Evaluating PUMCH-E101 Injection for RDH12 Retinopathy

An Open-Label, Single-Center, Dose-Escalation Clinical Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of Intravitreal Injection of PUMCH-E101 in Subjects with RDH12 Retinopathy

This study is testing a new gene therapy injection called PUMCH-E101 to see if it can help people with RDH12 retinopathy improve their vision and overall eye health.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 8 Years to 45 Years
• Sex: All
• Sponsor: Peking Union Medical College Hospital (Academic / other)
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT06749639 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to assess the safety and efficacy of PUMCH-E101, a gene therapy injection, in patients diagnosed with RDH12 retinopathy, an inherited retinal disease. It is an open-label, single-center, dose-escalation study where participants will receive a single intravitreal injection in one eye. Following the injection, participants will be monitored for 52 weeks, with continued follow-up for up to five years to evaluate long-term effects and outcomes.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 8 to 45 with a clinical diagnosis of inherited retinal disease caused by RDH12 mutations and specific visual acuity criteria.

Not a fit: Patients with significant ocular conditions that interfere with visual acuity detection or assessment will not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve vision and quality of life for patients with RDH12 retinopathy.

How similar studies have performed: While gene therapy for inherited retinal diseases is a growing field, this specific approach with PUMCH-E101 is novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

1. Subjects voluntarily participate and sign the informed consent form;
2. Age between 8-45 years old, gender is not limited;
3. Clinical diagnosis of IRD caused by RDH12 mutations;
4. The Best Corrected Visual Acuity (BCVA) detected by the Early Treatment Diabetic Retinopathy Study (ETDRS) eye chart in the study eye is less than or equal to 63 letters, which is equivalent to 20/63 of the Snellen Eye Chart;
5. At screening, the blood pregnancy test result of females of childbearing potential (e.g., females who have not undergone surgical sterilization or less than 1 year after menopause) is negative. Male and female subjects of childbearing potential agree to use effective contraception throughout the study and for at least 12 months after dosing.

Exclusion Criteria:

1. Opacity of refractive media or inability to dilate pupils in the study eye that significantly interferes with visual acuity detection, anterior segment or fundus assessment;
2. Presence of diabetic retinopathy, retinal vein occlusion, pathological myopia, retinal detachment, or other conditions in the study eye that are assessed by the investigator as affecting the safety of the subject or the validity of the study;
3. Any intraocular surgery in the study eye within 3 months prior to screening;
4. Active intraocular or periocular infection (such as blepharitis, conjunctivitis, keratitis, scleritis, etc.) in the study eye;
5. History of uveitis in either eye；
6. Those with diffuse intravascular coagulation and obvious bleeding tendency (such as hemoptysis, hematemesis, severe purpura, etc.) within 3 months before screening;
7. History of myocardial infarction, unstable angina, coronary revascularization, cerebrovascular accident (including TIA), history of other thromboembolic diseases (such as thromboembolic angiitis, pulmonary embolism, deep vein thrombosis, portal vein thrombosis, etc.), New York Heart Association (NYHA) grade ≥ II cardiac insufficiency, severe unstable ventricular arrhythmia, within 6 months prior to screening;
8. Subjects with systemic immune diseases (including systemic lupus erythematosus, ankylosing spondylitis, rheumatoid arthritis, etc.);
9. Diabetic patients with any of the following conditions: Known macrovascular complications or Glycosylated hemoglobin at screening（HbA1c）\>7.5% or Those who have received more than two oral hypoglycemic drugs or received insulin or GLP-1 receptor agonists therapies;
10. Hypertensive patients with poor blood pressure control (defined as: systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥100 mmHg when the subject is seated after receiving antihypertensive medication);
11. Any uncontrollable clinical illness (such as severe psychiatric, respiratory and other systemic diseases and history of malignant tumors);
12. Subjects 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 and urea/urea nitrogen ≥ 1.5 times the upper limit of normal;
13. Subjects with abnormal coagulation function: prothrombin time (PT) \> upper limit of normal value of 3 seconds or activated partial thromboplasting time (APTT) \> upper limit of normal value of 10 seconds; Haemoglobin (HGb) \< 10 g/dL;
14. Those who are positive for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, treponema pallidum antibody and human immunodeficiency virus (HIV) antibody;
15. Those who are known to be allergic to the therapeutic drugs or diagnostic drugs used in the study protocol, including the investigational products, etc.;
16. Those who have used anticoagulant or antiplatelet drugs within 7 days before dosing;
17. Currently using or may need to use drugs that can cause crystalline toxicity or retinal toxicity (such as deferoxamine, chloroquine/hydroxychloroquine, tamoxifen, ethambutol, etc.);
18. Those who have a history of surgical operation within 1 month before screening, and/or currently have unhealed wounds (wound degree\> stage III), moderate to severe ulcers, and fractures;
19. Subjects with systemic infectious diseases requiring systemic treatment (oral, intramuscular or intravenous) at the time of screening;
20. Those who have received any AAV gene therapy products in the past;
21. Pregnant or lactating females;
22. Those who have participated in any clinical trial of drugs (excluding vitamins and minerals) within 3 months before screening;
23. Other individuals who need to be excluded, as determined by the investigator

Where this trial is running

Beijing, Beijing Municipality

• Peking Union Medical College Hospital — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Principal investigator: Ruifang Sui, MD, PhD — Peking Union Medical College Hospital, Department of Ophthalmology
• Study coordinator: Ruifang Sui, MD, PhD

Conditions Inherited Retinal Diseases; Gene Therapy; Inherited Retinal Disease; RDH12 Mutations