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 |
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Recruitment Status :
Recruiting
First Posted : October 20, 2017
Last Update Posted : July 15, 2021
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| 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] and Group 2 [high dose]). Each participant will receive the assigned dose of AGTC-501 in one eye on a single occasion.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 42 participants |
| Allocation: | Randomized |
| Intervention Model: | Single Group Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Masking Description: | Neither the investigator nor the subject will know the dose assignment. Both the subject and the investigator will know which eye received treatment. |
| Primary Purpose: | Treatment |
| 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 Subjects With X-linked Retinitis Pigmentosa Confirmed by a Pathogenic Variant in the RPGR Gene |
| 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 |
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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 |
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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 |
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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 |
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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.
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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: Number and proportion of treatment-emergent 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: 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 between the ages of 6-50 years old 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;
- Also meet the other requirements of the study as specified in the protocol
Phase 1/2 Dose Escalation Exclusion Criteria:
• Have other known retinal disease mutations or previously received an AAV gene therapy product, as well as being unable or unwilling to meet the requirements of the study
Phase 2 Dose Expansion Inclusion Criteria:
- Males between the ages of 8-50 years old with a clinical diagnosis of XLRP with a confirmed RPGR mutation who also meet the other requirements of the study
- 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.
- 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.
Phase 2 Dose Expansion Exclusion Criteria
• Have other known retinal disease mutations or previously received an AAV gene therapy product, as well as being unable or unwilling to meet the requirements of the study
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: Serva Health | 855-467-2364 | ProviderSupport@scenictrials.com | |
| Contact: Jill Dolgin, PharmD | 833-770-2862 | advocacy@agtc.com |
| United States, Florida | |
| University of Florida | Recruiting |
| Jacksonville, Florida, United States, 32209 | |
| United States, Massachusetts | |
| Boston Children's Hospital | 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 | Active, not recruiting |
| Durham, North Carolina, United States, 27701 | |
| United States, Ohio | |
| Cincinnati Eye Institute | Recruiting |
| Cincinnati, Ohio, United States, 45242 | |
| United States, Oregon | |
| Casey Eye Institute, Oregon Health and Science University | Recruiting |
| Portland, Oregon, United States, 97239 | |
| United States, Texas | |
| Retina Foundation of the Southwest | 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: | July 15, 2021 |
| Last Verified: | March 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 |
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XLRP retinal degeneration RPGR |
adeno-associated virus gene therapy AAV |
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Retinitis Retinitis Pigmentosa Retinal Diseases Eye Diseases |
Eye Diseases, Hereditary Retinal Dystrophies Retinal Degeneration Genetic Diseases, Inborn |