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Trial record 4 of 8 for:    X-Linked Retinitis Pigmentosa

Safety and Efficacy of rAAV2tYF-GRK1-RPGR in Subjects With X-linked Retinitis Pigmentosa Caused by RPGR-ORF15 Mutations

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ClinicalTrials.gov Identifier: NCT03316560
Recruitment Status : Recruiting
First Posted : October 20, 2017
Last Update Posted : January 4, 2018
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 expressing a human RPGR-ORF15 gene (rAAV2tYF-GRK1-RPGR) in patients with X-linked retinitis pigmentosa caused by RPGR-ORF15 mutations. Approximately 15 participants will be enrolled and 3 dose levels will be evaluated in a dose-escalation format.

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

Detailed Description:

This will be a non-randomized, open-label, Phase 1/2 dose escalation study.

Approximately 15 participants will be enrolled. 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). Participants in the dose escalation phase will be ≥ 18 years of age. After the maximum tolerated dose is identified individuals ≥ 6 years of age will be enrolled.

Safety will be measured by the number and proportion of participants experiencing ocular and non-ocular adverse events or abnormal clinically relevant hematology or clinical chemistry parameters. Efficacy will be measured by evaluation of changes in visual structure, function, and quality of life.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label Dose Escalation Study to Evaluate the Safety and Efficacy of AGTC-501 (rAAV2tYF-GRK1-RPGR) in Subjects With X-linked Retinitis Pigmentosa Caused by RPGR-ORF15 Mutations
Estimated Study Start Date : January 2018
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : January 2024


Arm Intervention/treatment
Experimental: Group 1
Subjects at least 18 y/o treated with a lower dose of rAAV2tYF-GRK1-RPGR study drug.
Biological: rAAV2tYF-GRK1-RPGR
Adeno-associated virus vector expressing a human RPGR-ORF15 gene

Experimental: Group 2
Subjects at least 18 y/o treated with a middle dose of rAAV2tYF-GRK1-RPGR study drug.
Biological: rAAV2tYF-GRK1-RPGR
Adeno-associated virus vector expressing a human RPGR-ORF15 gene

Experimental: Group 3
Subjects at least 18 y/o treated with a higher dose of rAAV2tYF-GRK1-RPGR study drug.
Biological: rAAV2tYF-GRK1-RPGR
Adeno-associated virus vector expressing a human RPGR-ORF15 gene

Experimental: Group 4
Subjects at least 6 y/o treated with a maximum tolerated dose of rAAV2tYF-GRK1-RPGR study drug determined for Groups 1, 2 and 3.
Biological: rAAV2tYF-GRK1-RPGR
Adeno-associated virus vector expressing a human RPGR-ORF15 gene




Primary Outcome Measures :
  1. Number of participants experiencing adverse events [ Time Frame: Day 0 - Month 36 ]
  2. Number of participants experiencing abnormal clinically relevant hematology/clinical chemistry parameters [ Time Frame: Day 0 - Month 36 ]

Secondary Outcome Measures :
  1. Changes from baseline in visual function by perimetry [ Time Frame: Day 0 - Month 36 ]
  2. Changes from baseline in visual acuity by ETDRS [ Time Frame: Day 0 - Month 36 ]
  3. Changes from baseline in retinal structure by OCT [ Time Frame: Day 0 - Month 36 ]
  4. Changes from baseline in VFQ-25 quality of life questionnaire [ Time Frame: Day 0 - Month 36 ]


Information from the National Library of Medicine

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

Inclusion Criteria:

  • Male subjects with the clinical diagnosis of X-linked retinitis pigmentosa (XLRP) and a documented molecular diagnosis from a CLIA-certified laboratory of mutation within the ORF15 exon of the RPGR gene;
  • Best-corrected visual acuity of 20/50 (65 ETDRS letters) or worse in the study eye for Groups 1-3; and best-corrected visual acuity of 20/32 (75 ETDRS letters) or worse in the study eye for Group 4;
  • Ability to perform tests of visual and retinal function and structure and ability to comply with other research procedures;
  • Detectable remaining vision at the intended bleb region;
  • Good general health based on a complete physical examination and hematology and clinical chemistry studies performed at a pre-treatment evaluation;
  • At least 18 years of age for Groups 1, 2 and 3 and at least 6 years of age for Group 4;
  • Has a parent or caregiver able to follow study instructions, comply with the protocol and attend study visits with the subject as required;
  • Signed informed consent and assent (if necessary) obtained before screening.

Exclusion Criteria:

  • Pre-existing eye conditions that would preclude the planned surgery or interfere with the interpretation of study endpoints or increase the risk of surgical complications (for example, glaucoma, corneal or lenticular opacities, diabetic retinopathy, retinal vasculitis);
  • Complicating systemic diseases (such as medical conditions causing immunosuppression or known sensitivity or allergy to medications planned for use in the peri-operative period) that would preclude the gene transfer or ocular surgery;
  • Use of anti-coagulant agents that may alter coagulation within 7 days prior to study agent administration;
  • Use of systemic corticosteroids or other immunosuppressive medications within 3 months prior to enrollment;
  • Males who are unwilling to use barrier contraception for 3 months following agent administration;
  • Any other condition that would prevent a subject from completing follow-up examinations during the course of the study;
  • Any other condition that, in the opinion of the investigator, makes the subject unsuitable for the study;
  • Current, or recent (the longer of 90 days or 10 half-lives of the drug) participation, in any other research protocol involving investigational agents or therapies;
  • Previous receipt of any AAV gene therapy product;
  • Study personnel or family members of the study personnel;
  • Monocular or having BCVA less than 20/800 in the fellow eye.

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
Contact: Jill Dolgin, PharmD advocacy@agtc.com

Locations
United States, North Carolina
Duke Eye Center Not yet recruiting
Durham, North Carolina, United States, 27701
United States, Oregon
Casey Eye Institute, Oregon Health and Sciences University Recruiting
Portland, Oregon, United States, 97239
United States, Pennsylvania
University of Pennsylvania Scheie Eye Institute Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Wills Eye Hospital Not yet recruiting
Philadelphia, Pennsylvania, United States, 19107
United States, Texas
Retina Foundation of the Southwest Recruiting
Dallas, Texas, United States, 75231
Sponsors and Collaborators
Applied Genetic Technologies Corp
Investigators
Study Director: Matt Feinsod, MD Applied Genetics Technologies Corporation

Responsible Party: Applied Genetic Technologies Corp
ClinicalTrials.gov Identifier: NCT03316560     History of Changes
Other Study ID Numbers: AGTC-RPGR-001
First Posted: October 20, 2017    Key Record Dates
Last Update Posted: January 4, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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
ORF15
adeno-associated virus
gene therapy
AAV

Additional relevant MeSH terms:
Retinitis
Retinitis Pigmentosa
Cone-Rod Dystrophies
Retinal Diseases
Eye Diseases
Eye Diseases, Hereditary
Retinal Dystrophies
Retinal Degeneration
Genetic Diseases, Inborn