safety and efficacy study of novel gene therapy zm-02 for retinitis pigmentosa patients

Conditions: Retinitis Pigmentosa

Summary: this is zm-02's safety, tolerability, and efficacy in retinitis pigmentosa first-in-human study (moon). this trial is meant to evaluate the safety and efficacy of zm-02 in retinitis pigmentosa (rp) patients. unilateral intravitreal injections (ivt) will be given into the subject's study eye.

retinitis pigmentosa (rp) is the most common inherited retinal disease. individuals affected by rp often experience progressive visual impairment, potentially leading to legal blindness. there is currently no established effective clinical treatment available. we developed an innovative adeno-associated virus (aav)-based gene therapy for individuals with rp, regardless of their causative mutations. eight to twelve subjects with rp will be recruited and six to nine of them will receive a single unilateral intravitreal injection of zm-02 at ascending doses, while two to three receive sham injections as the control group.

Eligibility criteria:
inclusion criteria: patients who meet all of the following criteria can be selected as subjects: 1. clinically diagnosed with retinal pigment degeneration 2. the vision of the eye being tested is no better than the index value, while the vision of the opposite eye is not better than that of the tested eye 3. the subject has had visual experience above the index value 4. in the oct examination of the tested eye, the disappearance of the ellipsoid zone is observed, but the inner nuclear layer and the nerve fiber layer of the retina are still present 5. the refractive power of the tested eye is between -6.00 d and +6.00 d 6. not infected with the human immunodeficiency virus (hiv) and other acute and chronic infectious diseases 7. voluntarily sign an informed consent form (icf), and the age is not less than 18 years and not more than 65 years 8. able to fully understand and agree to cooperate with the implementation of the research protocol exclusion criteria: subjects who meet any one of the following exclusion criteria will be excluded from the study: 1. pregnant women, breastfeeding women, or male and female subjects who do not agree to contraception during the 12 months before and after medication 2. subjects with narrow anterior chamber angles or any other medical conditions that contraindicate pupil dilation 3. subjects allergic to corticosteroids, who are unable to tolerate the corticosteroid treatment described in the protocol, or have active 4. concurrent infections that contraindicate treatment 4. subjects with systemic diseases, or other medical or mental illnesses, or other safety concerns for the study 5. subjects with other symptoms and/or diseases or conditions that can alter visual function, including but not limited to glaucoma and central nervous system lesions (mild cataracts are not included in this restriction) 6. eye diseases that may interfere with the assessment of vision during the study and/or interfere with other ocular assessments such as oct 7. diseases that may affect the clinical trial, such as tumors, metabolic, immune-related diseases, etc. 8. subjects who have undergone major eye surgery within the last 3 months before screening 9. subjects with a history of malignant tumors within the last 5 years 10. subjects with other retinal diseases not suitable for this study, such as retinal detachment 11. patients undergoing or potentially undergoing immunosuppressive treatment for other diseases, excluding this study 12. participation in any clinical trials other than this study within the last 3 months 13. subjects who have received gene therapy outside of this study 14. other reasons deemed by the researcher as unsuitable for participation in this study

Keywords: gene therapy aav rp optogenetics