The Safety and Efficacy of Intravenous EXG110 in Patients With Fabry Disease

A Phase 1/2, Multicenter, Open-label,Dose-escalation Study to Evaluate the Safety and Efficacy of Intravenous EXG110 in Patients With Fabry Disease

A phase 1/2, multicenter, open-label, Dose-escalation study to evaluate the safety and efficacy of intravenous EXG110 in patients with Fabry disease

Study Overview

• Status: Not yet recruiting
• Conditions: Fabry Disease
• Intervention / Treatment: Drug: EXG110 Injection

Detailed Description

Phase 1: Dose -escalation，2 Groups Phase 2: Dose- expansion，1 Group

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Zhihong Liu, MD; Phone Number: +86 137 0158 9469; Email: chenpl166@163.com

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China
      • General Hospital of Eastern Theater Command
      • Principal Investigator: Zhihong Liu, MD
      • Contact: Peiling Chen, MD; Phone Number: +86 137 0158 9469; Email: chenpl166@163.com
      • Sub-Investigator: Zhen Cheng, PhD
      • Sub-Investigator: Yuanmao Tu, MD
      • Sub-Investigator: Dandan Qiu, MD
      • Sub-Investigator: Peiling Chen, MD
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • First Affiliated Hospital of Zhejiang University
      • Contact: Xiaogang Guo, PhD; Phone Number: +86 13867741856; Email: michelleyan2000@126.com
      • Principal Investigator: Xiaogang Guo, PhD
      • Sub-Investigator: Hui Yan, PhD
      • Sub-Investigator: Pei Zhou, PhD
    • Hangzhou, Zhejiang, China
      • Children's Hospital ZheJiang University School of Medicine
      • Principal Investigator: Jianhua Mao, PhD
      • Contact: Jianhua Mao, PhD; Phone Number: +86 13616819071; Email: maojh88@zju.edu.cn
      • Sub-Investigator: Zhihong Liu, PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥18 years old, male or female
2. Clinical symptoms (at least one Fabry disease related symptom) and genetic diagnosis of Fabry disease
3. Prior or no prior ERT treatment
4. Have renal or cardiac involvement
5. The participant voluntarily participate and are fully informed, fully understood the study, can comply with the requirements of the protocol, and voluntarily provide biological samples for testing according to the requirements of the protocol

Exclusion Criteria:

1. Screening period laboratory test results: a) aspartate aminotransferase or alanine aminotransferase > 1.5× upper limit of normal (ULN);b) Total bilirubin > 1.5× upper limit of normal (ULN);c) Alkaline phosphatase > 2× upper limit of normal (ULN);d) Hypoalbuminemia ≥ grade 2
2. Serum virology test: a) Hepatitis B: Hepatitis B virus surface antigen (HBsAg) positive, and hepatitis B virus-deoxyribonucleic acid (HBV-DNA) higher than the upper limit of normal detection;b) Hepatitis C: if the hepatitis C virus (HCV) antibody is positive, and the hepatitis C virus-ribonucleic acid (HCV-RNA) is higher than the upper limit of normal test value;c) Syphilis: positive for syphilis screening (Tp-Ab) and positive for syphile-specific antibodies;d) HIV: Known human immunodeficiency virus (HIV) positive history or HIV screening positive
3. Current or have a history of serious cardiovascular disease and surgical history
4. Current underlying liver disease or history of liver disease, as assessed by the investigator, that may affect the safety assessment of the product
5. Acute/chronic infection or other chronic disease that the investigator evaluated will increase the risk of participants in the study
6. Those who have a history of epilepsy, mental illness (such as schizophrenia, depression, mania or anxiety, etc.) or obvious mental disorders, and are incapacitated or cognitively incapacitated due to other reasons.
7. Participant with a history of malignant tumor or currently suffering from any malignant tumor (except for the following tumor diseases: skin basal cell carcinoma, cervical carcinoma in situ, breast carcinoma in situ , skin squamous cell carcinoma has been controlled after treatment);
8. Participant with active autoimmune diseases (such as rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, immune vasculitis, inflammatory bowel disease, etc.);
9. known history of allergy to the components of the investigational products
10. Participant with a history of drug use or drug abuse or alcoholism
11. Has received, or currently receiving, a clinical trial of another investigational drug/medical device or treatment (other than vitamins and minerals) within 3 months prior to signing the informed consent form (or within 5 half-lives of the investigational drug, whichever is longer)
12. Previous treatment with gene therapy products
13. Those who had received live attenuated vaccine/vaccine within 12 weeks prior to screening or planned to receive it during the study
14. Other clinical conditions that the investigators evaluated needed to be excluded

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: Low dose arm; EXG110 injection, use once by intravenous	Drug: EXG110 Injection; EXG110 Injection is gene therapy for Fabry Disease , uses a proprietary AAV capsid with improved liver and muscle specificity.
Experimental: High dose arm; EXG110 injection, use once by intravenous	Drug: EXG110 Injection; EXG110 Injection is gene therapy for Fabry Disease , uses a proprietary AAV capsid with improved liver and muscle specificity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: To evaluate the safety and tolerability of EXG110 following a single intravenous infusion	Adverse events (AEs), serious adverse events (SAEs), dose-limited toxicity types, severity, incidence,	52 weeks
Phase 2: The changes from the baseline of kidney function	Proportion of participants with a reduction in Gb3 inclusion body accumulation to scores 0 (the minimum values are 0 scores, the maximum values are 3, higher scores mean a worse outcome ) on renal interstitial capillary biopsy as determined by light microscopy.	6 months
Phase 2: The changes from the baseline of cardiac function	The change of LVMI (left ventricular mass index，g/m^2) from the baseline	6 months
Phase 2: The changes from the baseline of pain	The scores changes of BPI (The Brief Pain Inventory, short form) from the baseline, each iteam is scored on a 0-10 scale, with higher scores indicating greater severity.	6 months
Phase 2: The changes from the baseline of gastrointestinal function	The scores changes of GSRS (Gastrointestinal Symptom Rating Scale) from the baseline the minimum values are 0 scores, the maximum values are 35, higher scores mean a worse outcome	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
eGFR	eGFR change from baseline in mL/min/(1.73m^2)	52 weeks
Cardiac function	LVMI change from baseline	52 weeks

Collaborators and Investigators

• Sponsor: Hangzhou Jiayin Biotech Ltd
• Investigators: Principal Investigator: Zhihong Liu, MD, The General Hospital of Eastern Theater Command

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2025
• Primary Completion (Estimated): March 15, 2028
• Study Completion (Estimated): March 15, 2028

Study Registration Dates

• First Submitted: January 22, 2025
• First Submitted That Met QC Criteria: February 10, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 10, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Lipid Metabolism Disorders; Genetic Diseases, X-Linked; Lysosomal Storage Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases, Nervous System; Cerebral Small Vessel Diseases; Sphingolipidoses; Lipidoses; Fabry Disease
• Other Study ID Numbers: EXG110-111

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All data will be generated in this study are the property of Hangzhou Jiayin and should be kept strictly confidential together with the information provided by Hangzhou Jiayin. Investigator or any other delegated staff are not permitted to independently analyze and/or publish these data without the prior written authorization of Hangzhou Jiain.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No