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A Clinical Trial Evaluating the Safety and Efficacy of a Single Subretinal Injection of AGTC-501 in Participants With X-linked Retinitis Pigmentosa Caused by RPGR Mutations

Primary Purpose

X-Linked Retinitis Pigmentosa

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
rAAV2tYF-GRK1-hRPGRco
Sponsored by
Applied Genetic Technologies Corp
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for X-Linked Retinitis Pigmentosa focused on measuring XLRP, retinal degeneration, RPGR, adeno-associated virus, AAV, gene therapy

Eligibility Criteria

8 Years - 50 Years (Child, Adult)MaleDoes not accept healthy volunteers

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
  • Have a BCVA no better than 75 letters (20/32) and no worse than 35 letters (20/200) in the study eye based on an Early Treatment of Diabetic Retinopathy Study (ETDRS) chart at each screening visit

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Active Comparator

    Active Comparator

    Other

    Arm Label

    Group 1: Low Dose

    Group 2: High Dose

    Group 3: Control

    Arm Description

    Male subjects 8-50 years of age treated by subretinal injection with the low dose of AGTC-501

    Male subjects 8-50 years of age treated by subretinal injection with the high dose of AGTC-501

    Male subjects 8-50 years of age in the untreated control group. Subjects randomized to the untreated control group will be followed for a minimum of 12 months. After this time, they will be treated by subretinal injection with the high dose of AGTC-501.

    Outcomes

    Primary Outcome Measures

    The difference in the proportion of responding eyes between treated and control eyes in low dose group and high dose group

    Secondary Outcome Measures

    - Proportion of responding eyes in treated study eyes in the low dose group and high dose group versus untreated control eyes, as measured by mobility test score change
    - Proportion of responding eyes in treated eyes versus control eyes in the low dose and high dose group measured by visual function assessments
    - Difference in mean change from baseline in Visual Acuity in treated eyes versus control eyes in the low dose and high dose groups
    - Difference in mean change from baseline in the EZ area, as measured by SD-OCT, in treated study eyes in the low dose group and high dose group versus untreated control study eyes
    Changes from baseline in quality of life questionnaire responses

    Full Information

    First Posted
    April 5, 2021
    Last Updated
    May 19, 2021
    Sponsor
    Applied Genetic Technologies Corp
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04850118
    Brief Title
    A Clinical Trial Evaluating the Safety and Efficacy of a Single Subretinal Injection of AGTC-501 in Participants With X-linked Retinitis Pigmentosa Caused by RPGR Mutations
    Official Title
    A Phase 2/3, Randomized, Controlled, Masked, Multi-center Study to Evaluate the Efficacy, Safety and Tolerability of Two Doses of AGTC-501, a Recombinant Adeno-associated Virus Vector Expressing RPGR (rAAV2tYF-GRK1-RPGR), Compared to an Untreated Control Group in Male Subjects With X-linked Retinitis Pigmentosa Confirmed by a Pathogenic Variant in the RPGR Gene
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    May 2021
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    August 2021 (Anticipated)
    Primary Completion Date
    January 2024 (Anticipated)
    Study Completion Date
    March 2029 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Applied Genetic Technologies Corp

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    This study will evaluate and compare the safety, efficacy, and tolerability of 2 doses of a recombinant adeno-associated virus vector (AGTC-501) to an untreated control group in male patients with X-linked retinitis pigmentosa caused by RPGR mutations.
    Detailed Description
    This Phase 2/3 study is a randomized, controlled, masked, multi-center study evaluating and comparing 2 doses of AGTC-501 to an untreated control group. A single subretinal injection of AGTC-501 Dose 1(low dose) or Dose 2(high dose) will be administered in subjects in 2 treatment groups (N=~42), while subjects in the untreated control group (N=~21) will be followed and evaluated up to Month 12, after which they will be eligible to receive treatment with AGTC-501 Dose 2. Approximately 63 eligible male subjects between 8 and 50 years of age (inclusive) will be randomized in a 1:1:1 ratio to 1 of 3 groups (low dose, high dose, untreated control).

