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Safety and Efficacy of rAAV2tYF-GRK1-RPGR in Subjects With X-linked Retinitis Pigmentosa Caused by RPGR Mutations

Primary Purpose

X-Linked Retinitis Pigmentosa

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
rAAV2tYF-GRK1-RPGR
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, gene therapy, AAV

Eligibility Criteria

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

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

Sites / Locations

  • University of FloridaRecruiting
  • Boston Children's HospitalRecruiting
  • Columbia University
  • Duke Eye Center
  • Cincinnati Eye InstituteRecruiting
  • Casey Eye Institute, Oregon Health and Science UniversityRecruiting
  • Retina Foundation of the SouthwestRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Group 1: Phase 1/2 Dose Escalation

Group 2: Phase 1/2 Dose Escalation and Low Dose Group Phase 2 Dose Expansion

Group 3 and Group 4 Phase 1/2 Dose Escalation

Group 5 Phase 1/2 Dose Escalation and High Dose Group Phase 2 Dose Expansion

Group 6 Phase 1/2 Dose Escalation

Arm Description

Male subjects at least 18 y/o treated with Dose 1 of rAAV2tYF-GRK1-RPGR study drug.

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.

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.

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.

Male subjects at least 18 y/o treated with Dose 6 of rAAV2tYF-GRK1-RPGR study drug.

Outcomes

Primary Outcome Measures

Phase 1/2 Dose Escalation: Number and proportion of Adverse Events
Phase 1/2 Dose Escalation: Number and proportion of participants experiencing abnormal clinically relevant hematology or clinical chemistry parameters.
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.

Secondary Outcome Measures

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
Phase 1/2 Dose Escalation: Changes from baseline in visual acuity
Phase 1/2 Dose Escalation: Changes from baseline in retinal structure as assessed by spectral-domain optical coherence tomography (SD-OCT)
Phase 1/2 Dose Escalation: Changes from baseline in quality of life questionnaire responses
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
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
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
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
Phase 2 Dose Expansion: Changes from baseline in quality of life questionnaire responses

Full Information

First Posted
October 10, 2017
Last Updated
July 13, 2021
Sponsor
Applied Genetic Technologies Corp
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1. Study Identification

Unique Protocol Identification Number
NCT03316560
Brief Title
Safety and Efficacy of rAAV2tYF-GRK1-RPGR in Subjects With X-linked Retinitis Pigmentosa Caused by RPGR Mutations
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2021
Overall Recruitment Status
Recruiting
Study Start Date
April 16, 2018 (Actual)
Primary Completion Date
August 2022 (Anticipated)
Study Completion Date
August 2026 (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 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.

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, gene therapy, AAV

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes 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.
Allocation
Randomized
Enrollment
42 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Group 1: Phase 1/2 Dose Escalation
Arm Type
Experimental
Arm Description
Male subjects at least 18 y/o treated with Dose 1 of rAAV2tYF-GRK1-RPGR study drug.
Arm Title
Group 2: Phase 1/2 Dose Escalation and Low Dose Group Phase 2 Dose Expansion
Arm Type
Experimental
Arm Description
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.
Arm Title
Group 3 and Group 4 Phase 1/2 Dose Escalation
Arm Type
Experimental
Arm Description
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.
Arm Title
Group 5 Phase 1/2 Dose Escalation and High Dose Group Phase 2 Dose Expansion
Arm Type
Experimental
Arm Description
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.
Arm Title
Group 6 Phase 1/2 Dose Escalation
Arm Type
Experimental
Arm Description
Male subjects at least 18 y/o treated with Dose 6 of rAAV2tYF-GRK1-RPGR study drug.
Intervention Type
Biological
Intervention Name(s)
rAAV2tYF-GRK1-RPGR
Intervention Description
Adeno-associated virus vector expressing a human RPGR gene
Primary Outcome Measure Information:
Title
Phase 1/2 Dose Escalation: Number and proportion of Adverse Events
Time Frame
Day 0 - Month 36
Title
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
Title
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 Measure Information:
Title
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
Title
Phase 1/2 Dose Escalation: Changes from baseline in visual acuity
Time Frame
Day 0 - Month 36
Title
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
Title
Phase 1/2 Dose Escalation: Changes from baseline in quality of life questionnaire responses
Time Frame
Day 0 - Month 36
Title
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
Title
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
Title
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
Title
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
Title
Phase 2 Dose Expansion: Changes from baseline in quality of life questionnaire responses
Time Frame
Day 0 - Month 12
Other Pre-specified Outcome Measures:
Title
Phase 1/2 Dose Escalation: Number and proportion of treatment-emergent adverse events
Time Frame
Day 0 - Month 36
Title
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
Title
Phase 2 Dose Expansion: Overall safety evaluation
Description
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.
Time Frame
Day 0 - Month 12

10. Eligibility

Sex
Male
Gender Based
Yes
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Serva Health
Phone
855-467-2364
Email
ProviderSupport@scenictrials.com
First Name & Middle Initial & Last Name or Official Title & Degree
Jill Dolgin, PharmD
Phone
833-770-2862
Email
advocacy@agtc.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Matthew Feinsod, MD
Organizational Affiliation
Applied Genetics Technologies Corporation
Official's Role
Study Director
Facility Information:
Facility Name
University of Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32209
Country
United States
Individual Site Status
Recruiting
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Name
Columbia University
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Individual Site Status
Withdrawn
Facility Name
Duke Eye Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27701
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Cincinnati Eye Institute
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45242
Country
United States
Individual Site Status
Recruiting
Facility Name
Casey Eye Institute, Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Individual Site Status
Recruiting
Facility Name
Retina Foundation of the Southwest
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Safety and Efficacy of rAAV2tYF-GRK1-RPGR in Subjects With X-linked Retinitis Pigmentosa Caused by RPGR Mutations

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