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SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Platypus)

Primary Purpose

Retinal Dystrophy, PRPF31 Mutationassociated Retinal Dystrophy, RP11

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
VP-001
Sponsored by
PYC Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Retinal Dystrophy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Male or female sex; ≥ 18 years of age at Baseline (Visit 2). Have a molecular (genetic) diagnosis of PRPF31 mutation. 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. 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. Are willing to comply with the instructions and attend all scheduled study visits. 6. Have light perception (LP) or better vision in the study eye. 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 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. 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-vascular endothelial growth factor (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. Have received any prior cell or gene therapy for a retinal condition. 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.

Sites / Locations

  • Retina Foundation of the SouthwestRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single arm dose escalation study of VP-001

Arm Description

Outcomes

Primary Outcome Measures

The incidence, severity, and relatedness of treatment-emergent ocular adverse events (TEAEs) and treatment-emergent serious adverse events (TE-SAEs) in the study eye
The incidence, severity, and relatedness of treatment-emergent ocular adverse events (TEAEs) and treatment-emergent serious adverse events (TE-SAEs) in the study eye

Secondary Outcome Measures

Adverse Events and Treatment Emergent Serious adverse events (SAEs) in the fellow eye
Adverse Events and Treatment Emergent serious adverse events (SAEs) in the fellow eye
Incidence, severity relatedness and of non-ocular TEAEs
Incidence, severity relatedness and of non-ocular TEAEs

Full Information

First Posted
May 25, 2023
Last Updated
June 30, 2023
Sponsor
PYC Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT05902962
Brief Title
SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
Acronym
Platypus
Official Title
A Phase 1 Open-Label, Single Arm Dose Escalation Study to Evaluate the Safety and Tolerability of Intravitreally Administered VP-001 in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 20, 2023 (Actual)
Primary Completion Date
April 30, 2024 (Anticipated)
Study Completion Date
April 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
PYC Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Retinal Dystrophy, PRPF31 Mutationassociated Retinal Dystrophy, RP11

