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

An Open-Label Dose Escalation Study to Evaluate the Safety and Efficacy of AGTC-501 (rAAV2tYF-GRK1-RPGR) in Subjects With X-linked Retinitis Pigmentosa Caused by RPGR Mutations

Sponsors

Lead Sponsor: Applied Genetic Technologies Corp

Source Applied Genetic Technologies Corp
Brief Summary

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. Approximately 30 participants will be enrolled, and 5 dose levels will be evaluated in a dose-escalation format.

Detailed Description

This will be a non-randomized, open-label, Phase 1/2 dose escalation study.

Approximately 30 participants will be enrolled. 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). Within groups 1 through 3 and 5 and 6, enrollment of participants will be staggered by at least 2 weeks to allow adequate time for review of safety information by the investigators and sponsor. Within Groups 4 and 7, enrollment of the first 3 pediatric participants will be staggered by at least 2 weeks to allow adequate time for review of safety information by the investigators and sponsor. Study agent administration will occur on Day 0. There are a total of 15 visits over approximately 36 months, and long-term follow-up evaluations annually at years 4 and 5.

Safety will be measured by the number and proportion of participants experiencing ocular and non-ocular adverse events or abnormal clinically relevant hematology or clinical chemistry parameters. Efficacy will be measured by evaluation of changes in visual structure, function, and quality of life.

Overall Status Recruiting
Start Date April 16, 2018
Completion Date March 2025
Primary Completion Date March 2023
Phase Phase 1/Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Number of participants experiencing adverse events Day 0 - Month 36
Number of participants experiencing abnormal clinically relevant hematology/clinical chemistry parameters Day 0 - Month 36
Secondary Outcome
Measure Time Frame
Changes from baseline in visual function by perimetry Day 0 - Month 36
Changes from baseline in visual acuity by ETDRS Day 0 - Month 36
Changes from baseline in retinal structure by imaging Day 0 - Month 36
Changes from baseline in quality of life questionnaire Day 0 - Month 36
Enrollment 30
Condition
Intervention

Intervention Type: Biological

Intervention Name: rAAV2tYF-GRK1-RPGR

Description: Adeno-associated virus vector expressing a human RPGR gene

Eligibility

Criteria:

Inclusion Criteria:

- Male subjects with a documented RPGR mutation within exons 1-14 and/or ORF15 from a CLIA-certified laboratory ;

- 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 remaining vision at the intended bleb region;

- Good general health based on a complete physical examination and hematology and clinical chemistry studies performed at a pre-treatment evaluation;

- At least 18 years of age for Groups 1-3, 5 and 6 and at least 6 years of age for Groups 4 and 7;

- Has a parent or caregiver able to follow study instructions, comply with the protocol and attend study visits with the subject as required;

- Signed informed consent and assent (if necessary) obtained before screening.

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);

- Complicating systemic diseases (such as medical conditions causing immunosuppression or known sensitivity or allergy to medications planned for use in the peri-operative period) that would preclude the gene transfer or ocular surgery;

- 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;

- Subjects who are unwilling to use barrier contraception for 3 months following agent administration;

- Any other condition that would prevent a subject from completing follow-up examinations during the course of the study;

- Any other condition that, in the opinion of the investigator, makes the subject unsuitable for the study;

- Current, or recent (the longer of 90 days or 10 half-lives of the drug) participation, in any other research protocol involving investigational agents or therapies;

- Previous receipt of any AAV gene therapy product;

- Study personnel or family members of the study personnel;

- Monocular or having BCVA less than 20/800 in the fellow eye.

Gender: Male

Gender Based: Yes

Minimum Age: 6 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Theresa Heah, MD Study Director Applied Genetics Technologies Corporation
Overall Contact

Last Name: Jill Dolgin, PharmD

Phone: 833-770-2862

Email: [email protected]

Location
Facility: Status:
Colorado Retinal Associates | Golden, Colorado, 80401, United States Not yet recruiting
Boston Children's Hospital | Boston, Massachusetts, 02115, United States Not yet recruiting
Columbia University | New York, New York, 10032, United States Recruiting
Duke Eye Center | Durham, North Carolina, 27701, United States Recruiting
Cincinnati Eye Institute | Cincinnati, Ohio, 45242, United States Recruiting
Cleveland Clinic Foundation | Cleveland, Ohio, 44195, United States Not yet recruiting
Casey Eye Institute, Oregon Health and Sciences University | Portland, Oregon, 97239, United States Recruiting
Wills Eye Hospital | Philadelphia, Pennsylvania, 19107, United States Not yet recruiting
Retina Foundation of the Southwest | Dallas, Texas, 75231, United States Recruiting
Location Countries

United States

Verification Date

May 2019

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 7
Arm Group

Label: Group 1

Type: Experimental

Description: Subjects at least 18 y/o treated with Dose 1 of rAAV2tYF-GRK1-RPGR study drug.

Label: Group 2

Type: Experimental

Description: Subjects at least 18 y/o treated with Dose 2 of rAAV2tYF-GRK1-RPGR study drug.

Label: Group 3

Type: Experimental

Description: Subjects at least 18 y/o treated with Dose 3 of rAAV2tYF-GRK1-RPGR study drug.

Label: Group 4

Type: Experimental

Description: Subjects at least 6 y/o treated with Dose 3 of rAAV2tYF-GRK1-RPGR study drug.

Label: Group 5

Type: Experimental

Description: Subjects at least 18 y/o treated with Dose 5 of rAAV2tYF-GRK1-RPGR study drug.

Label: Group 6

Type: Experimental

Description: Subjects at least 18 y/o treated with Dose 6 of rAAV2tYF-GRK1-RPGR study drug.

Label: Group 7

Type: Experimental

Description: Subjects at least 6 y/o treated with a maximum tolerated dose of rAAV2tYF-GRK1-RPGR study drug determined by Groups 1-6.

Patient Data No
Study Design Info

Allocation: Non-Randomized

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov