MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)

A Phase 1 Open-Label, Multiple Ascending Dose Study to Evaluate the Safety and Tolerability of Intravitreally Administered VP-001 in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy

A Phase 1 Open-Label, Multiple Ascending Dose Study to Evaluate the Safety and Tolerability of Intravitreally Administered VP-001 in Participants with Confirmed PRPF31 Mutation-Associated Retinal Dystrophy

Study Overview

• Status: Completed
• Conditions: Eye Diseases; Retinal Degeneration; Retinal Dystrophies; Retinal Disease; Retinitis Pigmentosa 11
• Intervention / Treatment: Drug: VP-001

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32209
      • University of Florida Health
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • University of Michigan Kellogg Eye Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University - Casey Eye Institute
  • Texas
    • Dallas, Texas, United States, 75321
      • Retina Foundation of the Southwest
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine- Alkek Eye Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female sex; ≥12 years of age at Baseline (Visit 2).
2. Have a molecular (genetic) diagnosis of PRPF31 mutation.
3. Have a clinical diagnosis of PRPF31 mutation-associated retinal dystrophy, that is, RP11. The following conditions are allowed for inclusion if due to RP11, if in the opinion of the investigator they will not interfere with study evaluations or have resolved: macular edema (intraretinal, sub-retinal or other fluid) requiring regular treatment at a frequency of less than every 6 weeks; macular edema must be stable for at least 3 months prior to Screening (Visit 1). The investigator must consult with the study Medical Monitor.
4. If ≥18 years of age, understand the language of the informed consent and are willing and able to provide written informed consent prior to any study procedures. If a minor (12 to <18 years of age), a parent or legal guardian willing and able to provide written permission for the minor's participation prior to performing any study related procedures and pediatric participant able to provide age appropriate assent for study participation.
5. If ≥18 years of age, are willing to comply with the instructions and attend all scheduled study visits. If a minor (12 to <18 years of age), able to complete all study assessments, comply with the protocol, and has a parent or caregiver willing and able to follow study instructions and attend study visits with the participant as required, in the opinion of the Investigator.

6. Meets ≥1 of the following for visual function in the study eye:

   1. V4e visual field >1000 deg2, per kinetic perimetry
   2. <Mean microperimetry threshold: >5 decibel (dB) to <15dB
   3. Visual acuity: 20/40 to 20/200 inclusive (>35 and <70 letters by Early-Treatment Diabetic Retinopathy Study [ETDRS])
   4. Ellipsoid zone (EZ) length >1000 microns, of which 500 microns is contiguous, by SD-OCT
   5. FST baseline no worse than -20 dB
7. Participants of childbearing potential and male participants must not be pregnant or lactating and must be sexually inactive by abstinence, which is consistent with the preferred and usual lifestyle of the participant or agree to use adequate birth control throughout study duration. Adequate birth control is defined as hormonal - oral, implantable, injectable, or transdermal contraceptives; mechanical - spermicide in conjunction with a barrier such as a condom or diaphragm; intrauterine device (IUD); or surgical sterilization of partner. For nonsexually active participants, abstinence may be regarded as an adequate method of birth control. Participants of childbearing potential include all participants who have experienced menarche and have not undergone successful surgical sterilization (bilateral tubal ligation, hysterectomy, or bilateral oophorectomy) or are not postmenopausal (12 months after last menses).

Exclusion Criteria:

1. Have any uncontrolled systemic disease that, in the opinion of the Investigator, would preclude participation in the study that include but are not limited to infection, uncontrolled elevated blood pressure, cardiovascular disease, or glycemic control issues, or any other medical condition that may put the participant at risk due to study procedures.
2. Mutations in genes that cause autosomal dominant RP, Xlinked RP, or presence of biallelic mutations in autosomal recessive RP/retinal dystrophy genes other than PRPF31 mutations.
3. Have used anti-vascular endothelial growth factor (VEGF) agents within 2 months or corticosteroid injections within the last 3 months.

