A Clinical Trial of Retinal Gene Therapy for X-linked Retinitis Pigmentosa using AAV8

• Register: EUCTR
• Last refreshed on: 3 November 2020
• Main ID: EUCTR2016-003852-60-GB
• Date of registration: 09/11/2016
• Prospective Registration: Yes
• Primary sponsor: NightstaRx Limited
• Public title: A Clinical Trial of Retinal Gene Therapy for X-linked Retinitis Pigmentosa using AAV8
• Scientific title: A Dose Escalation (Phase 1), and Dose Expansion (Phase 2/3) Clinical Trial of Retinal Gene Therapy for X-linked Retinitis Pigmentosa Using an Adeno-Associated Viral Vector (AAV8) Encoding Retinitis Pigmentosa GTPase Regulator (RPGR) - XIRIUS Study
• Date of first enrolment: 09/01/2017
• Target sample size: 63
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-003852-60
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: yes; Other trial design description: Double-Masked; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: yes; Other specify the comparator: Untreated control; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

United Kingdom, United States

Contacts

• Name: Clinical Operations Department
• Affiliation: NightstaRx Limited

• Name: Clinical Operations Department
• Affiliation: NightstaRx Limited

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects are eligible for study participation if they meet all of the following inclusion criteria:
Part I
1. Subject is willing and able to give informed consent for participation in the study
2. Are male, =18 years of age, and able to comply and adequately perform all study assessments
3. Have a genetically confirmed diagnosis of XLRP (with RPGR mutation)
Part II
1. Subject / parent (if applicable) is willing and able to provide informed consent for participation in the study
2. Are male, =10 years of age, and able to comply and adequately perform all study assessments
3. Documentation of a pathogenic mutation in the RPGR gene
Are the trial subjects under 18? yes
Number of subjects for this age range: 20
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 43
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Parts 1 and II:
Subjects are not eligible for study participation if they meet any of the
following exclusion criteria.
1. Have a history of amblyopia in either eye
2. Are unwilling to use barrier contraception methods (if applicable), or abstain from sexual intercourse, for a period of 3 months following treatment with AAV8-RPGR
3. Have participated in another research study involving an investigational product in the past 12 weeks or received a gene/cell-based therapy at any time previously


Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Eye Diseases [C11]

X-Linked retinitis pigmentosa (XLRP)
MedDRA version: 20.0 Level: PT Classification code 10038914 Term: Retinitis pigmentosa System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Product Name: AAV8-RPGR
Product Code: AAV8-RPGR
Pharmaceutical Form: Suspension for injection
CAS Number: 2246424-95-1
Current Sponsor code: AAV8-RPGR
Other descriptive name: AAV8-RPGR
Concentration type: equal
Concentration number: 5.0 x 10E11 gp/ml-

Primary Outcome(s)

Main Objective: To assess the safety, tolerability and efficacy of a single sub-retinal injection of AAV8-RPGR in subjects with XLRP

Secondary Objective: Not applicable

Timepoint(s) of evaluation of this end point: Part I: Incidence of dose-limiting toxicities (DLTs), and treatment-emergent adverse events (TEAEs) over a 24-month period.
Part II:
Microperimetry will be assessed at regular intervals throughout the study.

Primary end point(s): Part I:
The primary safety endpoints are the incidence of dose-limiting toxicities (DLTs), and treatment-emergent adverse events (TEAEs) over a 24-month period.

Part II:
The primary efficacy endpoint is improvement from Baseline in microperimetry.

Secondary Outcome(s)

Secondary end point(s): Part I:
Secondary and Exploratory Endpoints:
•Change from baseline in microperimetry at regular intervals throughout the study
•Change from baseline in best-corrected visual acuity (BCVA) at regular intervals throughout the study

Part II:
Secondary Endpoints:
• The safety endpoint is incidence of TEAEs over a 12-month period.
• Change from baseline in microperimetry at regular intervals throughout the study.
• Change from baseline in best-corrected visual acuity (BCVA) at regular intervals throughout the year.
• Other secondary and exploratory ophthalmology endpoints are assessed at regular intervals throughout the study.

Timepoint(s) of evaluation of this end point: Part I - Secondary and Exploratory Endpoints:
•Microperimetry at regular intervals throughout the study
•BCVA at regular intervals throughout the study
•Other secondary and exploratory ophthalmology endpoints are assessed at regular intervals throughout the study.

Part II - Secondary and Exploratory Endpoints:
•Microperimetry at regular intervals throughout the study
•BCVA at regular intervals throughout the study
•Other secondary and exploratory ophthalmology endpoints are assessed at regular intervals throughout the study.

Secondary ID(s)

NSR-RPGR-01

Source(s) of Monetary Support

NightstaRx Limited

Ethics review

Status: Approved
Approval date: 22/12/2016
Contact: