Beacon Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 in their previously untreated eye. There will be 2 groups of 6 participants, each receiving one of two doses of the study treatment along with the standard corticosteroid regimen, followed by a third group of ~3-6 participants receiving the high dose but with a modified corticosteroid regimen. The first 6 participants will be enrolled in Group 1, followed by Group 2. Group 3 will open for enrollment after data has been reviewed by the DSMC. DSMC review will occur after all 6 Group 1 (high dose) study participants reach post-operative Month 1 and periodically throughout the study.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 18
• Est. completion date: August 2029
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• Be at least 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.

Related Conditions & MeSH terms

• Retinitis
• Retinitis Pigmentosa
• X-Linked Retinitis Pigmentosa

Intervention

Biological:
• AGTC-501 (high dose and standard corticosteroid regimen)
Adeno-associated virus vector expressing a human RPGR gene
• AGTC-501 (low dose and standard corticosteroid regimen)
Adeno-associated virus vector expressing a human RPGR gene
• AGTC-501 (high dose and modified corticosteroid regimen)
Adeno-associated virus vector expressing a human RPGR gene

Locations

Country	Name	City	State
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Cincinnati Eye Institute	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Retina Foundation of the Southwest	Dallas	Texas
United States	University of Florida	Jacksonville	Florida
United States	Bascom Palmer Eye Institute	Miami	Florida
United States	Casey Eye Institute	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Beacon Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary safety outcome is the number and 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	Change from baseline in mean sensitivity across the whole grid, as measured by MAIA microperimetry		Day 0 - Month 12
Secondary	Response, as measured by MAIA microperimetry, where response is defined as a greater than or equal to 7 dB visual sensitivity improvement from baseline in at least 7 loci.		Day 0 - Month 12
Secondary	Change from baseline in BCVA using Early-Treatment Diabetic Retinopathy Study (ETDRS) visual acuity		Day 0 - Month 12
Secondary	Change from baseline in LLVA using ETDRS visual acuity		Day 0 - Month 12
Secondary	Change from baseline in Ora-VNC mobility test score		Day 0 - Month 12