Back to resultsDose-escalation Study to Evaluate the Safety and Tolerability of GS030 in Subjects With Retinitis Pigmentosa (PIONEER)
Primary Purpose
Non-syndromic Retinitis Pigmentosa
Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Gene therapy: GS030-DP AND Medical device: GS030-MD
Sponsored by
About this trial
This is an interventional treatment trial for Non-syndromic Retinitis Pigmentosa focused on measuring Eye Diseases, Hereditary Eye Diseases, Retinal degeneration, Inherited retinal diseases, Rod & cone dystrophies, Retinitis Pigmentosa, Gene Therapy, Optogenetic, Intravitreal Injections, AAV Vectors, Medical device, Visual Interface
Eligibility Criteria
Main selection criteria:
- Age ≥18 years to ≤75 years at the time of ICF signature.
Diagnosis of non-syndromic RP defined as:
- Clinical diagnosis of non-syndromic RP based on history, mid-peripheral visual dysfunction, and fundoscopic appearance.
- Diagnosis of non-syndromic RP is confirmed on full-field ERG
Visual acuity:
- Visual acuity in the dose-escalation cohorts of no better LP.
- Visual acuity in the extension cohort of no better than CF pending review of dose-escalation cohort data by the DSMB.
- Relatively preserved ganglion cell layer volume and retinal nerve fiber layer thickness, as measured with spectral domain optical coherence tomography (SD-OCT).
- Interpupillary distance of ≥51 mm and ≤72 mm.
- Refractive error of the study eye between -6 diopters and +6 diopters.
Main non-selection criteria
- Prior receipt of any gene therapy.
- Subjects who have undergone significant ocular surgery (per investigator determination) within 3 months prior to Visit 1.
- Presence of narrow iridocorneal angles contraindicating pupillary dilation.
- Presence of disorders of the ocular media which interfere with visual acuity and other ocular assessments, including SD-OCT, during the study period.
- Presence of any systemic or ocular diseases, or pathologies, other than non-syndromic RP, or their associated therapies, that can cause or have the potential to cause vision loss.
- Prior vitrectomy or vitreomacular surgery.
- Presence of vitreo-macular adhesion or traction, epiretinal membrane, macular pucker and macular hole, evident by ophthalmoscopy and/or by SD-OCT examinations and assessed by the investigator to significantly affect central vision.
- Current evidence of retinal detachment assessed by the investigator to significantly affect central vision.
- Active ocular inflammation or recurrent history of idiopathic or autoimmune associated uveitis.
- Presence of an Active Implantable Medical Device.
- Subjects who have undergone thermal laser procedure to the retina within 3 months of trial entry, or any prior thermal laser procedure to the macular region.
Sites / Locations
- UPMC Eye CenterRecruiting
- Centre Hospitalier National d'Ophtalmologie (CHNP) des Quinze-VingtsRecruiting
- Moorfields Eye Hospital NHS Foundation Trust, 162 City RoadRecruiting
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Cohort
Arm Description
3 dose escalation cohorts (low, medium and high dose) with 3 subjects per cohort followed by an extension cohort at the highest-well tolerated dose with 3 to 9 subjects.
Outcomes
Primary Outcome Measures
The safety and tolerability of escalating doses of GS030-DP administered via a single IVT and repeated light stimulation using GS030-MD in subjects with non-syndromic Retinitis Pigmentosa
Safety and tolerability of GS030 treatment at Week 52/Year 1, by assessments based on local and systemic safety issues, specifically those related to IVT of GS030-DP and the subsequent repeated use of GS030-MD, as assessed by incidence of Adverse Events.
Secondary Outcome Measures
Evaluate the treatment effect of GS030 as assessed by visual acuity
Assessment of the treatment effect with the change from baseline to Week 52 of parameters measured with the Freiburg Visual Acuity & Contrast Test (FrACT) free computer program that uses graphics capabilities and psychometric methods to provide automated, self-paced measurement and the full field threshold stimulus test (FST) measuring the illuminance necessary to stimulate the most sensitive parts of the retina, and thus determines a quantifiable stimulation threshold (before and after gene transfer, with GS030-MD turned ON and turned OFF).
Evaluate the treatment effect of GS030 as assessed by visual function
Assessment of the treatment effect with the change from baseline to Week 52 of parameters measured with Humphrey visual field 10-2 Standardized automated perimetry, square localization test, displaying white square at a random location on a black background and direction of motion test measuring the ability of subjects to determine the direction of an object moving in the visual field (before and after gene transfer, with GS030-MD turned ON and turned OFF).
Evaluate the treatment effect of GS030 as assessed by mobility.
Assessment of the treatment effect with the change from baseline to Week 52 of parameters measured with door task (before and after gene transfer, with GS030-MD turned ON and turned OFF).
Evaluate the treatment effect of GS030 as assessed by mobility.
Assessment of the treatment effect with the change from baseline to Week 52 of parameters measured with line task (before and after gene transfer, with GS030-MD turned ON and turned OFF).
