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Safety and Tolerability of VGR-R01 in Patients With Bietti Crystalline Dystrophy

Primary Purpose

Bietti Crystalline Dystrophy

Status
Recruiting
Phase
Early Phase 1
Locations
China
Study Type
Interventional
Intervention
VGR-R01
Sponsored by
Beijing Tongren Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bietti Crystalline Dystrophy

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. ≥18 years and <80 years of age;
  2. Confirmed diagnosis of Bietti Crystalline Dystrophy;
  3. Molecular diagnosis of CYP4v2 mutations (homozygotes or compound heterozygotes);
  4. BCVA ≤ 20/200 in the study eye;
  5. -8 D <diopters< +8 D, 21 mm < axial lengths ≤ 28 mm in the study eye;
  6. Normal liver function and renal function；
  7. Agree to use reliable barrier contraception for 1 year after administration of VGR-R01;
  8. Able to provide informed consent and comply with requirements of the study. -

Exclusion Criteria:

  1. Have insufficient viable retinal photoreceptor cells based on investigator's decision;
  2. Have current ocular or periocular infections, or endophthalmitis;
  3. Have any significant ocular disease/disorder other than BCD, including age-related macular degeneration, diabetic retinopathy, optic neuropathy, significant lens opacity, glaucoma, uveitis, retinal detachment, etc;
  4. Have intraocular surgery history except cataract surgery in the study eye;
  5. Prior medications which may interfere with the interpretation of study endpoints within six months before screening, eg. anti-VEGF drugs;
  6. Have or potentially require of systemic medications that may cause eye injure;
  7. Live attenuated vaccines is expected to be required during the study;
  8. Participation in a clinical study with an investigational drug or medical device within three months before enrollment;
  9. History of allergy or sensitivity to investigational drug, medications planned for use in the study;
  10. Use of anticoagulants, or after 10 days cessation of anti-platelet agents the platelet function does not recover;
  11. Use of any corticosteroids, other immunosuppressive drug(s) or antipsychotic drugs (eg. antidepressant, etc.) within 3 months prior to enrollment;
  12. Have contraindications for corticosteroids or immunosuppressant;
  13. Have complicating systemic diseases that would preclude the planned follow-up;
  14. Abnormal coagulation function or other clinically significant abnormal laboratory results;
  15. Have malignancies or history of malignancies;
  16. History of immunodeficiency (acquired or congenital);
  17. Females in lactation period;
  18. Have a history of alcohol or illicit drug addiction;
  19. Unable or unwilling to comply with the schedule of visits. -

Sites / Locations

  • Beijing Tongren HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

VGR-R01

Arm Description

Subretinal injection of VGR-R01

Outcomes

Primary Outcome Measures

Incidence of adverse events
An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a product; the event will not need to have a causal relationship with the treatment.
Incidence of serious adverse events
A serious adverse event (SAE) is any untoward medical occurrence at any dose that resulted in death; life threatening; require inpatient hospitalization or prolongation of existing hospitalization; result in persistent or significant disability/incapacity; result in congenital anomaly/birth defect.
Number of Participants with Clinically Significant Change from Baseline in Vital Signs
Vital signs (temperature, respiratory rate, pulse rate, systolic and diastolic blood pressure) will be obtained with participant in the seated position, after having sat calmly for at least 5 minutes. Clinical significance of vital signs will be determined at the investigator's discretion.
Number of Participants with Clinically Laboratory Abnormalities
Laboratory Tests will include hematology, coagulation, blood chemistry, urinalysis, serology, and pregnancy test, etc. If any potential changes accompanied by clinical symptoms, or results in a change of medical intervention, the findings will be considered as clinically significant based on investigator's decision.
Number of Participants with Clinically Significant Change from Baseline in Ophthalmic Examination Findings
Ophthalmic Examination will include BCVA, IOP, slitlamp examination, angiography and SD-OCT, etc. If any potential changes accompanied by clinical symptoms, or results in a change of medical intervention, the findings will be considered as clinically significant based on investigator's decision.

