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History of Changes for Study: NCT05748873
Promising ROd-cone DYstrophy Gene therapY (PRODYGY)
Latest version (submitted May 31, 2023) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 February 17, 2023 None (earliest Version on record)
2 April 12, 2023 Recruitment Status, Contacts/Locations, Study Status, Eligibility and Oversight
3 May 31, 2023 Study Status and Contacts/Locations
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Study NCT05748873
Submitted Date:  February 17, 2023 (v1)

Open or close this module Study Identification
Unique Protocol ID: SPVN06-CLIN-01
Brief Title: Promising ROd-cone DYstrophy Gene therapY (PRODYGY)
Official Title: A Phase I/II Study to Assess the Safety and Tolerability of a Single Subretinal Administration of SPVN06 Gene Therapy in Subjects With Rod-Cone Dystrophy (RCD) Due to a Mutation in the RHO, PDE6A, or PDE6B Gene
Secondary IDs:
Open or close this module Study Status
Record Verification: February 2023
Overall Status: Not yet recruiting
Study Start: February 2023
Primary Completion: March 2025 [Anticipated]
Study Completion: March 2029 [Anticipated]
First Submitted: February 7, 2023
First Submitted that
Met QC Criteria:
February 17, 2023
First Posted: March 1, 2023 [Actual]
Last Update Submitted that
Met QC Criteria:
February 17, 2023
Last Update Posted: March 1, 2023 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: SparingVision
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary: This is a two-step, multicenter, Phase I/II study including an open-label dose-escalation phase (Step 1) and a three-arm controlled double-masked randomized extension phase (Step 2), in subjects with advanced RCD due to a mutation in the RHO, PDE6A, or PDE6B gene.
Detailed Description:
Open or close this module Conditions
Conditions: Retinitis Pigmentosa
Keywords: RHO
PDE6A
PDE6B
Pathogenic Mutation
Retinal Disease
Eye Disease
Rod-Cone Dystrophy
Gene Therapy
Retinal Dystrophies
Retinal Degeneration
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1/Phase 2
Interventional Study Model: Parallel Assignment
Phase I/II study including an open-label dose-escalation phase (Step 1) and a three-arm, controlled, double-masked, randomized extension phase (Step 2)
Number of Arms: 6
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation: Randomized
Enrollment: 33 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Step 1 : SPVN06 dose 1
Participants will receive a single subretinal injection of SPVN06 Dose 1 on Day 0.
Drug: SPVN06
AAV-RdCVF-RdCVFL
Experimental: Step 1 : SPVN06 dose 2
Participants will receive a single subretinal injection of SPVN06 Dose 2 on Day 0
Drug: SPVN06
AAV-RdCVF-RdCVFL
Experimental: Step 1 : SPVN06 dose 3
Participants will receive a single subretinal injection of SPVN06 Dose 3 on Day 0
Drug: SPVN06
AAV-RdCVF-RdCVFL
Experimental: Step 2 : SPVN06 Dose Recommended 1
Participants will receive a single subretinal injection of SPVN06 recommended dose 1 on Day 0
Drug: SPVN06
AAV-RdCVF-RdCVFL
Experimental: Step 2 : SPVN06 Dose Recommended 2
Participants will receive a single subretinal injection of SPVN06 recommended dose 2 on Day 0
Drug: SPVN06
AAV-RdCVF-RdCVFL
No Intervention: Step 2 : Control group
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Evaluation of the safety and tolerability of a single injection of SPVN06 in subjects with advanced RCD due to a mutation in the RHO, PDE6A, or PDE6B gene, 12 months after administration of gene therapy.
[ Time Frame: Baseline to 12 months after administration of gene therapy ]

Incidence and severity of systemic and ocular AEs and SAEs
Secondary Outcome Measures:
1. Evaluation of the long-term safety and tolerability of a single injection of SPVN06 in subjects with advanced RCD due to a mutation in the RHO, PDE6A, or PDE6B gene, up to 5 years after treatment administration.
[ Time Frame: up to 5 years after treatment ]

Incidence and severity of systemic and ocular AEs and SAEs
2. Evaluation of viral shedding and bio-dissemination up to 6 months after treatment administration.
[ Time Frame: up to 6 months after treatment ]

Quantification of viral DNA copies in tears (viral shedding) and in blood (bio-dissemination)
3. Evaluation of the immune response against the viral vector of SPVN06 up to 5 years after treatment administration.
[ Time Frame: up to 5 years after treatment ]

Titration of total antibodies against the viral capsid
4. Evaluation of preliminary efficacy as assessed by visual acuity
[ Time Frame: up to 5 years after treatment ]

BCVA change from baseline (EDTRS chart)
5. Evaluation of preliminary efficacy as assessed by optical coherence tomography
[ Time Frame: up to 5 years after treatment ]

Anatomical change from baseline (SD-OCT)
6. Evaluation of preliminary efficacy as assessed by color vision
[ Time Frame: up to 5 years after treatment ]

Change from baseline of parameters collected by Cambridge and Lanthony tests
7. Evaluation of preliminary efficacy as assessed by visual field
[ Time Frame: up to 5 years after treatment ]