Evaluate the treatment effect of GS030 as assessed by QoL
Assessment of the treatment effect on quality of life changes from baseline to Week 52 with the Visual Functioning Questionnaire-25 (VFQ-25). VFQ25 is a 25-item questionnaire with 47 questions, each question has several responses scored on a scale from 0 to 5, 0 to 6, or 0 to 10. Values are calculated in percentages.
Evaluate the treatment effect of GS030 as assessed by QoL
Assessment of the treatment effect on quality of life changes from baseline to Week 52 with the Short Form Survey 36 Version 2 (SF-36v2). The SF-36v2 is a subject-rated 36-item questionnaire assessing subject health. There are 8 scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0 to 100 scale. A lower score indicates more disability, and a higher score indicates less disability (a score of 0 is equivalent to maximum disability, and a score of 100 is equivalent to no disability).
Evaluate immune response to recombinant adeno associated viral vector, derived from serotype 2 (rAAV2.7m8) and ChR tdT protein.
Immune response to rAAV2.7m8 and ChR-tdT protein from baseline to week 52
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03326336
Brief Title
Dose-escalation Study to Evaluate the Safety and Tolerability of GS030 in Subjects With Retinitis Pigmentosa
Acronym
PIONEER
Official Title
A Phase 1/2a, Open-Label, Non-Randomized, Dose-Escalation Study to Evaluate the Safety and Tolerability of GS030 in Subjects With Retinitis Pigmentosa
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Recruiting
Study Start Date
September 26, 2018 (Actual)
Primary Completion Date
December 2022 (Anticipated)
Study Completion Date
December 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GenSight Biologics
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
Yes
Device Product Not Approved or Cleared by U.S. FDA
Yes
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The objective of this study is to evaluate the safety and tolerability of escalating doses of a gene therapy called GS030-DP (injected study treatment) administered via a single intravitreal injection and repeated light stimulation using a medical device called GS030-MD (stimulating glasses) in subjects with documented diagnosis of non-syndromic Retinitis Pigmentosa
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-syndromic Retinitis Pigmentosa
Keywords
Eye Diseases, Hereditary Eye Diseases, Retinal degeneration, Inherited retinal diseases, Rod & cone dystrophies, Retinitis Pigmentosa, Gene Therapy, Optogenetic, Intravitreal Injections, AAV Vectors, Medical device, Visual Interface
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Model Description
3 dose-escalation cohorts with 3 subjects per each cohort plus 1 extension cohort at the highest well-tolerated dose.
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cohort
Arm Type
Other
Arm Description
3 dose escalation cohorts (low, medium and high dose) with 3 subjects per cohort followed by an extension cohort at the highest-well tolerated dose with 3 to 9 subjects.
Intervention Type
Combination Product
Intervention Name(s)
Gene therapy: GS030-DP AND Medical device: GS030-MD
Intervention Description
GS030-Drug Product (GS030-DP) - Recombinant adeno-associated viral vector, derived from serotype 2 (rAAV2.7m8), containing the optimized channelrhodopsin ChrimsonR-tdTomato gene under the control of the ubiquitous CAG promoter (rAAV2.7m8-CAG-ChrimsonR-tdTomato) GS030-Medical Device (GS030-MD) - Visual Interface Stimulating Glasses (that amplify the external visual stimulus to the optogenetically engineered retina)
Primary Outcome Measure Information:
Title
The safety and tolerability of escalating doses of GS030-DP administered via a single IVT and repeated light stimulation using GS030-MD in subjects with non-syndromic Retinitis Pigmentosa
Description
Safety and tolerability of GS030 treatment at Week 52/Year 1, by assessments based on local and systemic safety issues, specifically those related to IVT of GS030-DP and the subsequent repeated use of GS030-MD, as assessed by incidence of Adverse Events.
Time Frame
Week 52/Year 1
Secondary Outcome Measure Information:
Title
Evaluate the treatment effect of GS030 as assessed by visual acuity
Description
Assessment of the treatment effect with the change from baseline to Week 52 of parameters measured with the Freiburg Visual Acuity & Contrast Test (FrACT) free computer program that uses graphics capabilities and psychometric methods to provide automated, self-paced measurement and the full field threshold stimulus test (FST) measuring the illuminance necessary to stimulate the most sensitive parts of the retina, and thus determines a quantifiable stimulation threshold (before and after gene transfer, with GS030-MD turned ON and turned OFF).
Time Frame
Week 52/Year 1
Title
Evaluate the treatment effect of GS030 as assessed by visual function
Description
Assessment of the treatment effect with the change from baseline to Week 52 of parameters measured with Humphrey visual field 10-2 Standardized automated perimetry, square localization test, displaying white square at a random location on a black background and direction of motion test measuring the ability of subjects to determine the direction of an object moving in the visual field (before and after gene transfer, with GS030-MD turned ON and turned OFF).
Time Frame
Week 52/Year 1
Title
Evaluate the treatment effect of GS030 as assessed by mobility.
