Safety Study of rAAV2/8-hCYP4V2 in Patients With Bietti's Crystalline Dystrophy (BCD)

Browse trials for

• Corneal Dystrophies, Hereditary 58
• Retinal Diseases 815

Corneal Dystrophies, Hereditary

58 studies on the registry are indexed under Corneal Dystrophies, Hereditary; 11 are open to participants now.

This study's planned enrollment of 12 is below the median of 24 across 38 interventional studies indexed under Corneal Dystrophies, Hereditary.

Lead sponsor

Beijing Tongren Hospital is the lead sponsor of 154 studies on the registry; 49 are open to participants now.

Study arms

• Experimental
  Single arm

  All patients enrolled in the study will receive a single subretinal injection of ZVS101e in one eye

  Drug: rAAV2/8-hCYP4V2

Interventions

• DrugrAAV2/8-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

  Also known as: ZVS101e, rAAV8-hCYP4V2

Primary outcomes

1. 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.

   Time frame: 24 months

2. 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

   Time frame: 24 months

3. 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).

   Time frame: 24 months

Secondary outcomes

1. 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

   Time frame: 24 months

2. Change from Baseline in visual field

   Visual field will be assessed by Humphrey perimetry, changes in VFI, MD, PSD will be analyzed.

   Time frame: 24 months

3. Change from Baseline in contrast sensitivity

   Change from baseline in contrast sensitivity will be measured using the CSV-1000E instrument.

   Time frame: 24 months

4. 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).

   Time frame: 24 months

5. 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.

   Time frame: 24 months

6. Change from Baseline in microperimetry

   Microperimetry will be measured using MP-3，changes in retinal light sensitivity will be analyzed.

   Time frame: 24 months

7. 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.

   Time frame: 24 months

8. Change from Baseline in retinal thickness

   Retinal thickness will be assessed for both eyes using OCT.

   Time frame: 24 months

9. 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.

   Time frame: 24 months

10. 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.

    Time frame: 24 months

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 ↗

Individual participant data

Plan to share: No