Bietti's Crystalline DystrophyEarly Phase 1NCT04722107
Safety Study of rAAV2/8-hCYP4V2 in Patients With Bietti's Crystalline Dystrophy (BCD)
A Early Phase 1 study testing rAAV2/8-hCYP4V2 in people with Bietti's Crystalline Dystrophy, run by Beijing Tongren Hospital at 1 site in China.
Trial summary
Primary Objectives: To evaluate the safety of rAAV2/8-hCYP4V2 gene replacement therapy drug administered as a single subretinal injection in patients with Bietti's Crystalline Dystrophy (BCD). Secondary Objectives: To preliminarily explore the clinical effectiveness of rAAV2/8-hCYP4V2 gene replacement therapy drugs. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bietti's Crystalline Dystrophy
- What is being tested?
- rAAV2/8-hCYP4V2
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteChina
- Study dates
- 21 Apr 2021to 29 Apr 2024
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1) Age ≥ 18 years old at the time of informed consent ;
- 2) Patients with a clinical diagnosis of Bietti's crystalline dystrophy (BCD);
- 3) Genetic test confirmed to carry two pathogenic variants of CYP4V2;
- 4) Meet the following target eye selection criteria： Best corrected visual acuity between 2.3 LogMAR and 0.5 LogMAR (including 2.3 LogMAR and 0.5 LogMAR, equivalent to Snellen visual acuity of hand move to 20/63); No refractive media clouding affecting fundus examination, visual examination and retinal function examination; The eye with the poorer visual acuity of the two eyes of the subject is the target eye. Note: For all subjects, only one eye will be used as the "target eye". If both eyes meet the inclusion criteria and the visual acuity is comparable, the target eye will be determined medically by the investigator.
- 5) Agree to take effective contraceptive measures from the beginning of the study to 2 year after the administration;
- 6) Voluntarily participate in this clinical trial and have signed the informed consent form.
Who cannot join
- 1) Patients lack sufficient retinal photoreceptors, retinal photoreceptors less than 1 optic disc area or retinal thickness less than 100 μm in the macula；
- 2) Existing or pre-existing of choroidal neovascular (CNV) lesions that were secondary to BCD, or other eye conditions interfering（ (e.g., high refractive error, retinal vasculitis, etc.) ） that may prevent surgery or interfere with the interpretation of the study endpoint;
- 3) Prior use of medicines which may affect the experimental observation within the 6 months before screening (such as ranibizumab, bevacizumab, aflibercept, conbercept)；
- 4) Prior intraocular surgery in the target eye (e.g. PDT, pars plana vitrectomy, retinal laser therapy )
- 5) Currently taking or may require systemic medications that can cause ocular toxicity, such as psoralen, risedronate, or tamoxifen；
- 6) Allergic constitution (such as those who are allergic to two or more drugs and foods);
Show all 13Show fewer
- 7) Abnormal physical examination, vital signs, laboratory tests (blood routine, urine routine, blood biochemistry, coagulation function, immunological examination, female blood pregnancy), 12-lead ECG, X-ray chest radiograph findings with any clinically significant abnormality, and where participation in this study may increase the subject's risk or interfere with data interpretation as assessed by the investigator；
- 8) Having any past or present medical history that may affect the safety of the trial or the in vivo process of the drug, especially the medical history of cardiovascular, hepatic, renal, endocrine, gastrointestinal, pulmonary, neurological, hematological, oncologic, immunological or metabolic disorders and others that are thought clinically significant by the investigator；
- 9) Participation in any medicine or medical device clinical trials within 3 months prior to enrollment;;
- 10) Neutralizing antibodies to rAAV> 1:1000 by immunologic test;
- 11) For females in pregnancy or lactation period;
- 12)Carrying other ophthalmic pathogenic mutations
- 13) Any other conditions which leads the investigator to determine the participant is unsuitable for this study.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Beijing Tongren Hospital
Beijing, Beijing Municipality, 100730
wenbin wei, Doctor, 13701255115, tr_weiwenbin@163.com
About this study
Official title: Safety Trial of rAAV2/8-hCYP4V2 Gene Replacement Therapy Drug Administered as a Single Subretinal Injection in Patients With Bietti's Crystalline Dystrophy (BCD)
Primary Objectives: To evaluate the safety of rAAV2/8-hCYP4V2 gene replacement therapy drug administered as a single subretinal injection in patients with Bietti's Crystalline Dystrophy (BCD).
