Safety and Efficacy of rAAV2tYF-GRK1-RPGR in Subjects With X-linked Retinitis Pigmentosa Caused by RPGR Mutations
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ClinicalTrials.gov Identifier: NCT03316560 |
Recruitment Status :
Recruiting
First Posted : October 20, 2017
Last Update Posted : January 29, 2021
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Condition or disease | Intervention/treatment | Phase |
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X-Linked Retinitis Pigmentosa | Biological: rAAV2tYF-GRK1-RPGR | Phase 1 Phase 2 |
This study includes a non-randomized, open-label, Phase 1/2 dose escalation portion, and a Phase 2 randomized, controlled, masked dose expansion portion.
Approximately 30 participants will be enrolled into the dose escalation portion of the study. 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 Group 4, 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.
After the phase 1/2 portion of the study is completed, approximately 12 participants, who were not part of the Phase 1/2 portion of the study, will be enrolled into the dose expansion portion of the study. These participants will be randomized in a 1:1 ratio to 1 of 2 treatment groups (i.e., Group 1 [low dose, 300 μL containing 1.2 x 1011 vg/mL] and Group 2 [high dose, 300 μL containing 1.1 x 1012 vg/mL]). Each participant will receive the assigned dose of AGTC-501 in one eye on a single occasion. Randomization to dose groups will be stratified by age (8-17 years, 18-50 years). To minimize bias in the assessment and reporting of outcomes, both the investigators and the study subjects will be masked to the dose of AGTC-501 received. Study agent administration will occur on Day 0. There are a total of 15 visits over approximately 24 months, and long-term follow-up evaluations annually at years 3, 4 and 5.
Safety will be measured by the number and proportion of participants experiencing ocular and non-ocular adverse events and abnormal clinically relevant hematology and clinical chemistry parameters. Efficacy will be measured by evaluation of changes in visual structure, function, and quality of life.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 42 participants |
Allocation: | Randomized |
Intervention Model: | Single Group Assignment |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Primary Purpose: | Treatment |
Official Title: | 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 |
Actual Study Start Date : | April 16, 2018 |
Estimated Primary Completion Date : | August 2022 |
Estimated Study Completion Date : | August 2026 |

Arm | Intervention/treatment |
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Experimental: Group 1: Phase 1/2 Dose Escalation
Male subjects at least 18 y/o treated with Dose 1 of rAAV2tYF-GRK1-RPGR study drug.
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Biological: rAAV2tYF-GRK1-RPGR
Adeno-associated virus vector expressing a human RPGR gene |
Experimental: Group 2: Phase 1/2 Dose Escalation and Low Dose Group Phase 2 Dose Expansion
Phase 1/2 Dose Escalation: male subjects at least 18 y/o treated with Dose 2 of rAAV2tYF-GRK1-RPGR study drug. Phase 2 Dose Expansion: male subjects at least 8 y/o treated with Dose 2 of rAAV2tYF-GRK1-RPGR study drug. This will be the low dose group for the phase 2 expansion. |
Biological: rAAV2tYF-GRK1-RPGR
Adeno-associated virus vector expressing a human RPGR gene |
Experimental: Group 3 and Group 4 Phase 1/2 Dose Escalation
Group 3 male subjects at least 18 y/o and Group 4 male subjects at least 6 y/o treated with Dose 3 of rAAV2tYF-GRK1-RPGR study drug.
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Biological: rAAV2tYF-GRK1-RPGR
Adeno-associated virus vector expressing a human RPGR gene |
Experimental: Group 5 Phase 1/2 Dose Escalation and High Dose Group Phase 2 Dose Expansion
Phase 1/2 Dose Escalation: male subjects at least 18 y/o treated with Dose 5 of rAAV2tYF-GRK1-RPGR study drug. Phase 2 Dose Expansion: male subjects at least 8 y/o treated with Dose 5 of rAAV2tYF-GRK1-RPGR study drug. This will be the high dose group for the phase 2 expansion. |
Biological: rAAV2tYF-GRK1-RPGR
Adeno-associated virus vector expressing a human RPGR gene |
Experimental: Group 6 Phase 1/2 Dose Escalation
Male subjects at least 18 y/o treated with Dose 6 of rAAV2tYF-GRK1-RPGR study drug.
