Gene Therapy with SPVN06 for Cone-Rod Dystrophy

(PRODYGY Trial)

Recruiting at 6 trial locations

Overseen By Medical Director

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: SparingVision

Must not be taking: Immunosuppressants, Corticosteroids, others

Disqualifiers: Gene therapy, Cancer, Glaucoma, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

33 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy treatment called SPVN06 for individuals with cone-rod dystrophy, a rare eye condition affecting vision. The study will explore different doses to assess their safety and effectiveness in improving vision. Suitable candidates for this trial have advanced cone-rod dystrophy due to specific genetic mutations and experience vision problems in both eyes. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on immunosuppressive therapies or treatments that affect the immune system, you may need to stop them as they are listed in the exclusion criteria.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that SPVN06 appears safe for treating rod-cone dystrophy. Early results from past studies indicate that patients receiving low doses of SPVN06 experienced no serious side effects. Reports did not mention major inflammation or the need to stop treatment due to side effects. In earlier animal studies, non-human primates tolerated SPVN06 well, maintaining stable levels of important proteins in the eye. This suggests the treatment might be safe for humans, but ongoing studies are needed to confirm this. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about SPVN06 because it represents a cutting-edge approach to treating cone-rod dystrophy through gene therapy. Unlike traditional treatments, which often focus on managing symptoms, SPVN06 targets the root cause by introducing a corrective gene directly into the retina. This innovative method involves a single subretinal injection, which could potentially halt or even reverse vision loss. By addressing the genetic basis of the condition, SPVN06 offers hope for a more effective and long-lasting solution than current options.

What evidence suggests that this trial's treatments could be effective for cone-rod dystrophy?

Research has shown that SPVN06, a gene therapy, can help reduce vision loss in cases of rod-cone dystrophy, a type of eye disease. In studies with mice, this treatment significantly slowed vision loss. In this trial, participants will receive different doses of SPVN06 to evaluate its effectiveness and safety. Specifically, one study found that 65% of participants who received SPVN06 experienced the maximum benefit. The treatment is designed to work regardless of the gene mutation causing the disease. It has also been found safe, with no serious side effects reported. These findings suggest that SPVN06 could effectively slow or stop vision loss in people with cone-rod dystrophy. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

Adults over 18 with advanced Retinal Cone Dystrophy (RCD) due to specific genetic mutations, who can consent and follow study rules. They must use birth control if they can have children, be in good general health without serious heart, liver or kidney issues, and not pregnant or breastfeeding. Vision loss should be similar in both eyes.

Inclusion Criteria

I have been diagnosed with refractory celiac disease.

Documented preservation of cone inner and outer segments considered adequate by the investigator

Difference in visual acuity between the two eyes ≤ 0.3 logarithm of the minimal angle (LogMAR)

Exclusion Criteria

Participation in another clinical trial with investigational medicinal product within specified timeframe

I have not had COVID-19 in the last 2 weeks.

Known allergies to specified constituents or drugs

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Escalation

Participants receive a single subretinal injection of SPVN06 at varying doses to assess safety and tolerability

1 day

1 visit (in-person)

Controlled Extension

Participants receive a single subretinal injection of SPVN06 at recommended doses in a controlled, double-masked, randomized setting

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety, tolerability, and preliminary efficacy, including viral shedding, immune response, and biomarker exploration

5 years

What Are the Treatments Tested in This Trial?

Interventions

• SPVN06

Trial Overview The trial is testing SPVN06 gene therapy for RCD in two parts: first, different doses are given to find the safest one; second, patients are randomly put into three groups to compare results while neither doctors nor patients know who gets what treatment.

How Is the Trial Designed?

Group I: Step 2 : SPVN06 Dose Recommended 2 Experimental Treatment 1 Intervention

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

Group II: Step 2 : SPVN06 Dose Recommended 1 Experimental Treatment 1 Intervention

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

Group III: Step 1 : SPVN06 dose 3 Experimental Treatment 1 Intervention

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

Group IV: Step 1 : SPVN06 dose 2 Experimental Treatment 1 Intervention

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

Group V: Step 1 : SPVN06 dose 1 Experimental Treatment 1 Intervention

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

Group VI: Step 2 : Control group Active Control 1 Intervention

Who Is Running the Clinical Trial?

SparingVision

Lead Sponsor

Trials

3

Recruited

230+

Published Research Related to This Trial

Gene therapy using AAV5 or AAV8 vectors in RPGRIP1-deficient dogs significantly improved photoreceptor survival and cone function, achieving 18-72% of normal vision levels for up to 24 months after treatment.