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Single arm dose escalation study of VP-001
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
VP-001
Intervention Description
Phase 1 open-label, single arm dose escalation study of VP-001 in participants with genetically confirmed PRPF31 mutation-associated retinal dystrophy
Primary Outcome Measure Information:
Title
The incidence, severity, and relatedness of treatment-emergent ocular adverse events (TEAEs) and treatment-emergent serious adverse events (TE-SAEs) in the study eye
Time Frame
over a 24-week time period
Title
The incidence, severity, and relatedness of treatment-emergent ocular adverse events (TEAEs) and treatment-emergent serious adverse events (TE-SAEs) in the study eye
Time Frame
over a 48-week time period
Secondary Outcome Measure Information:
Title
Adverse Events and Treatment Emergent Serious adverse events (SAEs) in the fellow eye
Time Frame
over a 24-week time period
Title
Adverse Events and Treatment Emergent serious adverse events (SAEs) in the fellow eye
Time Frame
over a 48-week time period
Title
Incidence, severity relatedness and of non-ocular TEAEs
Time Frame
over a 24-week time period
Title
Incidence, severity relatedness and of non-ocular TEAEs
Time Frame
over a 48-week time period
Other Pre-specified Outcome Measures:
Title
Change from Baseline in Best-corrected visual acuity (BCVA) letter score using Early Treatment Diabetic Retinopathy Study (ETDRS) charts
Time Frame
over a 24-week time period
Title
Change from Baseline in Best-corrected visual acuity (BCVA) letter score using Early Treatment Diabetic Retinopathy Study (ETDRS) charts
Time Frame
over a 48-week time period
Title
Change from Baseline in lowest passing light level using Ora-VNC™ mobility test
Time Frame
over a 24-week time period
Title
Change from Baseline in lowest passing light level using Ora-VNC™ mobility test
Time Frame
over a 48-week time period
Title
Change from Baseline in Low luminance visual acuity (LLVA) letter score
Time Frame
over a 24-week time period
Title
Change from Baseline in Low luminance visual acuity (LLVA) letter score
Time Frame
over a 48-week time period
Title
Change from Baseline in Visual field sensitivity as measured by static perimetry with topographic analysis (Hill of Vision)
Time Frame
over a 24-week time period
Title
Change from Baseline in Visual field sensitivity as measured by static perimetry with topographic analysis (Hill of Vision)
Time Frame
over a 48-week time period
Title
Change from Baseline in Mean retinal sensitivity as measured by fundus-guided microperimetry
Time Frame
over a 24-week time period
Title
Change from Baseline in Mean retinal sensitivity as measured by fundus-guided microperimetry
Time Frame
over a 48-week time period
Title
Change from Baseline in Visual fields as measured by kinetic perimetry, utilizing I4e, III4e and V4e stimuli
Time Frame
over a 24-week time period
Title
Change from Baseline in Visual fields as measured by kinetic perimetry, utilizing I4e, III4e and V4e stimuli
Time Frame
over a 48-week time period
Title
Change from Baseline in Rod- and cone-mediated retinal function as measured by white, red and blue FST
Time Frame
over a 24-week time period
Title
Change from Baseline in Rod- and cone-mediated retinal function as measured by white, red and blue FST
Time Frame
over a 48-week time period
Title
Change from Baseline in Retinal thickness on SD-OCT, including retinal thickness in each ETDRS subfield and ellipsoid zone (EZ) area and volume
Time Frame
over a 24-week time period
Title
Change from Baseline in Retinal thickness on SD-OCT, including retinal thickness in each ETDRS subfield and ellipsoid zone (EZ) area and volume
Time Frame
over a 48-week time period
Title
Change from Baseline in Participant reported outcome measures utilizing the Patient Global Impressions of Change (PGI-C) and Patient Global Impressions of Severity (PGI-S)
Time Frame
over a 24-week time period
Title
Change from Baseline in Participant reported outcome measures utilizing the Patient Global Impressions of Change (PGI-C) and Patient Global Impressions of Severity (PGI-S)
Time Frame
over a 48-week time period
Title
Change from Baseline in Retinal function using full-field electroretinography (ERG)
Time Frame
over a 24-week time period
Title
Change from Baseline in Retinal function using full-field electroretinography (ERG)
Time Frame
over a 48-week time period
Title
Change from Baseline in Area of hypo-autofluorescence captured by FAF
Time Frame
over a 24-week time period
Title
Change from Baseline in Area of hypo-autofluorescence captured by FAF
Time Frame
over a 48-week time period
Title
Change from Baseline in Abnormalities captured by wide-field fundus photography
Time Frame
over a 24-week time period
Title
Change from Baseline in Abnormalities captured by wide-field fundus photography
Time Frame
over a 48-week time period

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female sex; ≥ 18 years of age at Baseline (Visit 2). Have a molecular (genetic) diagnosis of PRPF31 mutation. 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. 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. Are willing to comply with the instructions and attend all scheduled study visits. 6. Have light perception (LP) or better vision in the study eye. 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 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. 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-vascular endothelial growth factor (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. Have received any prior cell or gene therapy for a retinal condition. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ora Inc
Phone
1-510-423-2680
Email
VP001@oraclinical.com
First Name & Middle Initial & Last Name or Official Title & Degree
Clare Guerrero
Phone
1-510-363-8576
Email
clare.guerrero@pyctx.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sreenivasu Mudumba
Organizational Affiliation
PYC
Official's Role
Study Chair
Facility Information:
Facility Name
Retina Foundation of the Southwest
City
Dallas
State/Province
Texas
ZIP/Postal Code
75321
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Martin Klein
Phone
214-363-3911
Ext
116
Email
mklein@retinafoundation.org
First Name & Middle Initial & Last Name & Degree
Kaylie Jones
Phone
214-363-3911
Ext
121
Email
kwebb@retinafoundation.org
First Name & Middle Initial & Last Name & Degree
David Birch, PhD

12. IPD Sharing Statement

Learn more about this trial

SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects

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