Secondary Objectives: To preliminarily explore the clinical effectiveness of rAAV2/8-hCYP4V2 gene replacement therapy drugs.
Read the detailed description
This is a single-arm, open-label, and single-center study of ZVS101e in patients with BCD. A total of 12 participants will be enrolled. A retinal surgeon will administer the vector by subretinal injection. Safety, efficacy and vector shedding characteristics of ZVS101e are then measured over 2 years.
- Conditions
- Bietti's Crystalline Dystrophy
- Being tested
- rAAV2/8-hCYP4V2
- Medical subject headings
- Bietti Crystalline Dystrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rAAV2/8-hCYP4V2Drug
Also called ZVS101e, rAAV8-hCYP4V2
rAAV2/8-hCYP4V2 is developed by Chigenovo Co., Ltd., it contains recombinant adeno-associated virus serotype 8 (rAAV8) vectors which carry human CYP4V2 gene
| Study group | Role | What they receive |
|---|---|---|
| Single arm | Experimental | All patients enrolled in the study will receive a single subretinal injection of ZVS101e in one eye Receives: Drug: rAAV2/8-hCYP4V2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events
Incidence of adverse events, vital signs, physical examination, ophthalmic 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.
Measured: 24 months
Incidence of serious adverse events
A serious adverse event (SAE) is any untoward medical occurrence at any dose that leading to the following:
Results in death; Life-threatening, refers to an event in which the patient is at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe; Significant or permanent disability/incapacity, where disability refers to a serious disruption and damage of a person's ability to perform normal life functions; Requires inpatient hospitalization or prolongation of existing hospitalization; Congenital anomaly or birth defect; Other medically important events
Measured: 24 months
Clinically important changes from baseline after ZVS101e treatment
Clinically important changes including abnormal physical examinations, vital signs, ECG, laboratory findings (chemistry, hematology, urinalysis) and ophthalmologic findings (BCVA, slit lamp examination, ophthalmoscopy, IOP, funds photography, FAF, OCT, OCTA).
Measured: 24 months
Secondary outcomes (10)
Mean change from baseline in BCVA after ZVS101e treatment
BCVA of both eyes will be assessed using the early treatment of diabetic retinopathy study (ETDRS) chart
Measured: 24 months
Change from Baseline in visual field
Visual field will be assessed by Humphrey perimetry, changes in VFI, MD, PSD will be analyzed.
Measured: 24 months
Change from Baseline in contrast sensitivity
Change from baseline in contrast sensitivity will be measured using the CSV-1000E instrument.
Measured: 24 months
Change from Baseline in multi-luminance mobility test (MLMT)
MLMT was assessed at 1 or more of 7 levels of illumination, ranging from 400 lux (a brightly lit office) to 1 lux (a moonless summer night). The score range is between -1 (the worst) and 6 (the best).
Measured: 24 months
Change from Baseline in OCTA
The OCTA examines the retinal and choroidal vessels. The retinal and choroidal vessel perfusion area, vessel volume, and vessel index will be analyzed.
Measured: 24 months
Change from Baseline in microperimetry
Microperimetry will be measured using MP-3，changes in retinal light sensitivity will be analyzed.
Measured: 24 months
Change from Baseline in mfERG
The measurement will be performed based on the standards of international society for clinical electrophysiology of vision (ISCEV).The change of retinal function in the macula will be analyzed.
Measured: 24 months
Change from Baseline in retinal thickness
Retinal thickness will be assessed for both eyes using OCT.
Measured: 24 months
Change from Baseline in NEI VFQ-25 total score
National eye institute 25-item visual function questionnaire (NEI VFQ-25) consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs. All items are scored so that a high score represents better functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively.