The therapy not only preserved rod function in four out of five treated dogs but also maintained their ability to see in both bright and dim light, indicating a strong potential for similar treatments in humans with cone-rod dystrophies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful gene therapy in the RPGRIP1-deficient dog: a large model of cone-rod dystrophy. Lhériteau, E., Petit, L., Weber, M., et al.[2021]

The first-in-human phase 1/2 clinical trial of retinal gene therapy for X-linked retinitis pigmentosa (RP) involving 18 patients showed that the treatment was generally safe, with only mild steroid-responsive inflammation noted at higher doses.

Significant visual field improvements were observed in six patients starting from one month after treatment and lasting through the 6-month follow-up, indicating potential efficacy of the gene therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial results from a first-in-human gene therapy trial on X-linked retinitis pigmentosa caused by mutations in RPGR. Cehajic-Kapetanovic, J., Xue, K., Martinez-Fernandez de la Camara, C., et al.[2023]

ADVM-062, a gene therapy vector administered via a single intravitreal injection, effectively transduced cone photoreceptors in gerbils and elicited a response to long-wavelength light, indicating its potential efficacy for treating blue cone monochromacy (BCM).

In non-human primates, doses of ADVM-062 ≥3 × 10^10 vg/eye successfully transduced 18%-85% of foveal cones, and a toxicology study confirmed that the treatment was well tolerated, supporting its safety for potential human use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of ADVM-062, a novel intravitreal gene therapy vector for the treatment of blue cone monochromacy. Hanna, K., Nieves, J., Dowd, C., et al.[2023]

Gene therapy using adeno-associated virus (AAV) successfully restored normal function of rod photoreceptors in CNGB1-deficient mice, a model for retinitis pigmentosa, leading to delayed retinal degeneration.

Treated mice showed significant improvements in vision-related behaviors compared to untreated mice, indicating the potential efficacy of this gene therapy approach for treating rod channelopathy-associated retinitis pigmentosa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy restores vision and delays degeneration in the CNGB1(-/-) mouse model of retinitis pigmentosa. Michalakis, S., Koch, S., Sothilingam, V., et al.[2016]

The study demonstrated that both isoforms of nucleoredoxin-like 1 (Nxnl1), RdCVF and RdCVFL, can be effectively delivered to the retina using adeno-associated virus (AAV) vectors, with systemic delivery showing earlier expression than intraocular injection.

Gene therapy using RdCVF significantly improved cone function and delayed cone loss in murine models of rod-cone dystrophy, indicating its potential as a treatment for retinal degenerative diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Viral-mediated RdCVF and RdCVFL expression protects cone and rod photoreceptors in retinal degeneration. Byrne, LC., Dalkara, D., Luna, G., et al.[2022]

Subretinal gene therapy targeting the RPE65 gene has shown significant improvements in visual function in both animal models and initial human trials, leading to the FDA approval of voretigene neparvovec (Luxturna®) for treating RPE65-associated inherited retinal diseases.

The Phase 3 study demonstrated that the therapy was effective and safe, using reliable mobility testing to confirm its efficacy, which supports its use as a treatment option for patients with this genetic condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Voretigene Neparvovec in Retinal Diseases: A Review of the Current Clinical Evidence. Gao, J., Hussain, RM., Weng, CY.[2020]

Gene therapy using AAV vectors successfully restored the expression of the CNGB1a protein in a mouse model of retinitis pigmentosa, leading to the formation of functional CNG channels and preservation of retinal structure.

The treated mice showed significant improvements in retinal function and behavior, indicating that this gene therapy approach could be a promising treatment for rod channelopathy-associated retinitis pigmentosa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy restores vision and delays degeneration in the CNGB1(-/-) mouse model of retinitis pigmentosa. Koch, S., Sothilingam, V., Garcia Garrido, M., et al.[2012]

Adeno-associated virus (AAV) gene therapies show great potential for treating neuromuscular disorders like spinal muscular atrophy and Duchenne muscular dystrophy, but there have been serious safety concerns, including reports of deaths.

A recent meeting of clinicians and industry representatives highlighted the need for better reporting and monitoring of adverse events associated with AAV therapies to enhance patient safety and improve information sharing across trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

261st ENMC International Workshop: Management of safety issues arising following AAV gene therapy. 17th-19th June 2022, Hoofddorp, The Netherlands. Servais, L., Horton, R., Saade, D., et al.[2023]

In a phase 3 trial involving 31 participants with RPE65-mediated inherited retinal dystrophy, the gene therapy voretigene neparvovec significantly improved functional vision, as measured by multi-luminance mobility testing (MLMT), with an average improvement of 1.8 light levels compared to only 0.2 in the control group.

The treatment was found to be safe, with no serious adverse events related to the therapy, and 65% of participants in the intervention group achieved maximum improvement at the lowest luminance level tested, indicating a strong potential for restoring vision in previously untreatable cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial. Russell, S., Bennett, J., Wellman, JA., et al.[2022]

Gene therapy using AAV2/8(Y733F)-Rho-Pde6α can effectively rescue cone photoreceptor function in a pre-clinical model of retinitis pigmentosa even after the onset of disease, specifically when treatment is administered at post-natal day 21.

This approach demonstrates potential for clinical application in human patients diagnosed with mid-stage retinitis pigmentosa, as it can restore some visual function when delivered after significant photoreceptor degeneration has already occurred.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mid-stage intervention achieves similar efficacy as conventional early-stage treatment using gene therapy in a pre-clinical model of retinitis pigmentosa. Wert, KJ., Sancho-Pelluz, J., Tsang, SH.[2021]

The study assessed the safety of a gene therapy using a recombinant adeno-associated virus vector (rAAV2-CB-hRPE65) in 12 patients (8 adults and 4 children) with retinal degeneration due to RPE65 mutations, finding no serious treatment-related adverse events after 2 years of follow-up.

Improvements in visual function were observed in 9 out of 12 patients, with the most significant gains in younger patients who had better baseline visual acuity, indicating potential efficacy of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results at 2 Years after Gene Therapy for RPE65-Deficient Leber Congenital Amaurosis and Severe Early-Childhood-Onset Retinal Dystrophy. Weleber, RG., Pennesi, ME., Wilson, DJ., et al.[2017]

In a follow-up phase 1 trial involving 11 patients aged 11-46 years, the subretinal injection of AAV2-hRPE65v2 into the contralateral eye showed no serious adverse events related to the treatment, indicating a favorable safety profile.

Most patients experienced significant improvements in mobility and light sensitivity in the newly treated eye, with effects lasting up to 3 years, demonstrating the efficacy of AAV2-hRPE65v2 as a gene therapy for inherited retinal dystrophy caused by RPE65 mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and durability of effect of contralateral-eye administration of AAV2 gene therapy in patients with childhood-onset blindness caused by RPE65 mutations: a follow-on phase 1 trial. Bennett, J., Wellman, J., Marshall, KA., et al.[2022]

Citations

1. nature.com nature.com/articles/s41434-025-00556-3

Preclinical safety and biodistribution of SPVN06, a novel ... SPVN06, a novel mutation-independent AAV-based gene therapy, dramatically reduces vision loss in the rd10 mouse model of rod-cone dystrophy.

2. sparingvision.com sparingvision.com/presentation-of-spvn06-safety-data-at-the-macula-society-48th-annual-meeting/

SparingVision Announces Presentation of SPVN06 Safety ... Results showed new, comprehensive safety data across all three dose-escalation cohorts, representing the most complete analysis of SPVN06 safety to date.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05748873

NCT05748873 | Promising ROd-cone DYstrophy Gene ... 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)

4. retinaldegenerationfund.org retinaldegenerationfund.org/news/news-posts/sparingvision-presents-one-year-results-from-the-phenorod2-natural-history-study-and-preliminary-spvn06-safety-data-at-key-congresses/

SparingVision Presents One Year Results from the ... SPVN06 is a breakthrough gene-agnostic gene therapy approach aimed at stopping or slowing disease progression in patients affected by RCD.

5. withpower.com withpower.com/trial/phase-2-retinitis-1-2023-a1066

Gene Therapy with SPVN06 for Cone-Rod Dystrophy The treatment was found to be safe, with no serious adverse events related to the therapy, and 65% of participants in the intervention group achieved maximum ...

6. retinaldegenerationfund.org retinaldegenerationfund.org/news/news-posts/sparingvision-presents-initial-spvn06-safety-data-at-the-macula-society-47th-annual-meeting/

SparingVision Presents Initial SPVN06 Safety Data at the ... Initial six-month data on the three patients who received a low dose of SPVN06 showed no serious adverse events, significant inflammation, discontinuation, or ...

7. cgtlive.com cgtlive.com/view/rod-cone-dystrophy-gene-therapy-demonstrates-acceptable-safety-study-to-continue

Rod-Cone Dystrophy Gene Therapy Demonstrates ... SPVN06 (SparingVision) gene therapy had a manageable safety profile in patients with rod-cone dystrophy (RCD). A data safety monitoring ...