Evaluating the safety and effectiveness of EXG110 for Fabry disease

A Multicenter, Non-randomized, Open-label, Dose-finding Study to Evaluate the Safety and Preliminary Efficacy of Gene Therapy With EXG110 in Subjects With Fabry Disease

This study is testing a new drug called EXG110 to see if it's safe and effective for people with Fabry disease, including both adults and kids aged 7 and up.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 7 Years and up
• Sex: All
• Sponsor: The Children's Hospital of Zhejiang University School of Medicine (Academic / other)
• Locations: 2 sites (Shanghai, Shanghai Municipality and 1 other locations)
• Trial ID: NCT06539624 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to assess the safety and tolerability of various doses of EXG110 in patients diagnosed with Fabry disease. It employs an open-label, multicenter, single-arm, non-randomized, dose-escalation design to evaluate the effects of a single intravenous administration of the drug. Participants will be monitored for clinical symptoms and any adverse reactions following treatment. The study includes both adults and children aged 7 and older who exhibit symptoms of Fabry disease.

Who should consider this trial

Good fit: Ideal candidates for this study are individuals aged 7 and older with a confirmed genetic diagnosis of Fabry disease and at least one related clinical symptom.

Not a fit: Patients without Fabry disease or those who do not exhibit any symptoms related to the condition may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients suffering from Fabry disease.

How similar studies have performed: While there have been studies on treatments for Fabry disease, the specific approach of using EXG110 is novel and has not been extensively tested in prior trials.

Eligibility criteria

Inclusion Criteria:

1. At the time of signing the informed consent, age ≥7, 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 (adults only)
5. All subjects of reproductive age voluntarily took effective contraception and prohibited sperm donation from entering the screening period until 52 weeks after dosing (main study period)
6. The subjects voluntarily participate and are fully informed, fully understand the research, can comply with the requirements of the research protocol, and are willing to complete the research as planned, 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) Albumin \< lower limit of normal (LLN)
2. There was a clinically significant increase in AFP during the screening period
3. 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
4. AVT917 (\>1:50), anti-AGA antibody positive(\>1:2560)
5. C3 lower than the normal range, C5b-9 higher than the normal range, anti-AVT917 IgM positive
6. Current or have a history of serious cardiovascular disease and surgical history
7. Current underlying liver disease or history of liver disease, as assessed by the investigator, that may affect the safety assessment of the drug
8. Renal disease in adult and the slope of kidney \>5 mL/min/1.73m²/year
9. Subjects with poorly controlled diabetes after drug treatment (e.g., HbA1c≥8%);
10. Acute/chronic infection or other chronic disease that the investigator determines will increase the risk of participants participating in the study
11. Patients 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);
12. Have malignancy cancer
13. Patients with active autoimmune diseases (such as rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, immune vasculitis, inflammatory bowel disease, etc.);
14. known history of allergy to the components of the investigational products
15. Patients with a history of drug use or drug abuse or alcoholism
16. Use of systemic (intravenous or oral) immunomodulators within the past 6 months or currently
17. Initiation of treatment with blood pressure lowering drugs that affect proteinuria levels (such as angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, or angiotensin-receptor/enkephalin inhibitors) within 4 weeks prior to screening, or changes in the therapeutic dose of these drugs within 4 weeks prior to screening;
18. Has received, or is 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 (or within 5 half-lives of the investigational drug, whichever is longer)
19. Previous treatment with gene therapy products
20. Those who had received live attenuated vaccine/vaccine within 12 weeks prior to screening or planned to receive it during the study
21. Other clinical conditions that the investigators felt needed to be ruled out

Where this trial is running

Shanghai, Shanghai Municipality and 1 other locations

• Shanghai Children's Medical Center — Shanghai, Shanghai Municipality, China (Recruiting)
• Children's Hospital, Zhejiang University School of Medicine — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Principal investigator: Jianhua Mao, PhD — The Children's Hospital of Zhejiang University School of Medicine
• Study coordinator: Jianhua Mao, PhD

Conditions Fabry Disease