|
Biological: rAAV2tYF-GRK1-RPGR
Adeno-associated virus vector expressing a human RPGR gene |
- Phase 1/2 Dose Escalation: Number and proportion of Adverse Events [ Time Frame: Day 0 - Month 36 ]
- Phase 1/2 Dose Escalation: Number and proportion of participants experiencing abnormal clinically relevant hematology or clinical chemistry parameters. [ Time Frame: Day 0 - Month 36 ]
- Phase 2 Dose Expansion: The difference in the proportion of responding eyes between treated and control eyes in low dose group and high dose group. [ Time Frame: Day 0 - Month 12 ]
- Phase 1/2 Dose Escalation: Changes from baseline in visual function as measured by mesopic microperimetry in the treated eye compared to the untreated eye [ Time Frame: Day 0 - Month 36 ]
- Phase 1/2 Dose Escalation: Changes from baseline in visual acuity [ Time Frame: Day 0 - Month 36 ]
- Phase 1/2 Dose Escalation: Changes from baseline in retinal structure as assessed by spectral-domain optical coherence tomography (SD-OCT) [ Time Frame: Day 0 - Month 36 ]
- Phase 1/2 Dose Escalation: Changes from baseline in quality of life questionnaire responses [ Time Frame: Day 0 - Month 36 ]
- Phase 2 Dose Expansion: Proportion of responding eyes in treated eyes versus control eyes in the low dose and high dose group measured by mobility test [ Time Frame: Day 0 - Month 12 ]
- Phase 2 Dose Expansion: Proportion of responding eyes in treated eyes versus control eyes in the low dose and high dose group measured by visual function [ Time Frame: Day 0 - Month 12 ]
- Phase 2 Dose Expansion: Difference in mean change from baseline in Visual Acuity in treated eyes versus control eyes in the low dose and high dose groups [ Time Frame: Day 0 - Month 12 ]
- Phase 2 Dose Expansion: Difference in mean change from baseline in the EZ area, as measured by SD-OCT, in treated eyes versus control eyes in the low dose group and high dose group [ Time Frame: Day 0 - Month 12 ]
- Phase 2 Dose Expansion: Changes from baseline in quality of life questionnaire responses [ Time Frame: Day 0 - Month 12 ]
- Phase 1/2 Dose Escalation: Changes in antibody and T-cell responses to AAV and RPGR as measured quantitatively and by frequency of positive responses [ Time Frame: Day 0 - Month 36 ]
- Phase 1/2 Dose Escalation: Presence of vector DNA and blood by qPCR assay [ Time Frame: Day 0 - Month 36 ]
- Phase 2 Dose Expansion: Overall safety evaluation [ Time Frame: Day 0 - Month 12 ]The safety evaluation will be based on ophthalmic examinations, AE reporting, laboratory assessments, and physical examinations, as well as any safety information collected as a result of the efficacy assessments, as appropriate.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 6 Years to 50 Years (Child, Adult) |
Sexes Eligible for Study: | Male |
Gender Based Eligibility: | Yes |
Accepts Healthy Volunteers: | No |
Phase 1/2 Dose Escalation Inclusion Criteria:
- Male subjects with a documented RPGR mutation within exons 1-14 and/or ORF15 from a Clinical Laboratory Improvement Amendments (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 baseline mean macular sensitivity between 1-2 dB in both eyes, as measured by Microperimetry;
- 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.
- 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);
- 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 or reason 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.
Phase 2 Dose Expansion Inclusion Criteria:
- Provide written informed consent or assent (per local regulation), prior to the conduct of any study-related procedure. Subjects who provide assent must have a parent, guardian, or legal representative provide written informed consent.
- Be between 8 and 50 years of age (inclusive) at the time of informed consent and assent (as applicable).
- Be male and have at least one documented pathogenic or likely pathogenic variant in the RPGR gene within exons 1-14 and/or ORF15 from Molecular Vision Laboratory (MVL), a CLIA-certified laboratory.
- Have a clinical diagnosis of XLRP.
- Be in good general health to withstand subretinal surgery and perioperative medications based on a complete physical examination and hematology and clinical chemistry evaluations performed at screening.
- Be able and willing, as assessed by the investigator, to follow study instructions, complete study assessments, comply with the protocol, and attend study visits for the duration of the study.
- If the subject has a parent or caregiver, the parent or caregiver must be able to follow study instructions, comply with the protocol, and attend study visits with the subject, as required.
- Both eyes: Have a BCVA no better than 75 letters (20/32) and no worse than 35 letters (20/200) in both eyes based on an ETDRS chart at each screening visit. Pediatric subjects unable to read the ETDRS letters may utilize a tumbling "E" chart for BCVA assessments.
- Both eyes: Be able to perform all tests of visual and retinal function and structure based on the subject's reliability, and fixation, per the investigator's discretion.
- Both eyes: Have detectable baseline mean macular sensitivity measured by (MAIA) microperimetry, between 1-12 dB, as determined by the investigator and confirmed by the Central Reading Center (CRC), at each screening visit.
- Both eyes: Have detectable EZ line as assessed by SD-OCT and confirmed by the CRC.
Phase 2 Dose Expansion Exclusion Criteria
- Have other known disease-causing mutations documented in the subject'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.
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For subjects with herpes simplex virus (HSV):
- Have history of oral or genital herpes and unable and/or unwilling to utilize prophylactic antiviral medication.
- Have a history of ocular herpes.
- Have active oral or genital herpes, or are currently receiving treatment for HSV infection.