Secondary Outcome Measures

Best-Corrected Visual Acuity (BCVA)
BCVA will be assessed for both eyes using the Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart. BCVA test should be performed prior to pupil dilation, and distance refraction should be carried out before BCVA is measured. Initially, letters are read at a distance of 4 meters from the chart. If <20 letters are read at 4 meters, testing at 1 meter should be performed. BCVA is to be reported as number of letters read correctly by the participant using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved.
Changes from baseline in Visual Field indexes
The outcome measeures will be assessed by Humphery perimetry
Changes from baseline in Microperimetry indexes
The Microperimetry will be applied to assess the retinal sensitivity and the fixation behaviour.
Changes from baseline in ERG indexes
The measeurement will be performed based on the standards of International Society for Clinical Electrophysiology of Vision (ISCEV)
Changes from baseline in m-ERG indexes
The measeurement will be performed based on the standards of International Society for Clinical Electrophysiology of Vision (ISCEV)
Change from Baseline in NEI Visual Function Questionnaire (NEI-VFQ-25)
NEI-VFQ-25 questionnaire measures dimensions of self-reported vision-targeted health status that are most important to persons with eye disease. Total score ranges from 0-100, where a score of 0 represents the worst outcome and 100 represents the best outcome.
Changes from Baseline in Spectral Domain Optical Coherence Tomography (SD-OCT)
Changes from Baseline in Optical Coherence Tomography Angiography(OCT-A)

Full Information

First Posted
May 11, 2022
Last Updated
November 8, 2022
Sponsor
Beijing Tongren Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05399069
Brief Title
Safety and Tolerability of VGR-R01 in Patients With Bietti Crystalline Dystrophy
Official Title
An Open-Label Safety Study of Single-dose VGR-R01 in Patients With Bietti Crystalline Dystrophy
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Recruiting
Study Start Date
September 15, 2022 (Actual)
Primary Completion Date
May 2024 (Anticipated)
Study Completion Date
May 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Beijing Tongren Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
An Open-Label, Non-Randomized, Uncontrolled, Single-dose Pilot Study of VGR-R01 in Patients with Bietti Crystalline Dystrophy.
Detailed Description
VGR-R01 is a novel AAV vector carrying the human CYP4v2 coding sequence. This study is intended to evaluate the safety and tolerability of a single subretinal administration of VGR-R01. All subjects will undergo 365(±7) days of safety observation and will be encouraged to enroll in an extension study to evaluate the long-term safety of VGR-R01 for a total of five years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bietti Crystalline Dystrophy

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
VGR-R01
Arm Type
Experimental
Arm Description
Subretinal injection of VGR-R01
Intervention Type
Drug
Intervention Name(s)
VGR-R01
Intervention Description
Gene Replacement Therapy
Primary Outcome Measure Information:
Title
Incidence of adverse events
Description
An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a product; the event will not need to have a causal relationship with the treatment.
Time Frame
Baseline up to Day 365
Title
Incidence of serious adverse events
Description
A serious adverse event (SAE) is any untoward medical occurrence at any dose that resulted in death; life threatening; require inpatient hospitalization or prolongation of existing hospitalization; result in persistent or significant disability/incapacity; result in congenital anomaly/birth defect.
Time Frame
Baseline up to Day 365
Title
Number of Participants with Clinically Significant Change from Baseline in Vital Signs
Description
Vital signs (temperature, respiratory rate, pulse rate, systolic and diastolic blood pressure) will be obtained with participant in the seated position, after having sat calmly for at least 5 minutes. Clinical significance of vital signs will be determined at the investigator's discretion.
Time Frame
Baseline up to Day 365
Title
Number of Participants with Clinically Laboratory Abnormalities
Description
Laboratory Tests will include hematology, coagulation, blood chemistry, urinalysis, serology, and pregnancy test, etc. If any potential changes accompanied by clinical symptoms, or results in a change of medical intervention, the findings will be considered as clinically significant based on investigator's decision.
Time Frame
Baseline up to Day 365
Title
Number of Participants with Clinically Significant Change from Baseline in Ophthalmic Examination Findings
Description
Ophthalmic Examination will include BCVA, IOP, slitlamp examination, angiography and SD-OCT, etc. If any potential changes accompanied by clinical symptoms, or results in a change of medical intervention, the findings will be considered as clinically significant based on investigator's decision.
Time Frame
Baseline up to Day 365
Secondary Outcome Measure Information:
Title
Best-Corrected Visual Acuity (BCVA)
Description
BCVA will be assessed for both eyes using the Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart. BCVA test should be performed prior to pupil dilation, and distance refraction should be carried out before BCVA is measured. Initially, letters are read at a distance of 4 meters from the chart. If <20 letters are read at 4 meters, testing at 1 meter should be performed. BCVA is to be reported as number of letters read correctly by the participant using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved.
Time Frame
Up to Day 365
Title
Changes from baseline in Visual Field indexes
Description
The outcome measeures will be assessed by Humphery perimetry
Time Frame
Up to Day 365
Title
Changes from baseline in Microperimetry indexes
Description
The Microperimetry will be applied to assess the retinal sensitivity and the fixation behaviour.
Time Frame
Up to Day 365
Title
Changes from baseline in ERG indexes
Description
The measeurement will be performed based on the standards of International Society for Clinical Electrophysiology of Vision (ISCEV)
Time Frame
Up to Day 365
Title
Changes from baseline in m-ERG indexes
Description
The measeurement will be performed based on the standards of International Society for Clinical Electrophysiology of Vision (ISCEV)
Time Frame
Up to Day 365
Title
Change from Baseline in NEI Visual Function Questionnaire (NEI-VFQ-25)
Description
NEI-VFQ-25 questionnaire measures dimensions of self-reported vision-targeted health status that are most important to persons with eye disease. Total score ranges from 0-100, where a score of 0 represents the worst outcome and 100 represents the best outcome.
Time Frame
Up to Day 365
Title
Changes from Baseline in Spectral Domain Optical Coherence Tomography (SD-OCT)
Time Frame
Up to Day 365
Title
Changes from Baseline in Optical Coherence Tomography Angiography(OCT-A)
Time Frame
Up to Day 365

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: ≥18 years and <80 years of age; Confirmed diagnosis of Bietti Crystalline Dystrophy; Molecular diagnosis of CYP4v2 mutations (homozygotes or compound heterozygotes); BCVA ≤ 20/200 in the study eye; -8 D <diopters< +8 D, 21 mm < axial lengths ≤ 28 mm in the study eye; Normal liver function and renal function； Agree to use reliable barrier contraception for 1 year after administration of VGR-R01; Able to provide informed consent and comply with requirements of the study. - Exclusion Criteria: Have insufficient viable retinal photoreceptor cells based on investigator's decision; Have current ocular or periocular infections, or endophthalmitis; Have any significant ocular disease/disorder other than BCD, including age-related macular degeneration, diabetic retinopathy, optic neuropathy, significant lens opacity, glaucoma, uveitis, retinal detachment, etc; Have intraocular surgery history except cataract surgery in the study eye; Prior medications which may interfere with the interpretation of study endpoints within six months before screening, eg. anti-VEGF drugs; Have or potentially require of systemic medications that may cause eye injure; Live attenuated vaccines is expected to be required during the study; Participation in a clinical study with an investigational drug or medical device within three months before enrollment; History of allergy or sensitivity to investigational drug, medications planned for use in the study; Use of anticoagulants, or after 10 days cessation of anti-platelet agents the platelet function does not recover; Use of any corticosteroids, other immunosuppressive drug(s) or antipsychotic drugs (eg. antidepressant, etc.) within 3 months prior to enrollment; Have contraindications for corticosteroids or immunosuppressant; Have complicating systemic diseases that would preclude the planned follow-up; Abnormal coagulation function or other clinically significant abnormal laboratory results; Have malignancies or history of malignancies; History of immunodeficiency (acquired or congenital); Females in lactation period; Have a history of alcohol or illicit drug addiction; Unable or unwilling to comply with the schedule of visits. -
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wenbin Wei
Phone
010-58269516
Email
tr_weiwenbin@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Xiuli Zhao
Phone
010-58268486-8008
Email
xiulizhao@medmail.com.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wenbin Wei
Organizational Affiliation
Vice President of Beijing Tongren Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beijing Tongren Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100730
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wen-Bin Wei, MD
Email
weiwenbintr@163.com
First Name & Middle Initial & Last Name & Degree
Wen-Bin Wei, MD
First Name & Middle Initial & Last Name & Degree
Xiu-Li Zhao, PhD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
IPD will be shared with other researchers when VGR-R01 is fully approved.
IPD Sharing Time Frame
IPD will be shared with other researchers when VGR-R01 is fully approved.
IPD Sharing Access Criteria
IPD will be shared with other researchers when VGR-R01 is fully approved.

Learn more about this trial

Safety and Tolerability of VGR-R01 in Patients With Bietti Crystalline Dystrophy

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