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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 : April 24, 2019
Sponsor:
Information provided by (Responsible Party):
GenSight Biologics

Tracking Information
First Submitted Date  ICMJE October 11, 2017
First Posted Date  ICMJE October 31, 2017
Last Update Posted Date April 24, 2019
Actual Study Start Date  ICMJE September 26, 2018
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 25, 2017)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03326336 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 25, 2017)
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dose-escalation Study to Evaluate the Safety and Tolerability of GS030 in Subjects With Retinitis Pigmentosa
Official Title  ICMJE A Phase 1/2a, Open-Label, Non-Randomized, Dose-Escalation Study to Evaluate the Safety and Tolerability of GS030 in Subjects With Retinitis Pigmentosa
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
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE 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
Condition  ICMJE Non-syndromic Retinitis Pigmentosa
Intervention  ICMJE 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)
Study Arms  ICMJE 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.
Intervention: Combination Product: Gene therapy: GS030-DP AND Medical device: GS030-MD
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 25, 2017)
18
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2025
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Barrett Katz, MD +1 646 831 3799 bkatz@GENSIGHT-BIOLOGICS.COM
Contact: Magali Taeil, MD +33 (0)7 62 89 12 52 mtaeil@gensight-biologics.com
Listed Location Countries  ICMJE France,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03326336
Other Study ID Numbers  ICMJE GS030_CLIN_001
2017-002204-27 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party GenSight Biologics
Study Sponsor  ICMJE GenSight Biologics
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account GenSight Biologics
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP