RDH12-associated inherited retinal diseases
Conditions
Interventions
High-dose group:High dose of PUMCH-E101 Injcetion
Sponsors
Chinese Academy of Medical Sciences, Peking Union Medical College Hospital
Eligibility
Sex/Gender
All
Age
8 Years to 45 Years
Inclusion criteria
Inclusion criteria: 1.Patients who had undergone treatment for one eye within the PUMCH-E101 protocol and had completed a one-year follow-up period; 2.The participant is willing to participate voluntarily and sign an informed consent form, and is willing and able to adhere to the visit schedule, treatment plan, undergo laboratory tests, and comply with other study procedures; 3.Male or female between the ages of 8 and 45; 4.The study eye’s best corrected visual acuity (BCVA) measured using the ETDRS (Early Treatment Diabetic Retinopathy Study) visual acuity chart is not higher than 78 letters (including the boundary value), equivalent to not higher than 20/32 on the Snellen visual acuity chart; 5.During the screening process, the blood pregnancy test results were negative for women of childbearing age (e.g., those who have not undergone surgical sterilization or are postmenopausal for less than 1 year). Both male and female participants of childbearing age and their partners agreed to use effective contraceptive measures throughout the study period and for at least 12 months following the administration of the medication.
Exclusion criteria
Exclusion criteria: 1.There are significant factors that interfere with visual acuity testing, assessment of the anterior segment, or evaluation of the retina: opacities in the refractive medium or inability of the pupil to dilate; 2.The study involves participants with conditions such as diabetic retinopathy, retinal vein occlusion, pathological myopia, and retinal detachment. The researchers assess whether these conditions pose a risk to the participant’s safety or compromise the validity of the study; 3.Study the presence of active intraocular or periocular infections in the eyes (e.g., blepharitis, conjunctivitis, keratitis, scleritis, etc.); 4.The study eye had a history of vitreous hemorrhage within the previous 6 months prior to screening; 5.The eye has undergone an intraocular procedure within the previous 3 months prior to screening (e.g., cataract surgery, vitrectomy, small-trabecular meshwork removal, or other filtering surgeries); 6.Any eye with a history of glaucoma; 7.Any eye with a history of uveitis; 8. Individuals with disseminated intravascular coagulation and a clear bleeding tendency within the previous 3 months (e.g., hemoptysis, hematemesis, severe purpura) prior to screening; 9.History of myocardial infarction, unstable angina pectoris, coronary revascularization procedures within the previous 6 months, history of cerebrovascular accidents (including TIAs), other thromboembolic diseases (such as thromboembolic vasculitis, pulmonary embolism, deep vein thrombosis, portal vein thrombosis), New York Heart Association (NYHA) class = II heart failure, severe unstable ventricular arrhythmias; 10. Individuals with systemic immune disorders (including systemic lupus erythematosus, ankylosing spondylitis, rheumatoid arthritis, and others); 11.Diabetic patients who meet any of the following criteria: (1) known presence of major vascular complications; (2) HbA1c >= 7.5% during screening; (3) treatment with more than one oral hypoglycemic agent or insulin or GLP-1 receptor agonist; 12. Individuals with uncontrolled hypertension (defined as having a systolic blood pressure >= 160 mmHg or diastolic blood pressure >= 100 mmHg while seated after commencing antihypertensive medication); 13.Any uncontrolled clinical condition (such as severe mental, respiratory, or other systemic diseases, as well as a history of malignant tumors); 14. Individuals with abnormal liver and kidney function: alanine aminotransferase (ALT)/aspartate aminotransferase (AST) >= 2 times the upper limit of normal; total bilirubin >= 1.5 times the upper limit of normal; creatinine, urea/uric acid >= 1.5 times upper limit of normal; 15.Individuals with abnormal coagulation function: Prothrombin time (PT) > the upper limit of normal value by 3 seconds or Activated Partial Thromboplastin Time (APTT) > the upper limit of normal by 10 seconds; Hemoglobin (Hb) < 10 g/dL; 16. Individuals with positive results for hepatitis B surface antigen (HBsAg), antibodies against hepatitis C virus (HCV), antibodies against syphilis spirochetes, and antibodies against human immunodeficiency virus (HIV); 17. Individuals known to be allergic to the treatment or diagnostic medications used in the study protocol, including the study drugs; 18.Individuals who have used anticoagulant or antiplatelet medications within the 7 days preceding administration; 19.Currently taking or may need to take medications that could cause crystal toxicity or retinal toxicity (e.g., deferoxamine, chloroquine/hydroxychloro
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The incidence of DLT;AE/SAE; | — |
Secondary
| Measure | Time frame |
|---|---|
| Changes in best corrected visual acuity (BCVA) compared to the baseline;Viral shedding: the copy number of the vector genome DNA in peripheral blood and tear fluid.;Change in low-light visual acuity (LLVA) compared to baseline;Changes in the average sensitivity (MS) of static visual acuity compared to baseline;Immunogenicity: Changes in the titers of anti-AAV antibodies, anti-AAV neutralizing antibodies; variations in IFN-? levels against AAV and RDH12 compared to baseline.;Changes in scores from the Visual Function Questionnaire-25 (NEI VFQ-25) administered by the National Eye Institute and the Michigan Retinal Degeneration Questionnaire (MRDQ) and its pediatric version;Changes in the concentration of 4-hydroxynonenal (4-HNE) in the urine compared to the baseline value; | — |
Countries
China
Contacts
Public ContactRuifang Sui
Chinese Academy of Medical Sciences, Peking Union Medical College Hospital
Outcome results
None listed