Dose-escalation Study to Evaluate the Safety and Tolerability of GS030 in Subjects With Retinitis Pigmentosa (PIONEER)
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|ClinicalTrials.gov Identifier: NCT03326336|
Recruitment Status : Recruiting
First Posted : October 31, 2017
Last Update Posted : July 26, 2022
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|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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||15 participants|
|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)|
|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|
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)
- 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.
- 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).
- 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).
- 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).
- 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).
- 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.
- 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).
- 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
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|Ages Eligible for Study:||18 Years to 75 Years (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
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 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.
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): NCT03326336
|Contact: Magali Taiel, MD||+33 (0)7 62 89 12 email@example.com|
|Contact: Michel Roux, MD||+33 (0)1 76 21 72 firstname.lastname@example.org|
|United States, Pennsylvania|
|UPMC Eye Center||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15213|
|Contact: Joseph Martel, MD 412-647-3434|
|Principal Investigator: Joseph Martel, MD|
|Centre Hospitalier National d'Ophtalmologie (CHNP) des Quinze-Vingts||Recruiting|
|Paris, France, 75012|
|Contact: Elise BOULANGER-SCEMAMA, MD +33 665895460 email@example.com|
|Principal Investigator: Elise BOULANGER-SCEMAMA, MD|
|Moorfields Eye Hospital NHS Foundation Trust, 162 City Road||Recruiting|
|London, United Kingdom|
|Contact: Simona ESPOSTI, Dr|
|Principal Investigator: Simona ESPOSTI, MD|
|Responsible Party:||GenSight Biologics|
|Other Study ID Numbers:||
2017-002204-27 ( EudraCT Number )
|First Posted:||October 31, 2017 Key Record Dates|
|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|
Hereditary Eye Diseases
Inherited retinal diseases
Rod & cone dystrophies
Eye Diseases, Hereditary
Genetic Diseases, Inborn