- Have complicating systemic diseases (e.g., medical conditions causing immunosuppression, active systemic infection) that would preclude the gene transfer or ocular surgery.
- Have known sensitivity or allergy to systemic corticosteroids or other immunosuppressive medications.
- Have used anti-coagulant agents that may alter coagulation (e.g., warfarin, heparin, apixaban, or high dose DHA [fish oil]) within 7 days prior to study treatment administration (ibuprofen, aspirin, or similar are acceptable).
- Have received any vaccination/immunization within 28 days prior to screening and/or during screening with the exception of the influenza vaccine. Subjects should be excluded if they have received the influenza vaccine within 28 days prior to randomization.
- Have used systemic corticosteroids or other immunosuppressive medications within 3 months prior to screening and/or intend to use during screening.
- If sexually active or planning to become sexually active, are unwilling to use barrier contraception for 3 months following treatment administration.
- Have any other condition or reason that, in the opinion of both the Medical Monitor and the investigator, would prevent a subject from completing study assessments during the course of the study.
- Have any other condition or reason that, in the opinion of both the Medical Monitor and the investigator, makes the subject unsuitable for the study.
- Are currently participating or recently participated in any other research protocol involving investigational agents or therapies, in the opinion of both the Medical Monitor and the investigator, would make the subject unsuitable for the study. Recent participation is defined as participation within 90 days of initial screening for this study OR within 10 half-lives of the investigational drug, whichever is longer.
- Have previously received any AAV gene therapy product, stem cell therapy, cell-based therapy, or similar biologics.
- Either Eye: 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 (e.g., corneal opacities, diabetic retinopathy, retinal vasculitis, glaucoma).
- Either Eye: Have significant media opacity impacting evaluation of the retina or vitreous. This includes cataracts considered to be a major contributor to reducing visual acuity and/or if the subject is likely to require cataract extraction within 3 months of study treatment administration.
- Either Eye: Had intraocular surgery within 90 days of study treatment administration.
- Either Eye: Have any active ocular/intraocular infection or inflammation (e.g., severe blepharitis, infectious conjunctivitis, keratitis, scleritis, endophthalmitis, idiopathic or autoimmuneassociated uveitis, or herpetic lesions).
- Either Eye: Have a history of steroid-induced raised IOP of >25 mmHg following corticosteroid exposure, despite topical IOP-lowering pharmacologic therapy.
- Either Eye: Have any artificial retinal implant or prosthesis.
- Either Eye: Have highly variable baseline mean macular sensitivity of >2 dB between any of the 3 microperimetry assessments performed during screening.
- Either Eye: Have absence of clear ocular media and/or inadequate pupil dilation to facilitate good quality OCT images.
- Either Eye: Have any history of rhegmatogenous retinal detachment.
- Either Eye: Have spherical equivalent > -10 diopters (D) of myopia, or absolute axial length beyond 30 mm at the investigator's or surgeon's discretion.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03316560
Contact: Jill Dolgin, PharmD | 833-770-2862 | advocacy@agtc.com |
United States, Florida | |
University of Florida | Not yet recruiting |
Jacksonville, Florida, United States, 32209 | |
United States, Massachusetts | |
Boston Children's Hospital | Not yet recruiting |
Boston, Massachusetts, United States, 02115 | |
United States, New York | |
Columbia University | Withdrawn |
New York, New York, United States, 10032 | |
United States, North Carolina | |
Duke Eye Center | Not yet recruiting |
Durham, North Carolina, United States, 27701 | |
United States, Ohio | |
Cincinnati Eye Institute | Recruiting |
Cincinnati, Ohio, United States, 45242 | |
Cleveland Clinic Foundation | Not yet recruiting |
Cleveland, Ohio, United States, 44195 | |
United States, Oregon | |
Casey Eye Institute, Oregon Health and Sciences University | Not yet recruiting |
Portland, Oregon, United States, 97239 | |
United States, Pennsylvania | |
Wills Eye Hospital | Not yet recruiting |
Philadelphia, Pennsylvania, United States, 19107 | |
United States, Texas | |
Retina Foundation of the Southwest | Not yet recruiting |
Dallas, Texas, United States, 75231 |
Study Director: | Matthew Feinsod, MD | Applied Genetics Technologies Corporation |
Responsible Party: | Applied Genetic Technologies Corp |
ClinicalTrials.gov Identifier: | NCT03316560 |
Other Study ID Numbers: |
AGTC-RPGR-001 |
First Posted: | October 20, 2017 Key Record Dates |
Last Update Posted: | January 29, 2021 |
Last Verified: | January 2021 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
XLRP retinal degeneration RPGR |
adeno-associated virus gene therapy AAV |
Retinitis Retinitis Pigmentosa Retinal Diseases Eye Diseases |
Eye Diseases, Hereditary Retinal Dystrophies Retinal Degeneration Genetic Diseases, Inborn |