VP-001 for Retinal Dystrophy

(Platypus Trial)

Recruiting at 5 trial locations

Overseen By Clare Guerrero

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: PYC Therapeutics

Must not be taking: Anti-VEGF, Corticosteroid injections

Disqualifiers: Uncontrolled systemic disease, Other RP mutations, Recent ocular surgery, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have used anti-VEGF agents within 2 months or corticosteroid injections within the last 3 months before starting the trial.

What data supports the effectiveness of the drug VP-001 for Retinal Dystrophy?

Research on valproic acid (VPA), a component of VP-001, shows it has been studied for its potential to help with retinitis pigmentosa, a type of retinal dystrophy. Some studies suggest VPA might improve visual function in these patients. ^{1 2 3 4 5}

Is VP-001 (valproic acid) safe for humans?

Valproic acid (VP-001) has been studied for safety in people with retinitis pigmentosa, a type of retinal dystrophy. These studies generally focus on both the effectiveness and safety of the treatment, indicating that safety data is available for this condition. ^{1 2 3 6 7}

How is the drug VP-001 different from other treatments for retinal dystrophy?

VP-001, also known as valproic acid, is unique because it is being explored for its potential to treat retinal dystrophy, specifically retinitis pigmentosa, by possibly affecting visual function. Unlike other treatments, it is administered orally and has been studied for its long-term safety and efficacy in this condition. ^{1 2 3 4 6}

What is the purpose of this trial?

This trial tests a new eye injection treatment called VP-001 for people with a genetic condition that affects their vision. The goal is to see if it is safe and can help the damaged cells in their eyes.

Research Team

Sreenivasu Mudumba

Principal Investigator

PYC

Eligibility Criteria

Adults with a genetic diagnosis of PRPF31 mutation-associated retinal dystrophy (RP11) can join this trial. They must be willing to follow the study plan and attend all visits, use effective birth control if they can have children, and not be pregnant or breastfeeding. People with uncontrolled diseases, recent certain eye treatments or surgeries, other gene therapy for retinal conditions, or excessive drug/alcohol use cannot participate.

Inclusion Criteria

Have light perception (LP) or better vision in the study eye

Understand the language of the informed consent and willing to provide written informed consent

I have a genetic mutation in PRPF31.

Exclusion Criteria

I have cloudiness or poor dilation in my eye's pupil.

Conditions that may put the participant at increased risk or interfere with study participation

I have recently used anti-VEGF treatments or had corticosteroid injections or implants.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravitreal administration of VP-001 in a dose escalation manner to evaluate safety and tolerability

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• VP-001

Trial Overview The trial is testing VP-001 given as an injection into the eye to see if it's safe for people with RP11-related vision loss. It's an early-phase study where everyone gets the treatment but at different doses to find out which one is safest.

Participant Groups

Group I: Single arm dose escalation study of VP-001 Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

PYC Therapeutics

Lead Sponsor

Trials

7

Recruited

170+

Findings from Research

In a study of 13 eyes treated with valproic acid (VPA) for an average of 4 months, 9 eyes showed improved visual fields, resulting in a statistically significant average increase of 11% compared to baseline (p<0.02).

The treatment also led to a significant improvement in visual acuity, with an average decrease in logMAR scores indicating a change from approximately 20/47 to 20/32 (p<0.02), and side effects were mild and well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic potential of valproic acid for retinitis pigmentosa. Clemson, CM., Tzekov, R., Krebs, M., et al.[2022]

In a study of 24 patients with retinitis pigmentosa treated with valproic acid (VPA) for an average of 9.4 months, there was no significant improvement in best-corrected visual acuity (BCVA) or visual field analyses after treatment.

VPA treatment was associated with a decline in certain electroretinography (ERG) parameters, indicating potential negative effects, leading to the recommendation that VPA should not be prescribed for retinitis pigmentosa until further safety and efficacy evaluations are conducted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The adverse effects of valproic acid on visual functions in the treatment of retinitis pigmentosa. Totan, Y., Güler, E., Yüce, A., et al.[2018]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Long-term follow-up for efficacy and safety of treatment of retinitis pigmentosa with valproic acid. [2013]

2. England pubmed.ncbi.nlm.nih.gov

Therapeutic potential of valproic acid for retinitis pigmentosa. [2022]

3. India pubmed.ncbi.nlm.nih.gov

The adverse effects of valproic acid on visual functions in the treatment of retinitis pigmentosa. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Efficacy of oral valproic acid in patients with retinitis pigmentosa. [2014]

5. China pubmed.ncbi.nlm.nih.gov

Valproic acid's effects on visual acuity in retinitis pigmentosa: a systemic review and Meta-analysis. [2020]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Efficacy of valproic acid for retinitis pigmentosa patients: a pilot study. [2020]

7. England 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. [2022]