Change from baseline of static perimetry, kinetic perimetry and microperimetry
8. Evaluation of preliminary efficacy as assessed by retinal sensitivity
[ Time Frame: up to 5 years after treatment ]

Change from baseline of parameters collected by full-field electroretinography
9. Evaluation of preliminary efficacy as assessed by retinal sensitivity
[ Time Frame: up to 5 years after treatment ]

Change from baseline of parameters collected by FST
10. Evaluation of preliminary efficacy as assessed by FAF
[ Time Frame: up to 5 years after treatment ]

Change from baseline of parameters collected by fundus autofluorescence
11. Evaluation of preliminary efficacy as assessed by adaptive optics imaging
[ Time Frame: up to 5 years after treatment ]

Change from baseline of parameters collected by RTX1 and AOSLO
12. Evaluation of preliminary efficacy as assessed by quality of life
[ Time Frame: up to 5 years after treatment ]

Change from baseline of parameters collected by VFQ-25
13. Evaluation of preliminary efficacy as assessed by quality of life
[ Time Frame: up to 5 years after treatment ]

Change from baseline of parameters collected by ViSIO-PRO
Other Outcome Measures:
1. Exploratory objective
[ Time Frame: up to 5 years after treatment ]

Collect and store urine and blood (in addition to the body fluids used for the assessment of viral shedding and bio-dissemination) for further exploration of biomarkers of medical interest not already identified at time of protocol submission.
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

Subjects will be eligible to participate in this study only if all the following criteria apply:

  1. Able to give signed informed consent and comply with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
  2. Age ≥18 years at the time of ICF signature.
  3. Subjects of either gender previously diagnosed with advanced RCD due to biallelic mutations in the rod cGMP phosphodiesterase 6 beta (PDE6B) or rod cGMP phosphodiesterase alpha (PDE6A) genes, or due to a monoallelic dominant mutation in the rhodopsin (RHO) gene. The genotyping results must be documented before the initiation of the Screening Visit. Subjects should be retested by the investigator if their genotyping tests were not performed within the 3 previous years, or if they were not performed by an accredited laboratory. In this case, the screening period can be prolonged for 2 additional weeks to allow time to generate genotyping results.
  4. Advanced stage is defined as a stage of the natural history of the disease where both distance visual acuity and visual field are affected in both eyes. Substages within the advanced stage are defined as follows (monocular measurements, horizontal axis of isopter III4e for the visual field):

    Severe stage is defined by both a BCVA below or equal to 20/200 and above or equal to 20/400, and a visual field below or equal to 20 degrees (subjects of Cohorts 1 to 3)

    Intermediate stage is defined by both a BCVA below or equal to 20/40 and above 20/200, and a visual field below or equal to 20 degrees (subjects of Cohort 4)

  5. Regardless of the severity of the disease, the difference in visual acuity between the two eyes of a given subject should be equal to or below 0.3 logarithm of the minimal angle (LogMAR) (≤ 3 ETDRS lines).
  6. Clinical diagnosis of RCD based on past medical and family history, mid-peripheral visual field dysfunction, photopsia, night blindness (nyctalopia), and funduscopic appearance (including but not restricted to bone spicule pigmentation, attenuation of the retinal vessels, and waxy pallor of the optic nerve).
  7. Diagnosis of RCD is confirmed on prior full-field ERG (any previously performed ERG is acceptable).
  8. Documented preservation of cone inner and outer segments considered good enough by the investigator for the subject to be included in the study.
  9. Negative serum pregnancy test for women of childbearing potential (please refer to Schedule of Assessments for details).
  10. Women and men of reproductive potential must agree to use adequate contraception when sexually active. This applies to the time period between ICF signature and 12 months after SPVN06 subretinal injection (SRI). The definition of adequate contraception follows CTFG recommendations. Subjects must agree to utilize 2 reliable and acceptable methods of contraception simultaneously. Acceptable methods of contraception include, but are not limited to:

    Barrier contraception (male or WOCBP) with or without a spermicidal agent Diaphragm or cervical cap with spermicide (WOCBP) Intrauterine device (WOCBP) Hormone-based contraception (WOCBP)

  11. Subjects must be affiliated to a health security system, if they are included in a clinical site based in France (per law).
  12. No out-of-range values for clinical laboratory tests, however, if outside, must be considered as non-clinically relevant by the investigator using a multidisciplinary approach and compatible with a participation in the clinical study.
  13. 12-lead electrocardiogram within normal limits, however, when outside, must be documented by the investigator using a multidisciplinary approach as not clinically relevant and compatible with a participation in the clinical study
  14. Physical examination without any clinical findings of clinical relevance (per medical/anesthesia staff judgement) that could compromise participation in the clinical study or could affect the collection and/or evaluation of the study parameters. The findings of clinical relevance considered as contraindications to SPVN06 treatment include, but are not limited to, pulmonary pathology such as COPD, asthma, cardiac conditions such as congestive heart failure or valve disease, renal issues such as renal insufficiency and endocrine issues such as diabetes.