Measured: 24 months
Change from Baseline in fundus autofluorescence (FAF)
FAF is a noninvasive test to explore the health and metabolic status of retinal pigment epithelial cell/photoreceptor complex.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2021
- Study start21 Apr 2021
- Primary completion25 Jan 2024 (estimated)
- Study completion29 Apr 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Bietti's Crystalline DystrophyStudies of the same condition, open and under way.
- More trials run by Beijing Tongren HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing Tongren Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- wenbin Wei, Doctor, Principal investigator, Vice President of Beijing Tongren Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04722107
- Sponsor's protocol ID
- ZVS101e-01
- Status last verified
- Jul 2022
- First submitted
- 11 Jan 2021
- Last updated
- 5 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Jia R, Meng X, Chen S, Zhang F, Du J, Liu X, Yang L. AAV-mediated gene-replacement therapy restores viability of BCD patient iPSC derived RPE cells and vision of Cyp4v3 knockout mice. Hum Mol Genet. 2023 Jan 1;32(1):122-138. doi: 10.1093/hmg/ddac181.
PubMed 35925866
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety Trial of rAAV2/8-hCYP4V2 Gene Replacement Therapy Drug Administered as a Single Subretinal Injection in Patients With Bietti's Crystalline Dystrophy (BCD)
- ClinicalTrials.gov ID
- NCT04722107
- Acronym / sponsor ID
- ZVS101e-01
- Conditions
- Bietti's Crystalline Dystrophy
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Beijing Tongren HospitalUniversity, hospital or other
- Study start
- 21 Apr 2021 (actual)
- Primary completion
- 25 Jan 2024 (estimated)
- Study completion
- 29 Apr 2024 (estimated)
- First posted
- 25 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary Objectives: To evaluate the safety of rAAV2/8-hCYP4V2 gene replacement therapy drug administered as a single subretinal injection in patients with Bietti's Crystalline Dystrophy (BCD).
Secondary Objectives: To preliminarily explore the clinical effectiveness of rAAV2/8-hCYP4V2 gene replacement therapy drugs.
Detailed description
This is a single-arm, open-label, and single-center study of ZVS101e in patients with BCD. A total of 12 participants will be enrolled. A retinal surgeon will administer the vector by subretinal injection. Safety, efficacy and vector shedding characteristics of ZVS101e are then measured over 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single arm | Experimental | Drug: rAAV2/8-hCYP4V2All patients enrolled in the study will receive a single subretinal injection of ZVS101e in one eye |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 1) Age ≥ 18 years old at the time of informed consent ;
- 2) Patients with a clinical diagnosis of Bietti's crystalline dystrophy (BCD);
- 3) Genetic test confirmed to carry two pathogenic variants of CYP4V2;
- 4) Meet the following target eye selection criteria： Best corrected visual acuity between 2.3 LogMAR and 0.5 LogMAR (including 2.3 LogMAR and 0.5 LogMAR, equivalent to Snellen visual acuity of hand move to 20/63); No refractive media clouding affecting fundus examination, visual examination and retinal function examination; The eye with the poorer visual acuity of the two eyes of the subject is the target eye. Note: For all subjects, only one eye will be used as the "target eye". If both eyes meet the inclusion criteria and the visual acuity is comparable, the target eye will be determined medically by the investigator.