Description
Assessment of the treatment effect with the change from baseline to Week 52 of parameters measured with door task (before and after gene transfer, with GS030-MD turned ON and turned OFF).
Time Frame
Week 52/Year 1
Title
Evaluate the treatment effect of GS030 as assessed by mobility.
Description
Assessment of the treatment effect with the change from baseline to Week 52 of parameters measured with line task (before and after gene transfer, with GS030-MD turned ON and turned OFF).
Time Frame
Week 52/Year 1
Title
Evaluate the treatment effect of GS030 as assessed by QoL
Description
Assessment of the treatment effect on quality of life changes from baseline to Week 52 with the Visual Functioning Questionnaire-25 (VFQ-25). VFQ25 is a 25-item questionnaire with 47 questions, each question has several responses scored on a scale from 0 to 5, 0 to 6, or 0 to 10. Values are calculated in percentages.
Time Frame
Week 52/Year 1
Title
Evaluate the treatment effect of GS030 as assessed by QoL
Description
Assessment of the treatment effect on quality of life changes from baseline to Week 52 with the Short Form Survey 36 Version 2 (SF-36v2). The SF-36v2 is a subject-rated 36-item questionnaire assessing subject health. There are 8 scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0 to 100 scale. A lower score indicates more disability, and a higher score indicates less disability (a score of 0 is equivalent to maximum disability, and a score of 100 is equivalent to no disability).
Time Frame
Week 52/Year 1
Title
Evaluate immune response to recombinant adeno associated viral vector, derived from serotype 2 (rAAV2.7m8) and ChR tdT protein.
Description
Immune response to rAAV2.7m8 and ChR-tdT protein from baseline to week 52
Time Frame
Week 52/Year 1
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Main selection criteria:
Age ≥18 years to ≤75 years at the time of ICF signature.
Diagnosis of non-syndromic RP defined as:
Clinical diagnosis of non-syndromic RP based on history, mid-peripheral visual dysfunction, and fundoscopic appearance.
Diagnosis of non-syndromic RP is confirmed on full-field ERG
Visual acuity:
Visual acuity in the dose-escalation cohorts of no better LP.
Visual acuity in the extension cohort of no better than CF pending review of dose-escalation cohort data by the DSMB.
Relatively preserved ganglion cell layer volume and retinal nerve fiber layer thickness, as measured with spectral domain optical coherence tomography (SD-OCT).
Interpupillary distance of ≥51 mm and ≤72 mm.
Refractive error of the study eye between -6 diopters and +6 diopters.
Main non-selection criteria
Prior receipt of any gene therapy.
Subjects who have undergone significant ocular surgery (per investigator determination) within 3 months prior to Visit 1.
Presence of narrow iridocorneal angles contraindicating pupillary dilation.
Presence of disorders of the ocular media which interfere with visual acuity and other ocular assessments, including SD-OCT, during the study period.
Presence of any systemic or ocular diseases, or pathologies, other than non-syndromic RP, or their associated therapies, that can cause or have the potential to cause vision loss.
Prior vitrectomy or vitreomacular surgery.
Presence of vitreo-macular adhesion or traction, epiretinal membrane, macular pucker and macular hole, evident by ophthalmoscopy and/or by SD-OCT examinations and assessed by the investigator to significantly affect central vision.
Current evidence of retinal detachment assessed by the investigator to significantly affect central vision.
Active ocular inflammation or recurrent history of idiopathic or autoimmune associated uveitis.
Presence of an Active Implantable Medical Device.
Subjects who have undergone thermal laser procedure to the retina within 3 months of trial entry, or any prior thermal laser procedure to the macular region.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Magali Taiel, MD
Phone
+33 (0)7 62 89 12 52
Email
mtaiel@gensight-biologics.com
First Name & Middle Initial & Last Name or Official Title & Degree
Michel Roux, MD
Phone
+33 (0)1 76 21 72 36
Email
mroux@gensight-biologics.com
Facility Information:
Facility Name
UPMC Eye Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joseph Martel, MD
Phone
412-647-3434
First Name & Middle Initial & Last Name & Degree
Joseph Martel, MD
Facility Name
Centre Hospitalier National d'Ophtalmologie (CHNP) des Quinze-Vingts
City
Paris
ZIP/Postal Code
75012
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elise BOULANGER-SCEMAMA, MD
Phone
+33 665895460
Email
eboulanger@for.paris
First Name & Middle Initial & Last Name & Degree
Elise BOULANGER-SCEMAMA, MD
Facility Name
Moorfields Eye Hospital NHS Foundation Trust, 162 City Road
City
London
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Simona ESPOSTI, Dr
Email
s.esposti@nhs.net
First Name & Middle Initial & Last Name & Degree
Simona ESPOSTI, MD
12. IPD Sharing Statement
Links:
URL
http://www.gensight-biologics.com/
Description
Related Info
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Dose-escalation Study to Evaluate the Safety and Tolerability of GS030 in Subjects With Retinitis Pigmentosa
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