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

NCT ID: NCT05805007

Last Updated: 2023-10-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-12
• Study Completion Date: 2026-04-30

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).

Detailed Description

This is a single-arm, open-label, single ascending dose study of ZVS203e in participants with RHO-RP. Up to 9 participants will be enrolled in this study. Safety, efficacy and vector shedding characteristics of ZVS203e are then measured.

Conditions

Retinitis Pigmentosa

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose escalation

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.

Group Type: EXPERIMENTAL

ZVS203e

Intervention Type: DRUG

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

Interventions

ZVS203e

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 1. Patients with clinical diagnosis of Retinitis Pigmentosa (RP) (age ≥ 18 years) ;
• 2. Genetic test confirmed to carry a fix mutation of RHO and carry no pathogenic mutations of other ophthalmic genetic diseases;
• 3. 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) ;
• 4. Agree to take effective contraceptive measures from the beginning of the study to 1 year after the administration;
• 5.Willingness to adhere to protocol as evidenced by written informed consent;

Exclusion Criteria

• 1. 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;
• 2. The study eye has been treated with other drugs within 3 months that could affect the evaluation of the investigational drug;
• 3. The study eye has been treated with the following intraocular procedures: retinal detachment surgery, vitrectomy;
• 4. 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；
• 5. Currently taking or may require systemic medications that can cause ocular toxicity, such as psoralen, risedronate, or tamoxifen;
• 6. Known allergy to the drug planned for use in the study；
• 7.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;
• 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. Any other conditions which leads the investigator to determine the participant is unsuitable for this study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking University Third Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Liping Yang, MD

Role: PRINCIPAL_INVESTIGATOR

Peking University Third Hospital

Locations

Peking University Third Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Liping Yang, MD

Role: CONTACT

alexlipingyang@bjmu.edu.cn

010-82266595

Jinlu Zhang, MD

Role: CONTACT

zhangjinlu@bjmu.edu.cn

15810570898

Facility Contacts

Jinlu Zhang, MD

Role: primary

zhangjinlu@bjmu.edu.cn

15810570898

Bingqian Cong, Bachelor

Role: backup

congbingqian@chinagene.cc

18500191916

Other Identifiers

ZYB-2022-001

Identifier Type: -

Identifier Source: org_study_id