- 5) Agree to take effective contraceptive measures from the beginning of the study to 2 year after the administration;
Key exclusion criteria (13 listed)
- 1) Patients lack sufficient retinal photoreceptors, retinal photoreceptors less than 1 optic disc area or retinal thickness less than 100 μm in the macula；
- 2) Existing or pre-existing of choroidal neovascular (CNV) lesions that were secondary to BCD, or other eye conditions interfering（ (e.g., high refractive error, retinal vasculitis, etc.) ） that may prevent surgery or interfere with the interpretation of the study endpoint;
- 3) Prior use of medicines which may affect the experimental observation within the 6 months before screening (such as ranibizumab, bevacizumab, aflibercept, conbercept)；
- 4) Prior intraocular surgery in the target eye (e.g. PDT, pars plana vitrectomy, retinal laser therapy )
- 5) Currently taking or may require systemic medications that can cause ocular toxicity, such as psoralen, risedronate, or tamoxifen；
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rAAV2/8-hCYP4V2Also: ZVS101e, rAAV8-hCYP4V2rAAV2/8-hCYP4V2 is developed by Chigenovo Co., Ltd., it contains recombinant adeno-associated virus serotype 8 (rAAV8) vectors which carry human CYP4V2 gene | Drug | Single arm |
Primary outcome
Incidence of adverse events
Time frame: 24 months
Incidence of adverse events, vital signs, physical examination, ophthalmic 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
Time frame: 24 months
A serious adverse event (SAE) is any untoward medical occurrence at any dose that leading to the following: Results in death; Life-threatening, refers to an event in which the patient is at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe; Significant or permanent disability/incapacity, where disability refers to a serious disruption and damage of a person's ability to perform normal life functions; Requires inpatient hospitalization or prolongation of existing hospitalization; Congenital anomaly or birth defect; Other medically important events
Clinically important changes from baseline after ZVS101e treatment
Time frame: 24 months
Clinically important changes including abnormal physical examinations, vital signs, ECG, laboratory findings (chemistry, hematology, urinalysis) and ophthalmologic findings (BCVA, slit lamp examination, ophthalmoscopy, IOP, funds photography, FAF, OCT, OCTA).
10 secondary outcomes
Mean change from baseline in BCVA after ZVS101e treatment
Time frame: 24 months
Change from Baseline in visual field
Time frame: 24 months
Change from Baseline in contrast sensitivity
Time frame: 24 months
Change from Baseline in multi-luminance mobility test (MLMT)
Time frame: 24 months
Change from Baseline in OCTA
Time frame: 24 months
Change from Baseline in microperimetry
Time frame: 24 months
Change from Baseline in mfERG
Time frame: 24 months
Change from Baseline in retinal thickness
Time frame: 24 months
Change from Baseline in NEI VFQ-25 total score
Time frame: 24 months
Change from Baseline in fundus autofluorescence (FAF)
Time frame: 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2023.
- Background: PubMed 35925866Jia R, Meng X, Chen S, Zhang F, Du J, Liu X, Yang L. AAV-mediated gene-replacement therapy restores viability of BCD patient iPSC derived RPE cells and vision of Cyp4v3 knockout mice. Hum Mol Genet. 2023 Jan 1;32(1):122-138. doi: 10.1093/hmg/ddac181.
- Individual participant dataSharing planned: No
Related trials for Bietti's Crystalline Dystrophy
Active, not recruitingPhase 3
Efficacy and Safety of ZVS101e in Patients With Bietti 's Crystalline Dystrophy
Bietti Crystalline Corneoretinal Dystrophy, Bietti Crystalline Dystrophy
Active, not recruitingEarly Phase 1
Safety and Tolerability of ZVS101e in Patients With Bietti 's Crystalline Dystrophy
Bietti's Crystalline Dystrophy
Not yet recruiting
ZVS101e in Patients With Bietti's Crystalline Dystrophy
Bietti's Crystalline Dystrophy, Bietti Crystalline Corneoretinal Dystrophy
Active, not recruitingEarly Phase 1
Safety and Efficacy Study of NGGT001 in Bietti Crystalline Corneoretinal Dystrophy
Bietti's Crystalline Dystrophy
Active, not recruitingPhase 1/2
Safety and Efficacy Study of NGGT001 in Bietti Crystalline Corneoretinal Dystrophy Subjects
Bietti Crystalline Corneoretinal Dystrophy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
wenbin Wei, Doctor principal investigator
Vice President of Beijing Tongren Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing rAAV2/8-hCYP4V2 in people with Bietti's Crystalline Dystrophy, run by Beijing Tongren Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 5 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact wenbin Wei, Doctor (13701255115, tr_weiwenbin@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of adverse events (time frame: 24 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04722107, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2023.