Safety and Tolerability Study of Gene Editing Drug ZVS203e in Participants With Retinitis Pigmentosa

NCT05805007 | Recruiting Early Phase 1

• 1 other identifier: ZYB-2022-001
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety, tolerability and efficacy of a single escalating doses of ZVS203e administered via subretinal injection in participants with RP caused by RHO site-specific gene mutation (RHO-RP).

Conditions

Retinitis Pigmentosa

Keywords

gene editing; retinitis pigmentosa; RHO; rAAV

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events (AEs）

  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.

  Baseline up to Week 52

• Incidence of serious adverse events (SAEs)

  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.

  Baseline up to Week 52

Secondary Outcomes (9)

• Mean change from baseline in BCVA after ZVS203e treatment

  Baseline up to Week 52

• Change from Baseline in visual field

  Baseline up to Week 52

• Change from Baseline in contrast sensitivity

  Baseline up to Week 52

• Change from Baseline in multi-luminance mobility test (MLMT)

  Baseline up to Week 52

• Change from Baseline in retinal thickness

  Baseline up to Week 52

Study Arms (1)

Dose escalation

EXPERIMENTAL

Three cohorts of 3 patients each. All the patients enrolled in the study will receive a single subretinal injection in one eye. Cohort 1: Subretinal administration of a single low dose ZVS203e at Day 0. Cohort 2: Subretinal administration of a single medium dose ZVS203e at Day 0. Cohort 3: Subretinal administration of a single high dose ZVS203e at Day 0.

Drug: ZVS203e

Interventions

ZVS203e DRUG

ZVS203e is a rAAV-mediated gene editing drug that silences RHO mutant protein expression by CRISPR/Cas9 editing system.

Dose escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Patients with clinical diagnosis of Retinitis Pigmentosa (RP) (age ≥ 18 years) ;
• \. Genetic test confirmed to carry a fix mutation of RHO and carry no pathogenic mutations of other ophthalmic genetic diseases;
• \. 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) ;
• \. Agree to take effective contraceptive measures from the beginning of the study to 1 year after the administration;
• Willingness to adhere to protocol as evidenced by written informed consent;

You may not qualify if:

• \. Existing or pre-existing of macular lesions such as retinoschisis or macular membrane, or other eye conditions interfering with the surgery or the interpretation of the clinical endpoint, in the investigators' opinion;
• \. The study eye has been treated with other drugs within 3 months that could affect the evaluation of the investigational drug;
• \. The study eye has been treated with the following intraocular procedures: retinal detachment surgery, vitrectomy;
• \. The presence of an ocular/visual disease, disorder or lesion known to cause, or to be associated with, vision loss, or whose associated treatment or therapy is known to cause, or to be associated with, vision loss；
• \. Currently taking or may require systemic medications that can cause ocular toxicity, such as psoralen, risedronate, or tamoxifen;
• \. Known allergy to the drug planned for use in the study；
• Those with the following laboratory abnormalities which are clinically significant: Liver function: chronic liver disease, ALT increased \>2 times the upper limit of normal; With uncontrolled hypertension, mean systolic blood pressure ≥ 160 mmHg or mean diastolic blood pressure ≥ 100 mmHg; With uncontrolled diabetes, HbA1c\>10%; Patients with abnormal coagulation function (prothrombin time ≥ upper limit of normal (3 seconds' longer), activated partial thromboplastin time ≥ upper limit of normal (10 seconds' longer)); Serum virology test: Active hepatitis B, hepatitis C virus antibody (HCV-Ab), human immunodeficiency virus antibody (HIV-Ab) or syphilis antibody positive;
• \. 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；
• \. Participation in any medicine or medical device clinical trials within 3 months prior to enrollment;
• \. Neutralizing antibodies to rAAV\> 1:1000 by immunologic test;
• \. For females in pregnancy or lactation period;
• \. Any other conditions which leads the investigator to determine the participant is unsuitable for this study.

Sponsors & Collaborators

• Peking University Third Hospital: lead

Study Sites (1)

Peking University Third Hospital

Beijing, Beijing Municipality, 100191, China

RECRUITING

MeSH Terms

Conditions

Retinitis Pigmentosa

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Retinal Dystrophies; Retinal Degeneration; Retinal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Liping Yang, MD

  Peking University Third Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Liping Yang, MD

CONTACT

010-82266595; alexlipingyang@bjmu.edu.cn

Jinlu Zhang, MD

CONTACT

15810570898; zhangjinlu@bjmu.edu.cn

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2023
• First Posted: April 7, 2023
• Study Start: September 12, 2023
• Primary Completion: April 1, 2026
• Study Completion: April 1, 2026
• Last Updated: October 24, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)