Dose-escalation Study to Evaluate the Safety and Tolerability of GS030 in Subjects With Retinitis Pigmentosa (PIONEER)

A Phase 1/2a, Open-Label, Non-Randomized, Dose-Escalation Study to Evaluate the Safety and Tolerability of GS030 in Subjects With Retinitis Pigmentosa

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

Study Overview

• Status: Active, not recruiting
• Conditions: Non-syndromic Retinitis Pigmentosa
• Intervention / Treatment: Combination product: Gene therapy: GS030-DP AND Medical device: GS030-MD

Detailed Description

Study GS030_CLIN_001 is a multicenter, Phase 1/2a, open-label, non-randomized, dose-escalation, safety and tolerability study of GS030-DP in association with GS030-MD in subjects with non-syndromic RP that is confirmed by full-field ERG. The study design includes a dose escalation of the vector encoding the ChR-tdT. This first-in-human study design evaluates the safety and tolerability of GS030, the associated GS030-MD and GS030-DP, which is the treatment to be developed and considered for marketing.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Paris, France, 75012
    • Centre Hospitalier National d'Ophtalmologie (CHNP) des Quinze-Vingts
• United Kingdom
  • London, United Kingdom
    • Moorfields Eye Hospital NHS Foundation Trust, 162 City Road
• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Eye Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion 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.

Exclusion 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Cohort; 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.

Combination product: Gene therapy: GS030-DP AND Medical device: GS030-MD; 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Week 52/Year 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Week 52/Year 1
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).	Week 52/Year 1
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	Week 52/Year 1
Evaluate the treatment effect of GS030 as assessed by mobility (door task).	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).	Week 52/Year 1
Evaluate the treatment effect of GS030 as assessed by mobility (line task).	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).	Week 52/Year 1
Evaluate the treatment effect of GS030 as assessed by QoL (VFQ25)	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.	Week 52/Year 1
Evaluate the treatment effect of GS030 as assessed by QoL (SF36)	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).	Week 52/Year 1

Collaborators and Investigators

• Sponsor: GenSight Biologics
• Investigators: Study Director: GenSight Biologics, GenSight Biologics

Publications and helpful links

Helpful Links

• Website of GenSight Biologics

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2018
• Primary Completion (Estimated): October 26, 2027
• Study Completion (Estimated): October 26, 2027

Study Registration Dates

• First Submitted: October 11, 2017
• First Submitted That Met QC Criteria: October 25, 2017
• First Posted (Actual): October 31, 2017

Study Record Updates

• Last Update Posted (Actual): March 2, 2026
• Last Update Submitted That Met QC Criteria: February 27, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Gene Therapy; Eye Diseases; Hereditary Eye Diseases; Intravitreal Injections; Retinitis Pigmentosa; Medical device; Retinal degeneration; Inherited retinal diseases; Rod & cone dystrophies; Optogenetic; AAV Vectors; Visual Interface
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Retinal Diseases; Retinal Dystrophies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cone-Rod Dystrophies; Eye Diseases; Retinitis Pigmentosa; Retinal Degeneration; Eye Diseases, Hereditary
• Other Study ID Numbers: GS030_CLIN_001; 2017-002204-27 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes