Clinical Trials/NCT05748873

NCT05748873

Recruiting

Phase 1

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

SparingVision6 sites in 2 countries33 target enrollmentApril 12, 2023

ConditionsRetinitis Pigmentosa

InterventionsSPVN06

DrugsSPVN06

Overview

Phase: Phase 1
Intervention: SPVN06
Conditions: Retinitis Pigmentosa
Sponsor: SparingVision
Enrollment: 33
Locations: 6
Primary Endpoint: 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.
Status: Recruiting
Last Updated: 7 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

April 12, 2023

End Date

September 1, 2030

Last Updated

7 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

SparingVision

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Subjects will be eligible to participate in this study only if all the following criteria apply:
•Able to give signed informed consent and comply with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.
•Age ≥18 years at the time of ICF signature.
•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.
•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 Cohorts 4 to 6)
•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).
•Clinical diagnosis of RCD based on past medical and family history, mid-peripheral visual field dysfunction, photopsia, night blindness (nyctalopia), and fundoscopic appearance (including but not restricted to bone spicule pigmentation, attenuation of the retinal vessels, and waxy pallor of the optic nerve).
•Diagnosis of RCD is confirmed on prior full-field ERG (any previously performed ERG is acceptable).

Exclusion Criteria

•Subjects are not eligible to participate in this study if any of the following criteria apply:
•Subjects with prior administration of any gene therapy or any previous treatment with stem cell therapy for ocular or non-ocular disease.
•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 SPVN
•Subjects with RCD due to any mutation in genes other than those listed in the inclusion criteria.
•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.
•Subjects with narrow irido-corneal angles or any other medical situation contraindicating pupillary dilation.
•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.
•Subjects with known allergies to corticosteroids, or who will be unable to tolerate the corticosteroid regimen as described in the protocol
•Subjects with systemic disease or other medical or psychiatric conditions that preclude safe participation in the study.
•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.

Arms & Interventions

Step 1 : SPVN06 dose 2

Participants will receive a single subretinal injection of SPVN06 Dose 2 on Day 0

Intervention: SPVN06

Step 1 : SPVN06 dose 1

Participants will receive a single subretinal injection of SPVN06 Dose 1 on Day 0.

Intervention: SPVN06

Step 1 : SPVN06 dose 3

Participants will receive a single subretinal injection of SPVN06 Dose 3 on Day 0

Intervention: SPVN06

Step 2 : SPVN06 Dose Recommended 1

Participants will receive a single subretinal injection of SPVN06 recommended dose 1 on Day 0

Intervention: SPVN06

Step 2 : SPVN06 Dose Recommended 2

Participants will receive a single subretinal injection of SPVN06 recommended dose 2 on Day 0

Intervention: SPVN06

Outcomes

Primary Outcomes

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 Outcomes

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.(up to 5 years after treatment)
Evaluation of preliminary efficacy as assessed by visual acuity(up to 5 years after treatment)
Evaluation of viral shedding and bio-dissemination up to 1 year after treatment administration.(up to 1 year after treatment)
Evaluation of the immune response against the viral vector and the transgene products of SPVN06 up to 5 years after treatment administration.(up to 5 years after treatment)
Evaluation of preliminary efficacy as assessed by optical coherence tomography(up to 5 years after treatment)
Evaluation of preliminary efficacy as assessed by color vision(up to 5 years after treatment)
Evaluation of preliminary efficacy as assessed by visual field(up to 5 years after treatment)
Evaluation of preliminary efficacy as assessed by retinal sensitivity(up to 5 years after treatment)
Evaluation of preliminary efficacy as assessed by FAF(up to 5 years after treatment)
Evaluation of preliminary efficacy as assessed by quality of life(up to 5 years after treatment)