Clinical trial NCT06455826: MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
Official title: 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 type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Retinitis Pigmentosa 11
Retinal Degeneration
Eye Diseases
Retinal Disease
Retinal Dystrophies
Lead sponsor: PYC Therapeutics
Sponsor class: INDUSTRY
First posted: 2024-06-12
Enrollment: 12
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Participants will be assigned sequentially to the VP-001 escalation dose (30 μg and 75 μg) groups. Participants will receive three repeat IVT injections of VP-001, 8 weeks apart, in the study eye.
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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.

Primary outcomes:
measure: The incidence, severity, and relatedness of treatment-emergent ocular adverse events and treatment-emergent serious adverse events
timeFrame: over a 4-week post-dose period
measure: The incidence, severity, and relatedness of treatment-emergent ocular adverse events
timeFrame: over a 52-week period
Secondary outcomes:
measure: Adverse Events and Treatment Emergent serious adverse events (TESAEs) in the fellow eye eye
timeFrame: over a 4-week post-dose time period
measure: Adverse Events and Treatment Emergent serious adverse events (TESAEs) in the fellow eye eye
timeFrame: over a 52-week period
measure: Incidence, severity, and relatedness of non-ocular Treatment Emergent adverse events (TEAEs)
timeFrame: over a 4-week post-dose time period
measure: Incidence, severity, and relatedness of non-ocular Treatment Emergent adverse events (TEAEs)
timeFrame: over a 52-week period
measure: BCVA letter score using ETDRS charts
timeFrame: over a 52-week period
measure: Change in lowest passing light level using Ora- VNC™ mobility test
timeFrame: over a 52-week period
measure: Low luminance visual acuity (LLVA) letter score
timeFrame: over a 52-week period
measure: Visual field sensitivity as measured by static perimetry with topographic analysis (Hill of Vision)
timeFrame: over a 52-week period
measure: Mean retinal sensitivity as measured by fundusguided microperimetry
timeFrame: over a 52-week period
measure: Visual fields as measured by kinetic perimetry utilizing I4e, II4e and V4e stimuli
timeFrame: over a 52-week period
measure: Rod-and cone-mediated retinal function as measured by white, red and blue FST
timeFrame: over a 52-week period
measure: Retinal thickness on SD-OCT, including retinal thickness in each ETDRS subfield and EZ area and volume
timeFrame: over a 52-week period
measure: Retinal function using full-field electroretinography (ERG)
timeFrame: over a 52-week period
measure: Area of hypo-autofluorescence captured by FAF
timeFrame: over a 52-week period
measure: Abnormalities captured by wide-field fundus photography
timeFrame: over a 52-week period
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: University of Florida Health
state: Florida
city: Ann Arbor
country: United States
facility: University of Michigan Kellogg Eye Center
state: Michigan
city: Portland
country: United States
facility: Oregon Health and Science University - Casey Eye Institute
state: Oregon
city: Dallas
country: United States
facility: Retina Foundation of the Southwest
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine- Alkek Eye Center
state: Texas
Study officials:
References: