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

• ClinicalTrials.gov Identifier: NCT03326336
• Recruitment Status: Recruiting
• First Posted: October 31, 2017
• Last Update Posted: July 26, 2022
• Sponsor: GenSight Biologics
• Information provided by (Responsible Party): GenSight Biologics

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

Condition or disease	Intervention/treatment	Phase
Non-syndromic Retinitis Pigmentosa	Combination Product: Gene therapy: GS030-DP AND Medical device: GS030-MD	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Intervention 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)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: September 26, 2018
• Estimated Primary Completion Date: December 2022
• Estimated Study Completion Date: December 2025

Arms and Interventions

Arm

Intervention/treatment

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)

Outcome Measures

Primary Outcome Measures :

1. 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 [ Time Frame: Week 52/Year 1 ]
   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 :

1. Evaluate the treatment effect of GS030 as assessed by visual acuity [ Time Frame: Week 52/Year 1 ]
   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).
2. Evaluate the treatment effect of GS030 as assessed by visual function [ Time Frame: Week 52/Year 1 ]
   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).
3. Evaluate the treatment effect of GS030 as assessed by mobility. [ Time Frame: Week 52/Year 1 ]
   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).
4. Evaluate the treatment effect of GS030 as assessed by mobility. [ Time Frame: Week 52/Year 1 ]
   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).
5. Evaluate the treatment effect of GS030 as assessed by QoL [ Time Frame: Week 52/Year 1 ]
   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.
6. Evaluate the treatment effect of GS030 as assessed by QoL [ Time Frame: Week 52/Year 1 ]
   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).
7. Evaluate immune response to recombinant adeno associated viral vector, derived from serotype 2 (rAAV2.7m8) and ChR tdT protein. [ Time Frame: Week 52/Year 1 ]
   Immune response to rAAV2.7m8 and ChR-tdT protein from baseline to week 52

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Magali Taiel, MD; +33 (0)7 62 89 12 52; mtaiel@gensight-biologics.com

Contact: Michel Roux, MD; +33 (0)1 76 21 72 36; mroux@gensight-biologics.com

Locations

United States, Pennsylvania

UPMC Eye Center; Recruiting

Pittsburgh, Pennsylvania, United States, 15213

Contact: Joseph Martel, MD 412-647-3434

Principal Investigator: Joseph Martel, MD

France

Centre Hospitalier National d'Ophtalmologie (CHNP) des Quinze-Vingts; Recruiting

Paris, France, 75012

Contact: Elise BOULANGER-SCEMAMA, MD +33 665895460 eboulanger@for.paris

Principal Investigator: Elise BOULANGER-SCEMAMA, MD

United Kingdom

Moorfields Eye Hospital NHS Foundation Trust, 162 City Road; Recruiting

London, United Kingdom

Contact: Simona ESPOSTI, Dr

Contact s.esposti@nhs.net

Principal Investigator: Simona ESPOSTI, MD

Sponsors and Collaborators

GenSight Biologics

More Information

Additional Information:

Related Info 

• Responsible Party: GenSight Biologics
• ClinicalTrials.gov Identifier: NCT03326336
• Other Study ID Numbers: GS030_CLIN_001; 2017-002204-27 ( EudraCT Number )
• First Posted: October 31, 2017
• Last Update Posted: July 26, 2022
• Last Verified: July 2022

• 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

Keywords provided by GenSight Biologics:

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

Additional relevant MeSH terms:

Retinitis; Retinitis Pigmentosa; Retinal Diseases; Eye Diseases; Eye Diseases, Hereditary; Retinal Dystrophies; Retinal Degeneration; Genetic Diseases, Inborn