VP-001 for Retinal Dystrophy

(DINGO Trial)

Recruiting at 5 trial locations

Overseen By Jessica Dunne

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: PYC Therapeutics

Must not be taking: Anti-VEGF, Corticosteroids, Ozurdex

Disqualifiers: Uncontrolled systemic disease, Other RP mutations, others

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

Compensation: Varies

Number of Visits: 8

Duration: 24 months

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This is a repeat-dose, open-label, four arm safety and efficacy study of two doses of VP-001 administered intravitreally in participants with confirmed PRPF31 mutation-associated Retinal Dystrophy and previously treated with VP001.

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.

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

Valproic acid (VP-001) has been studied for safety in patients with retinitis pigmentosa, and these studies generally focus on its safety alongside its effectiveness. However, one study noted adverse effects on visual functions, indicating that while it has been used in humans, there may be some safety concerns to consider. ^{1 2 3 4 5}

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 improving visual function. Unlike other treatments, it is administered orally and has been studied for its long-term efficacy and safety in this condition. ^{1 2 3 4 6}

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. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with PRPF31 mutation-associated Retinal Dystrophy who have already been treated with VP-001. Specific eye conditions like fungal retinitis, Purtscher retinopathy, and other related diseases are the focus. Participants must meet certain health standards to be included.

Inclusion Criteria

I have Retinitis Pigmentosa due to a PRPF31 gene mutation.

Understand the language of the informed consent and are willing and able to provide written informed consent prior to any study procedures

Are willing to comply with the instruction and attend all scheduled study visits

Exclusion Criteria

I have had eye surgery within the last 3 months.

Have a recent history (<6 months) or current excessive recreational drug or alcohol use, in the opinion of the investigator

I've had Ozurdex, Retisert, or Iluvien implants within the specified time frames.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive repeat doses of VP-001 intravitreally, with dosing regimens of either 75ug or 120ug every 8 or 12 weeks

24 months

Every 8 or 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• VP-001

Trial Overview The study tests two doses of a drug called VP-001, given as an injection inside the eye (intravitreally). It's designed to see how safe and effective these doses are in treating specific types of inherited eye disorders.

How Is the Trial Designed?

Group I: Cohort 4: 75ug of VP-001 every 12 weeks Experimental Treatment 1 Intervention

treated with 75ug of VP-001, administered IVT, every 12 weeks

Group II: Cohort 3: 75ug of VP-001 every 8 weeks Experimental Treatment 1 Intervention

treated with 75ug of VP-001, administered IVT, every 8 weeks

Group III: Cohort 2: 120ug of VP-001 every 12 weeks Experimental Treatment 1 Intervention

treated with 120ug of VP-001, administered IVT, every 12 weeks

Group IV: Cohort 1: 120ug VP-001 every 8 weeks Experimental Treatment 1 Intervention

treated with 120ug of VP-001, administered IVT, every 8 weeks

Who Is Running the Clinical Trial?

PYC Therapeutics

Lead Sponsor

Trials

7

Recruited

170+

Published Research Related to This Trial

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]

Citations

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]