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    X-Linked Retinitis Pigmentosa
    Keywords
    XLRP, retinal degeneration, RPGR, adeno-associated virus, AAV, gene therapy

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2, Phase 3
    Interventional Study Model
    Parallel Assignment
    Model Description
    Subjects are randomized in a 1:1:1 ratio to 1 of 3 groups (low dose, high dose, untreated). After 12 months, subjects in the untreated group are eligible to receive the high dose of AGTC-501.
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Masking Description
    For groups 1 and 2 (AGTC-501 dosing groups), both the subjects and the Investigators are masked to dose assignment, and only the unmasked staff who prepare the dose are unmasked to the subject's dose assignment. Due to the need to perform the subretinal injection to administer the study drug, both subjects and Investigators will know whether the subject was assigned to a treatment group or to the control group. To minimize bias of the treated and control study eye evaluations, starting at Month 3, microperimetry, mobility testing, and BCVA assessments will be conducted by appropriately qualified masked evaluators who do not know whether the subject underwent surgery. Subjects will be instructed not to disclose whether they had surgery to the examiner administering the test.
    Allocation
    Randomized
    Enrollment
    63 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Group 1: Low Dose
    Arm Type
    Active Comparator
    Arm Description
    Male subjects 8-50 years of age treated by subretinal injection with the low dose of AGTC-501
    Arm Title
    Group 2: High Dose
    Arm Type
    Active Comparator
    Arm Description
    Male subjects 8-50 years of age treated by subretinal injection with the high dose of AGTC-501
    Arm Title
    Group 3: Control
    Arm Type
    Other
    Arm Description
    Male subjects 8-50 years of age in the untreated control group. Subjects randomized to the untreated control group will be followed for a minimum of 12 months. After this time, they will be treated by subretinal injection with the high dose of AGTC-501.
    Intervention Type
    Biological
    Intervention Name(s)
    rAAV2tYF-GRK1-hRPGRco
    Other Intervention Name(s)
    AGTC-501
    Intervention Description
    Adeno-associated virus vector expressing a human RPGR gene
    Primary Outcome Measure Information:
    Title
    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 Measure Information:
    Title
    - Proportion of responding eyes in treated study eyes in the low dose group and high dose group versus untreated control eyes, as measured by mobility test score change
    Time Frame
    Day 0 - Month 12
    Title
    - Proportion of responding eyes in treated eyes versus control eyes in the low dose and high dose group measured by visual function assessments
    Time Frame
    Day 0 - Month 12
    Title
    - 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
    Title
    - Difference in mean change from baseline in the EZ area, as measured by SD-OCT, in treated study eyes in the low dose group and high dose group versus untreated control study eyes
    Time Frame
    Day 0 - Month 12
    Title
    Changes from baseline in quality of life questionnaire responses
    Time Frame
    Day 0 - Month 12
    Other Pre-specified Outcome Measures:
    Title
    Number and proportion of treatment-emergent adverse events
    Time Frame
    Day 0 - Year 5
    Title
    Number and proportion of participants experiencing abnormal clinically relevant hematology or clinical chemistry parameters
    Time Frame
    Day 0 - Year 5

    10. Eligibility

    Sex
    Male
    Gender Based
    Yes
    Minimum Age & Unit of Time
    8 Years
    Maximum Age & Unit of Time
    50 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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 Have a BCVA no better than 75 letters (20/32) and no worse than 35 letters (20/200) in the study eye based on an Early Treatment of Diabetic Retinopathy Study (ETDRS) chart at each screening visit 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.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Serva Health
    Phone
    855-467-2364
    Email
    ProviderSupport@scenictrials.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Matthew Feinsod, MD
    Organizational Affiliation
    Applied Genetic Technologies Corporation
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

    A Clinical Trial Evaluating the Safety and Efficacy of a Single Subretinal Injection of AGTC-501 in Participants With X-linked Retinitis Pigmentosa Caused by RPGR Mutations

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