Safety and Efficacy Study of PUMCH-E101 Injection in Subjects with 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

The goal of this clinical trial is to evaluate the safety and efficacy of PUMCH-E101 injection in subjects with RDH12 retinopathy.

Study Overview

• Status: Recruiting
• Conditions: Inherited Retinal Diseases
• Intervention / Treatment: Genetic: PUMCH-E101 Injection（Low dose）; Genetic: PUMCH-E101 Injection（High dose）

Detailed Description

This is an open-label, single-center, dose-escalation study. One eye of each participant will receive a single intravitreal injection of PUMCH-E101. Participants will be followed for 52 weeks after which they will continue to be followed for up to 5 years after enrollment.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Ruifang Sui, MD, PhD; Phone Number: +8613511017280; Email: Hrfsui@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Recruiting
      • Peking Union Medical College Hospital
      • Contact: Ruifang Sui, MD, PhD; Phone Number: +8613511017280; Email: Hrfsui@163.com
      • Contact: Ruifang Sui, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PUMCH-E101 Treatment Arm（Low dose）; Intraocular injection of a single low dose of PUMCH-E101	Genetic: PUMCH-E101 Injection（Low dose）; Single intravitreal injection
Experimental: PUMCH-E101 Treatment Arm（High dose）; Intraocular injection of a single high dose of PUMCH-E101	Genetic: PUMCH-E101 Injection（High dose）; Single intravitreal injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of AEs	Number and severity of overall and ocular Adverse Events (AEs)	52 weeks
Incidence of SAEs	Number and severity of overall and ocular Serious Adverse Events (SAEs)	52 weeks
Incidence of DLTs	Number and proportion of dose limited toxicity (DLTs)	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual function	Change from baseline in BCVA (Best Corrected Visual Acuity) (ETDRS)	52 weeks
Visual function	Change from baseline in the mean value of the photosensitivity threshold (Full-field Threshold)	52 weeks
Visual function	Change from baseline in mean sensitivity (MS) (Static visual field)	52 weeks

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Investigators: Principal Investigator: Ruifang Sui, MD, PhD, Peking Union Medical College Hospital, Department of Ophthalmology

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): January 4, 2030

Study Registration Dates

• First Submitted: December 19, 2024
• First Submitted That Met QC Criteria: December 24, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 29, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Gene Therapy; Inherited Retinal Disease; RDH12 Mutations
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Diseases
• Other Study ID Numbers: PUMCH-E101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No