Pompe Disease (Late-onset) Clinical Trial
Official title:
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.
Status | Not yet recruiting |
Enrollment | 6 |
Est. completion date | December 2028 |
Est. primary completion date | December 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | 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. |
Country | Name | City | State |
---|---|---|---|
China | Huashan Hospital of Fudan University | Shanghai |
Lead Sponsor | Collaborator |
---|---|
Huashan Hospital |
China,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Incidence of dose limited toxicities | Incidence of dose limited toxicities (DLTs) as determined by the safety review committee (SRC) within 12 weeks following CRG003 infusion; | 12 weeks | |
Primary | Incidence of adverse events and serious adverse events | Incidence of adverse events (AEs) and serious adverse events (SAEs) within 26 weeks and 52 weeks following CRG003 infusion | 26 weeks and 52 weeks | |
Primary | The change of hepatic enzyme concentration | Alkaline phosphatase (ALP) | 26 weeks and 52 weeks | |
Primary | Changes from baseline in liver function | Changes from baseline in liver function [Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT) and total bilirubin (TBIL)] within 26 weeks and 52 weeks following CRG003 infusion | 26 weeks and 52 weeks |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT00158600 -
A Placebo-Controlled Study of Safety and Effectiveness of Myozyme (Alglucosidase Alfa) in Patients With Late-Onset Pompe Disease
|
Phase 3 | |
Recruiting |
NCT04174105 -
Gene Transfer Study in Patients With Late Onset Pompe Disease
|
Phase 1/Phase 2 | |
Active, not recruiting |
NCT04093349 -
A Gene Transfer Study for Late-Onset Pompe Disease (RESOLUTE)
|
Phase 1/Phase 2 | |
Completed |
NCT03285126 -
Pompe Gene Therapy- Screening for Eligibility
|
||
Recruiting |
NCT05083806 -
MSOT in Pompe Disease
|
N/A | |
Recruiting |
NCT05272969 -
Pompe & Pain - Study to Assess Nociceptive Pain in Adult Patients With Pompe Disease
|
||
Active, not recruiting |
NCT03694561 -
Developing a Management Approach for Patients With "Late-Onset" Pompe Disease
|
||
Completed |
NCT00731081 -
Study About the Evolution of Severe Late Onset Pompe Disease Patient With Pulmonary Dysfunction and Receiving Myozyme®
|
N/A | |
Completed |
NCT00455195 -
Late-Onset Treatment Study Extension Protocol
|
Phase 4 | |
Recruiting |
NCT05951790 -
Inspiratory Muscle Training (IMT) in Adult People With Pompe Disease
|
N/A | |
Completed |
NCT01288027 -
Exploratory Muscle Biopsy Assessment Study in Patients With Late-Onset Pompe Disease Treated With Alglucosidase Alfa
|
Phase 4 | |
Recruiting |
NCT00567073 -
Pompe Pregnancy Sub-Registry
|
||
Completed |
NCT03893240 -
Neutralizing Antibody Seroprevalence Study With a Retrospective Component in Participants With Late-Onset Pompe Disease
|
N/A | |
Withdrawn |
NCT04094948 -
Phase II Clinical Trial of Clenbuterol in Adult Patients With Pompe Disease
|
Phase 2 | |
Completed |
NCT00250939 -
A Study of rhGAA in Patients With Late-Onset Pompe Disease
|
Phase 2 | |
Recruiting |
NCT03911505 -
ZIP Study-OL Study of Safety, PK, Efficacy, PD, Immunogenicity of ATB200/AT2221 in Pediatrics Aged 0 to < 18 y.o. w/LOPD
|
Phase 3 | |
Recruiting |
NCT06150820 -
A Study About Antibody Levels and Biomarkers in the Blood in People With Late-onset Pompe Disease
|
N/A | |
Completed |
NCT03729362 -
A Study Comparing ATB200/AT2221 With Alglucosidase Alfa/Placebo in Adult Subjects With Late-onset Pompe Disease
|
Phase 3 | |
Completed |
NCT00268944 -
Safety and Effectiveness Study of rhGAA in Patients With Advanced Late-Onset Pompe Disease Receiving Respiratory Support
|
Phase 3 | |
Active, not recruiting |
NCT04138277 -
A Study to Assess the Long-term Safety and Efficacy of ATB200/AT2221 in Adult Subjects With LOPD
|
Phase 3 |