Exclusion Criteria:

Subjects are not eligible to participate in this study if any of the following criteria apply:

  1. Subjects with prior administration of any gene therapy or any previous treatment with stem cell therapy for ocular or non-ocular disease.
  2. Subjects participating in another clinical trial and receiving an investigational medicinal product (IMP) within 5 half-lives or 90 days prior to the injection of SPVN06
  3. Subjects with RCD due to any mutation in genes other than those listed in the inclusion criteria.
  4. Subjects with systemic disease or other pathology not related to their diagnosis of RCD, and whose symptoms or associated treatments may affect vision, for example cancers or pathology of the central nervous system.
  5. Subjects with narrow irido-corneal angles or any other medical situation contraindicating pupillary dilation.
  6. Subjects known to be allergic to any of the delivery vehicle constituents or to any other drugs planned to be used during the clinical study.
  7. Subjects with known allergies to corticosteroids, or who will be unable to tolerate the corticosteroid regimen as described in Section 9.2.1.
  8. Subjects with systemic disease or other medical or psychiatric conditions that preclude safe participation in the study.
  9. Subjects receiving immunosuppressive therapies, other than the immune modulating regimen described in this protocol, or any other therapy known to influence the immune system including but not limited to steroid implants, cytostatics, interferons, tumor necrosis factor (TNF) binding proteins, drugs acting on immunophilins, or antibodies with known impact on the immune system.
  10. Subjects of reproductive potential unwilling to use effective contraception starting right after ICF signature and for 12 months after SPVN06 SRI.
  11. Subjects who are pregnant or breastfeeding.
  12. Subjects who are unwilling or unable (based on the investigator's judgment) to comply with the study protocol.
  13. Subjects with any condition that would not allow them to complete follow-up examinations during the study and, in the opinion of the investigator, would make them unsuitable for the study.
  14. Subjects positive for human immunodeficiency virus (HIV) or any other systemic immunocompromising disease.
  15. Subjects who have undergone, within 6 months before inclusion, any significant ocular surgery (per investigator's judgment) that could interfere with the evaluation of SPVN06 study objectives.
  16. Presence of eye disorders that could interfere with the assessment of visual acuity and/or any other ocular assessments, including SD-OCT, during the study.
  17. Presence of any systemic or ocular diseases, other than non-syndromic retinitis pigmentosa (RP), that can cause vision loss.
  18. Prior vitrectomy or vitreomacular surgery.
  19. Presence of vitreomacular adhesion or traction, epiretinal membrane macular pucker or macular hole, evident by ophthalmoscopy and/or SD-OCT examinations and assessed by the investigator to significantly affect central vision.
  20. Current evidence of retinal detachment assessed by the investigator to significantly affect central vision.
  21. Active ocular inflammation or recurrent history of idiopathic or autoimmune-associated uveitis.
  22. Subjects with presence of any suspected or active ocular or periocular infection (conjunctivitis, keratitis, scleritis, endophthalmitis).
  23. Subjects with history of glaucoma.
  24. Subjects with uncontrolled intraocular pressure (IOP).
  25. Subjects with active cancer or currently receiving any therapy for cancer treatment.
  26. Subjects with any history of ocular malignancy.
  27. Subjects with a clinically significant cardiac disease on routine clinical examination (history, physical examination), or known congestive heart failure, myocardial infarction, clinically significant valvular heart disease, clinically significant cardiac rhythm or conduction abnormalities.
  28. Subjects with unstable/uncontrolled hypertension, defined by national recommendations.
  29. Subjects with pulmonary dysfunction or severe obstructive pulmonary disease.
  30. Subjects with active tuberculosis.
  31. Subjects with liver or renal insufficiency.
  32. Subjects with unstable endocrine disease, including unstable diabetes or thyroid disease.
  33. Subjects with active Hepatitis B or Hepatitis C.
  34. Subjects with clinically active infection of herpetic diseases, including herpes simplex virus, varicella zoster virus (VZV), cytomegalovirus (CMV) or EBV.
  35. Subjects with known history of ocular infection with herpes simplex virus.
  36. Subjects with active (extraocular) infection (requiring or not the prolonged or chronic use of antimicrobial agents).
  37. Immunocompromised subjects with previous solid organ or bone marrow transplant. 38. Subjects who receive a live vaccine less than 4 weeks prior to the SPVN06 injection

39. Subjects who were infected by COVID-19 less than 2 weeks prior to SPVN06 injection.

40. Subjects who have recently received (less than 4 weeks) or plan to receive a COVID-19 vaccination.

41. Incapacitated subjects, as defined by national laws.

Open or close this module Contacts/Locations
Central Contact Person: SparingVision
Telephone: +33143462060
Email: info@sparingvision.com
Central Contact Backup: Medical Director
Locations: United States, Pennsylvania
UPMC Eye Center
Pittsburgh, Pennsylvania, United States, 15213
Contact:Contact: Study Coordinator 412-647-5756
France
CHNO XV-XX Paris - CIC 1423
Paris, France, 75012
Contact:Contact: Study Coordinator
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations:
Links:
Available IPD/Information:

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