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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

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

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

NCT ID

NCT03316560

First Posted

October 10, 2017

Last Updated

July 13, 2021

Sponsor

Applied Genetic Technologies Corp

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

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

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

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

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

ProviderSupport@scenictrials.com

First Name & Middle Initial & Last Name or Official Title & Degree

Jill Dolgin, PharmD

Phone

833-770-2862

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

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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