Evaluation of the Safety, Tolerability and Efficacy of Gene Therapy Drug for Late Onset Pompe Disease (LOPD)

A Single-arm, Open-label, Single-dose Study to Evaluate the Safety, Tolerability, and Efficacy of CRG003 Injection in the Treatment of Late Onset Pompe Disease

This is a single-center, single-arm, open-label, single-dose treatment clinical study to evaluate the safety, tolerability and efficacy of CRG003 injection in participants with late onset Pompe disease (LOPD), with a long-term follow-up period of 5 years.

CRG003 (BBM-G102) injection is an adeno-associated virus (AAV) gene therapy product for treating Pompe disease to stably express active GAA enzyme in the liver on a long-term basis after the injection.

Inclusion Criteria:

1. Participants voluntarily sign informed consent form;
2. Clinically diagnosed with LOPD;
3. Males or females aged ≥ 18 years;
4. Undergone enzyme replacement treatment (ERT) with recombinant human acid alpha-glucosidase (rhGAA) previously, and has been discontinued for at least four weeks before screening;
5. Acceptable Pulmonary test results;
6. A 6MWT ≥ 100 meters, and ambulation for 40 meters without stopping and without an assistive device;
7. Acceptable laboratory values;
8. Acceptable GAA anti-drug antibody titer;
9. Acceptable capsid antibody titers;
10. Use of reliable contraception methods during the study;
11. Participants with good compliance.

Exclusion Criteria:

1. Severe cardiomyopathy was defined as left ventricular ejection fraction (LVEF) < 45% or New York Heart Association (NYHA) functional class 3 or above;
2. Require invasive mechanical ventilation, or rely on noninvasive ventilation during the day;
3. Intolerance to ERT, prior experience of serious infusion-associated reactions (IARs), prior experience of serious allergic reactions or investigator-assessed intolerance to ERT;
4. Have received any systemic immunosuppressants (except inhalation or topical use) other than glucocorticoids or investigator-recommended immunosuppressants 30 days prior to screening, and known intolerance to immunosuppressants such as glucocorticoids;
5. Positive for hepatitis B surface antigen (HBsAg) or hepatitis B virus DNA (HBV-DNA), positive for hepatitis C virus RNA (HCV-RNA). Participants with a history of hepatitis B or C can be regarded as negative if both two samples collected at an interval of at least three months are tested negative for the above parameters; positive for human immunodeficiency virus (HIV) or positive serologic test for syphilis;
6. Currently on antiviral therapy for hepatitis B or C;
7. Have clinical organic diseases (except symptoms or diseases associated with Pompe disease), including active tuberculosis, cardiovascular and cerebrovascular diseases, hepatobiliary system, respiratory system, nervous system, urinary system, or endocrine system disorders (such as diabetes, etc.), or other serious complications, or other conditions that make the patients not eligible for the study according to the investigator;
8. Have underlying liver diseases, e.g., prior diagnosis of portal hypertension, splenomegaly, hepatic encephalopathy, severe fatty liver, cirrhosis or liver fibrosis ≥stage 3; or ultrasound-identified liver neoplasms or laboratory tests suggesting elevated alpha-fetoprotein, etc., which are considered by the investigator as clinically significant;
9. Have received gene therapy prior to screening or used other investigational drugs or drugs that affect this study as evaluated by the investigator within four weeks prior to screening or within 5 half lives of the investigational drug (whichever is longer);
10. Have received or will receive any herbal preparations (herbal supplements or traditional Chinese medicines derived from plants, minerals, or animals, other than topical medications) that may affect liver function or Chinese herbal medicines that may affect the study as judged by the investigator four weeks prior to study medication or during the study follow-up period;
11. Alcohol dependence or drug addiction, and inability to stop alcohol intake as ordered by the doctor during the study;
12. Have received any live vaccine two months predose or history of vaccination within 30 days prior to screening or planning to receive vaccination during the screening and the main study period;
13. Pregnant or lactating female participants;
14. Other conditions that make the participants not eligible for the study according to the investigator.