Promising ROd-cone DYstrophy Gene therapY

NCT05748873 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: SPVN06-CLIN-01
• Study Type: interventional
• Target: 33
• Locations: 2 countries
• Sites: 6

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.

Conditions

Retinitis Pigmentosa

Keywords

RHO; PDE6A; PDE6B; Pathogenic Mutation; Retinal Disease; Eye Disease; Rod-Cone Dystrophy; Gene Therapy; Retinal Dystrophies; Retinal Degeneration

Outcome Measures

Primary Outcomes (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.

  Incidence and severity of systemic and ocular AEs and SAEs

  Baseline to 12 months after administration of gene therapy

Secondary Outcomes (12)

• 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 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 visual acuity

  up to 5 years after treatment

• Evaluation of preliminary efficacy as assessed by optical coherence tomography

  up to 5 years after treatment

Other Outcomes (2)

• Exploratory objective - Exploration of biomarkers

  up to 5 years after treatment

• Exploratory objective - Photoreceptor mosaic imaging

  up to 5 years after treatment

Study Arms (6)

Step 1 : SPVN06 dose 1

EXPERIMENTAL

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

Drug: SPVN06

Step 1 : SPVN06 dose 2

EXPERIMENTAL

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

Drug: SPVN06

Step 1 : SPVN06 dose 3

EXPERIMENTAL

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

Drug: SPVN06

Step 2 : SPVN06 Dose Recommended 1

EXPERIMENTAL

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

Drug: SPVN06

Step 2 : SPVN06 Dose Recommended 2

EXPERIMENTAL

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

Drug: SPVN06

Step 2 : Control group

NO INTERVENTION

Interventions

SPVN06 DRUG

AAV-RdCVF-RdCVFL

Step 1 : SPVN06 dose 1; Step 1 : SPVN06 dose 2; Step 1 : SPVN06 dose 3; Step 2 : SPVN06 Dose Recommended 1; Step 2 : SPVN06 Dose Recommended 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 7 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 20/800, 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)
• For subjects with severe advanced RCD enrolled in Step 1 only, 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), with a tolerance margin of 3 ETDRS letters.
• 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).
• Documented preservation of cone inner and outer segments considered good enough by the investigator for the subject to be included in the study.
• Negative serum pregnancy test for women of childbearing potential (please refer to Schedule of Assessments for details).
• Women of childbearing potential (WOCBP) and men and/or their partner(s) of childbearing potential must agree to use a highly effective contraceptive method. This applies to the time period between ICF signature and 12 months after SPVN06 subretinal injection SRI (i.e., no longer applicable to subjects of Cohort 4 after randomization). The definition of highly effective contraceptive methods follows CTFG recommendations. Highly effective contraceptive methods are limited to:
• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
• Oral

You may not qualify if:

• 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 SPVN06.
• 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.
• Subjects of reproductive potential unwilling to use effective contraception starting right after ICF signature and for 12 months after SPVN06 SRI (i.e., no longer applicable to subjects of Cohort 4 after randomization).
• Subjects who are pregnant or breastfeeding.
• Subjects who are unwilling or unable (based on the investigator's judgment) to comply with the study protocol.
• 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.
• Subjects positive for human immunodeficiency virus (HIV) or any other systemic immunocompromising disease.
• 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.

Sponsors & Collaborators

• SparingVision: lead

Study Sites (6)

Bascom Palmer Eye Institute/University of Miami

Miami, Florida, 33136, United States

RECRUITING

Mass Eye and Ear

Boston, Massachusetts, 02114, United States

RECRUITING

Casey Eye Institute

Portland, Oregon, 97239, United States

RECRUITING

UPMC Eye Center

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

Retina Foundation of the Southwest

Dallas, Texas, 75231, United States

RECRUITING

CHNO XV-XX Paris - CIC 1423

Paris, 75012, France

RECRUITING

Related Publications (1)

• Marie M, Churet L, Gautron AS, Farjo R, Mizuyoshi K, Stevenson V, Khabou H, Leveillard T, Sahel JA, Lorget F. Preclinical safety and biodistribution of SPVN06, a novel gene- and mutation-independent gene therapy for rod-cone dystrophies. Gene Ther. 2025 Aug 4. doi: 10.1038/s41434-025-00556-3. Online ahead of print.

  PMID: 40759732 DERIVED

MeSH Terms

Conditions

Retinitis Pigmentosa; Retinal Diseases; Eye Diseases; Cone-Rod Dystrophies; Retinal Dystrophies; Retinal Degeneration

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Central Study Contacts

SparingVision

CONTACT

+33143462060; info@sparingvision.com

Medical Director

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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 Cohorts 5 and 6 of Step 2, subjects and the designated study personnel will be masked to subject's dose assignment. Cohort 4 (untreated group) will be unmasked.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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)

Study Record Dates

• First Submitted: February 7, 2023
• First Posted: March 1, 2023
• Study Start: April 12, 2023
• Primary Completion: September 1, 2025
• Study Completion (Estimated): September 1, 2030
• Last Updated: September 16, 2025

Record last verified: 2024-09

Locations

US (5); FR (1)