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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

Tracking Information
First Submitted Date  ICMJE October 10, 2017
First Posted Date  ICMJE October 20, 2017
Last Update Posted Date July 15, 2021
Actual Study Start Date  ICMJE April 16, 2018
Estimated Primary Completion Date August 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 27, 2021)
  • 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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 17, 2017)
  • Number of participants experiencing adverse events [ Time Frame: Day 0 - Month 36 ]
  • Number of participants experiencing abnormal clinically relevant hematology/clinical chemistry parameters [ Time Frame: Day 0 - Month 36 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 27, 2021)
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 17, 2017)
  • Changes from baseline in visual function by perimetry [ Time Frame: Day 0 - Month 36 ]
  • Changes from baseline in visual acuity by ETDRS [ Time Frame: Day 0 - Month 36 ]
  • Changes from baseline in retinal structure by OCT [ Time Frame: Day 0 - Month 36 ]
  • Changes from baseline in VFQ-25 quality of life questionnaire [ Time Frame: Day 0 - Month 36 ]
Current Other Pre-specified Outcome Measures
 (submitted: June 15, 2021)
  • 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.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of rAAV2tYF-GRK1-RPGR in Subjects With X-linked Retinitis Pigmentosa Caused by RPGR Mutations
Official Title  ICMJE 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
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE 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
Condition  ICMJE X-Linked Retinitis Pigmentosa
Intervention  ICMJE Biological: rAAV2tYF-GRK1-RPGR
Adeno-associated virus vector expressing a human RPGR gene
Study Arms  ICMJE
  • 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.
    Intervention: Biological: rAAV2tYF-GRK1-RPGR
  • 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.

    Intervention: Biological: rAAV2tYF-GRK1-RPGR
  • 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.
    Intervention: Biological: rAAV2tYF-GRK1-RPGR
  • 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.

    Intervention: Biological: rAAV2tYF-GRK1-RPGR
  • 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.
    Intervention: Biological: rAAV2tYF-GRK1-RPGR
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 27, 2021)		 42
Original Estimated Enrollment  ICMJE
 (submitted: October 17, 2017)		 15
Estimated Study Completion Date  ICMJE August 2026
Estimated Primary Completion Date August 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Gender Based Eligibility: Yes
Ages  ICMJE 6 Years to 50 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Serva Health 855-467-2364 ProviderSupport@scenictrials.com
Contact: Jill Dolgin, PharmD 833-770-2862 advocacy@agtc.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03316560
Other Study ID Numbers  ICMJE AGTC-RPGR-001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Applied Genetic Technologies Corp
Study Sponsor  ICMJE Applied Genetic Technologies Corp
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Matthew Feinsod, MD Applied Genetics Technologies Corporation
PRS Account Applied Genetic Technologies Corp
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP