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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 : July 15, 2021
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
X-Linked Retinitis Pigmentosa Biological: rAAV2tYF-GRK1-RPGR Phase 1 Phase 2

Detailed Description:

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.

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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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
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.
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




Primary Outcome Measures :
  1. Phase 1/2 Dose Escalation: Number and proportion of Adverse Events [ Time Frame: Day 0 - Month 36 ]
  2. 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 ]
  3. 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 ]

Secondary Outcome Measures :
  1. 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 ]
  2. Phase 1/2 Dose Escalation: Changes from baseline in visual acuity [ Time Frame: Day 0 - Month 36 ]
  3. 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 ]
  4. Phase 1/2 Dose Escalation: Changes from baseline in quality of life questionnaire responses [ Time Frame: Day 0 - Month 36 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. 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 ]
  9. Phase 2 Dose Expansion: Changes from baseline in quality of life questionnaire responses [ Time Frame: Day 0 - Month 12 ]

Other Outcome Measures:
  1. Phase 1/2 Dose Escalation: Number and proportion of treatment-emergent adverse events [ Time Frame: Day 0 - Month 36 ]
  2. 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 ]
  3. 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.



Information from the National Library of Medicine

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.


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Ages Eligible for Study:   6 Years to 50 Years   (Child, Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

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


Information from the National Library of Medicine

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


Contacts
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Contact: Serva Health 855-467-2364 ProviderSupport@scenictrials.com
Contact: Jill Dolgin, PharmD 833-770-2862 advocacy@agtc.com

Locations
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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
Sponsors and Collaborators
Applied Genetic Technologies Corp
Investigators
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Study Director: Matthew Feinsod, MD Applied Genetics Technologies Corporation
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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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Applied Genetic Technologies Corp:
XLRP
retinal degeneration
RPGR
adeno-associated virus
gene therapy
AAV
Additional relevant MeSH terms:
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Retinitis
Retinitis Pigmentosa
Retinal Diseases
Eye Diseases
Eye Diseases, Hereditary
Retinal Dystrophies
Retinal Degeneration
Genetic Diseases, Inborn