4. Have had Ozurdex

   • implants placed within 3 months or Retisert
   • or Iluvien
   • implants placed within 3 years prior to Baseline (Visit 2).
5. Within 3 months prior to Baseline (Visit 2), have undergone any vitreoretinal surgery (scleral buckle, pars plana vitrectomy, retrieval of a dropped nucleus or intraocular lens, radial optic neurotomy, sheathotomy, cyclodestructive procedures or multiple filtration surgeries [2 or more]) or any other ocular surgery.
6. Have ocular media opacity or poor pupillary dilation prohibiting quality ophthalmic evaluation or photography, as assessed by the investigator.
7. Have used any investigational drug or device within 90 days or 5 estimated half-lives of Baseline (Visit 2), whichever is longer, or plan to participate in another study of drug or device during the study period. Participation in observational trials is allowable based on investigator discretion and consultation with the Medical Monitor. It is assumed that the observational trial evaluations would not interfere with participation in this study.
8. Have received any prior cell, ribonucleic acid (RNA) (including VP-001), or gene therapy for a retinal condition.
9. Have a recent history (<6 months) or current excessive recreational drug or alcohol use, in the opinion of the investigator.
10. Any retinal pathology other than RP11 that in the investigator's opinion could affect study results.
11. Participants should not have any conditions, in the investigator's opinion, that may put the participant at increased risk, confound study data, or interfere significantly with the participant's study participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Multi-ascending dose escalation study of VP-001	Drug: VP-001; A Phase 1 Open-Label, Multiple Ascending Dose Study of VP-001 in Participants with Confirmed PRPF31 Mutation- Associated Retinal Dystrophy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The incidence, severity, and relatedness of treatment-emergent ocular adverse events and treatment-emergent serious adverse events	over a 4-week post-dose period
The incidence, severity, and relatedness of treatment-emergent ocular adverse events	over a 52-week period

Secondary Outcome Measures

Outcome Measure	Time Frame
Adverse Events and Treatment Emergent serious adverse events (TESAEs) in the fellow eye eye	over a 4-week post-dose time period
Adverse Events and Treatment Emergent serious adverse events (TESAEs) in the fellow eye eye	over a 52-week period
Incidence, severity, and relatedness of non-ocular Treatment Emergent adverse events (TEAEs)	over a 4-week post-dose time period
Incidence, severity, and relatedness of non-ocular Treatment Emergent adverse events (TEAEs)	over a 52-week period
BCVA letter score using ETDRS charts	over a 52-week period
Change in lowest passing light level using Ora- VNC™ mobility test	over a 52-week period
Low luminance visual acuity (LLVA) letter score	over a 52-week period
Visual field sensitivity as measured by static perimetry with topographic analysis (Hill of Vision)	over a 52-week period
Mean retinal sensitivity as measured by fundusguided microperimetry	over a 52-week period
Visual fields as measured by kinetic perimetry utilizing I4e, II4e and V4e stimuli	over a 52-week period
Rod-and cone-mediated retinal function as measured by white, red and blue FST	over a 52-week period
Retinal thickness on SD-OCT, including retinal thickness in each ETDRS subfield and EZ area and volume	over a 52-week period
Retinal function using full-field electroretinography (ERG)	over a 52-week period
Area of hypo-autofluorescence captured by FAF	over a 52-week period
Abnormalities captured by wide-field fundus photography	over a 52-week period

Collaborators and Investigators

• Sponsor: PYC Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2024
• Primary Completion (Actual): September 24, 2025
• Study Completion (Actual): September 24, 2025

Study Registration Dates

• First Submitted: June 3, 2024
• First Submitted That Met QC Criteria: June 6, 2024
• First Posted (Actual): June 12, 2024

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases, Hereditary; Retinal Diseases; Eye Diseases; Retinal Degeneration; Retinal Dystrophies; Retinitis Pigmentosa 11
• Other Study ID Numbers: VP001-CL102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No