A Study of Two Doses of VP-001 Administered Intravitreally in Participants with Confirmed PRPF31 Mutation-Associated Retinal Dystrophy Previously Treated with VP001

Phase 1

Not yet recruiting

• Conditions: Retinitis Pigmentosa 11; Eye Diseases Hereditary; Retinal Dystrophies; Retinal Degeneration; Retinal Disease
• Interventions: Drug: VP-001

• Registration Number: NCT06852963
• Lead Sponsor: PYC Therapeutics

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-02-20
• Study First Submitted QC: 2025-02-24
• Study First Posted: 2025-02-28
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-02
• Last Update Posted: 2025-03-05
• Study Start: 2025-06-01
• Primary Completion: 2027-06-01
• Study Completion: 2027-08-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

• Male or female sex; ≥18 years of age at Day 1/Baseline (Visit 2)
• 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
• Must have been previously enrolled in PLATYPUS Part B (Protocol #VP001-CL101) or WALLABY (Protocol #VP001-CL102) study. At Screening Visit in this study, participants must have completed at least 8 weeks after last study agent administration in PLATYPUS Part B (Protocol #VP001-CL101) or WALLABY (Protocol # VP001-CL102) study
• Have a confirmed clinical diagnosis of Retinitis Pigmentosa.
• Have a confirmed genetic diagnosis of Retinitis Pigmentosa secondary to mutation in the PRPF31 gene.
• 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 non-sexually 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 post-menopausal (12 months after last menses).

Exclusion Criteria

• 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.
• Known mutations in genes that cause autosomal dominant RP, X-linked RP, or presence of biallelic mutations in autosomal recessive RP/retinal dystrophy genes other than PRPF31 mutations.
• Have used anti-VEGF agents within 2 months or corticosteroid injections within the last 3 months.
• Have had Ozurdex® implants placed within 3 months or Retisert® or Iluvien® implants placed within 3 years prior to Baseline (Visit 2).
• 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.
• Have ocular media opacity or poor pupillary dilation prohibiting quality ophthalmic evaluation or photography, as assessed by the investigator.
• 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.
• 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; IUD; or surgical sterilization of partner. For non-sexually 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 post-menopausal (12 months after last menses).
• Have a recent history (<6 months) or current excessive recreational drug or alcohol use, in the opinion of the investigator.
• Any retinal pathology other than RP11 that in the investigator's opinion could affect study results.
• 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1: 120ug VP-001 every 8 weeks	VP-001	treated with 120ug of VP-001, administered IVT, every 8 weeks
Cohort 2: 120ug of VP-001 every 12 weeks	VP-001	treated with 120ug of VP-001, administered IVT, every 12 weeks
Cohort 3: 75ug of VP-001 every 8 weeks	VP-001	treated with 75ug of VP-001, administered IVT, every 8 weeks
Cohort 4: 75ug of VP-001 every 12 weeks	VP-001	treated with 75ug of VP-001, administered IVT, every 12 weeks

Primary Outcome Measures

Name	Time	Method
To determine the safety of two doses and two dosing regimens of repeatedly administered intravitreally VP-001 in participants with confirmed PRPF31 mutation-associated retinal dystrophy	24 months	The incidence, severity, and relatedness of ocular TEAEs and TE-SAEs in the study eye over a 24-month time period for each of the repeat doses

Secondary Outcome Measures

Name	Time	Method
To determine the change from Baseline (Visit 2) through End of Study/Early Termination in BCVA letter score using ETDRS charts	24 months	This is to determine the efficacy of two doses and two dosing regimes of repeatedly administered intravitreally VP-001 in participants with confirmed PRPF31 mutation-associated retinal dystrophy.; A gain of Early Treatment Diabetic Retinopathy Study (ETDRS) letters in Best-Corrected Visual Acuity (BCVA) from Baseline through EOS/ET would indicate vision improvement.
To determine the change from baseline (Visit 2) through End of Study/Early Termination in Low Luminance Visual Acuity letter score	24 months	\> to determine the efficacy of two doses and two dosing regimens of repeatedly administered intravitreally VP-001 in participants with confirmed PRPF31 mutation-associated retinal dystrophy
Change from Baseline (Visit 2) through End of Study/Early Termination in visual field sensitivity	24 months	Mean deviation (Mean Defect) as measured by standard static perimetry (Humphries)
Change from Baseline (Visit 2) through End of Study/Early Termination in mean retinal sensitivity	24 months	* to determine the efficacy of two doses and two dosing regimens of repeatedly administered intravitreally VP-001 in participants with confirmed PRPF31 mutation-associated retinal dystrophy.; * mean retinal sensitivity will be measured by fundus-guided microperimetry, measured in dB (Decibels).
Change from Baseline (Visit 2) through End of Study/Early Termination in preserved EZ area on SD-OCT	24 months	SD-OCT refers to Spectral Domain Optical Coherence Tomography. A preserved EZ area refers to the region of the retina where the Ellipsoid Zone (EZ), a distinct hyperreflective band representing the inner segments of photoreceptor cells, remains intact and visible, indicating relatively healthy photoreceptor function, often measured in a specific area on the scan to monitor disease progression in conditions like retinitis pigmentosa.
Change from Baseline (Visit 2) through End of Study/Early Termination in participant reported outcome measures utilizing the Michigan Retinal Degeneration Questionnaire (MRDQ)	24 months	The Michigan Retinal Degeneration Questionnaire (MRDQ) is a psychometrically validated patient reported outcomes (PRO) measure for patients with inherited retinal degenerations.

Trial Locations

Locations (6)

University of Florida College of Medicine; 🇺🇸 Jacksonville, Florida, United States

Bascom Palmer Eye Institute - University of Miami; 🇺🇸 Miami, Florida, United States

Kellogg Eye Center - University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Casey Eye Institute - OHSU; 🇺🇸 Portland, Oregon, United States

Retina Foundation of the Southwest; 🇺🇸 Dallas, Texas, United States

Baylor College of Medicine; 🇺🇸 Houston, Texas, United States