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

Beacon Therapeutics

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: X-Linked Retinitis Pigmentosa

Treatments: Biological: rAAV2tYF-GRK1-RPGR

Study type: Interventional

Funder types: Industry

Identifiers

NCT03316560

AGTC-RPGR-001 HORIZON

Details and patient eligibility

About

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.

Full 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.

Enrollment: 29 patients

Sex: Male

Ages: 6 to 50 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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29 participants in 6 patient groups

Group 1: Phase 1/2 Dose Escalation

Experimental group

Description:

Male subjects at least 18 y/o treated with Dose 1 of rAAV2tYF-GRK1-RPGR study drug.

Treatment:

Biological: rAAV2tYF-GRK1-RPGR

Group 2: Phase 1/2 Dose Escalation

Experimental group

Description:

Male subjects at least 18 y/o treated with Dose 2 of rAAV2tYF-GRK1-RPGR study drug.

Treatment:

Biological: rAAV2tYF-GRK1-RPGR

Group 3 Phase 1/2 Dose Escalation

Experimental group

Description:

Group 3 male subjects at least 18 y/o treated with Dose 3 of rAAV2tYF-GRK1-RPGR study drug.

Treatment:

Biological: rAAV2tYF-GRK1-RPGR

Group 4 Phase 1/2 Dose Escalation

Experimental group

Description:

Group 4 male subjects at least 6 y/o treated with Dose 3 of rAAV2tYF-GRK1-RPGR study drug.

Treatment:

Biological: rAAV2tYF-GRK1-RPGR

Group 5 Phase 1/2 Dose Escalation

Experimental group

Description:

Male subjects at least 18 y/o treated with Dose 5 of rAAV2tYF-GRK1-RPGR study drug.

Treatment:

Biological: rAAV2tYF-GRK1-RPGR

Group 6 Phase 1/2 Dose Escalation

Experimental group

Description:

Male subjects at least 18 y/o treated with Dose 6 of rAAV2tYF-GRK1-RPGR study drug.

Treatment:

Biological: rAAV2tYF-GRK1-RPGR