Gaucher disease
Conditions
Interventions
Phase I: Experimental,LY-M001 Dose group 1:Participants receive a single, peripheral intravenous (IV) infusion of LY-M001 at dose group 1.
Phase I: Experimental,LY-M001 Dose group 2:Participants receive a single, peripheral intravenous (IV) infusion of LY-M001 at dose group 2.
Phase I: Experimental,LY-M001 Backdose:Participants receive a single, peripheral intravenous (IV) infusion of LY-M001 at backdose.
Phase II: Experimental,LY-M001 at the recommended dose:Participants receive a single, peripheral IV infusion of LY-M001 at the recommended dose.
Sponsors
Hematology Hospital, Chinese Academy of Medical Sciences
Eligibility
Sex/Gender
All
Age
18 Years to 60 Years
Inclusion criteria
Inclusion criteria: 1. Age: >=18 years and = 80 g/L but below the lower limit of normal; • Platelet count >= 40 × 10?/L but below the lower limit of normal; • Hepatomegaly; • Splenomegaly. Note: For treatment-naïve or untreated patients, the investigator must comprehensively assess and determine that the patient’s condition is stable and suitable for enrollment. Patients with severe systemic involvement should be enrolled with caution. 5. Negative pregnancy test for female subjects of childbearing potential (WOCBP); Notes:WOCBP is defined as female subjects who have experienced menarche but have not reached a postmenopausal state (at least 12 consecutive months of amenorrhea without other identified causes besides menopause), and have no surgical procedures (i.e., bilateral oophorectomy, salpingectomy, and/or hysterectomy) or other causes determined by the investigator (e.g., Müllerian agenesis) leading to permanent sterility. 6. Subjects and their partners have no childbearing plans from the screening period to 6 months after the end of the study, and voluntarily adopt effective contraceptive measures (e.g., abstinence, condoms, etc.); subjects have no plans to donate sperm or eggs. 7. Subjects are not to donate blood during the study and for at least 1 year after the end of the study.
Exclusion criteria
Exclusion criteria: 1. Positive for AAV8 neutralizing antibodies (antibody titer > 1:40). 2. Clinically suspected Type II or Type III Gaucher disease (GD2 or GD3) patients. 3. Active and progressive bone disease requiring surgical intervention within the next 6 months. 4. As judged by the investigator, the subject has idiopathic thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), thrombocytopenia, anemia, hepatomegaly, splenomegaly, and/or osteoporosis unrelated to GD. 5. Received treatment or intervention with investigational drugs or devices from other clinical studies within 28 days or 5 half-lives (whichever is longer) before screening. 6. Evidence of clinically significant liver disease, fragile liver, or exposure to liver toxins, meeting any of the following criteria at screening, but not limited to: • Progressive hepatomegaly greater than 3 times the normal volume. • History of liver fibrosis at stage 2 or above. • AST, ALT, or TBIL levels more than 1.5 times the upper limit of normal (ULN). • History of alcohol or drug abuse within the past 2 years (alcohol abuse defined as: weekly alcohol consumption greater than 14 standard units [1 standard unit contains 14 g of alcohol, equivalent to 360 mL of beer, 45 mL of liquor with 40% or higher alcohol content, or 150 mL of wine]). • Positive for hepatitis B surface antigen (HBsAg) and positive for hepatitis B virus deoxyribonucleic acid (HBV-DNA) (HBV-DNA > 10^3 copies/mL); or taking hepatitis B virus medications (such as interferon, lamivudine, adefovir, and entecavir); or positive for hepatitis C virus (HCV) antibody and positive for HCV RNA. 7. Positive for human immunodeficiency virus (HIV) antibody or positive for Treponema pallidum antibody. 8. Severe hyperlipidemia (triglycerides > 11.29 mmol/L). 9. Uncontrolled concomitant diseases or infectious diseases (requires judgment by the investigator based on clinical practice). 10. The subject has received or plans to receive bone marrow transplantation, hematopoietic stem cell transplantation, and/or major organ transplantation, including but not limited to liver transplantation, kidney transplantation, etc. 11. The subject has received erythropoietin, whole blood transfusion, or red blood cell transfusion within 3 months before screening; or received platelet transfusion within 1 month before screening. 12. Clinically diagnosed or judged by the investigator to have severe cardiovascular disease (such as New York Heart Association [NYHA] heart failure classification =3). 13. Allergic to any component of LY-M001 injection. 14. Previously received any type of gene therapy or cell therapy. 15. Used systemic immunosuppressants or steroid therapy within 3 months before administration (except for preventive immunosuppressive therapy as specified in the protocol). 16. History of cancer within 5 years before screening, except for completely resected non-melanoma skin cancer, non-metastatic prostate cancer, and completely cured ductal carcinoma in situ. 17. Received live attenuated vaccines within 4 months before screening or plans to receive live attenuated vaccines during the clinical trial. 18. Other conditions deemed by the investigator as unsuitable for the subject's participation in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase I: Incidence of dose-limiting toxicity (DLT) events as determined by the Data Safety Review Committee (SRC) at least 28 days after LY-M001 infusion;Phase I: Incidence of adverse events (AE) and serious adverse events (SAE) within 52 weeks of LY-M001 infusion;Phase I: Liver function (including alanine aminotransferase [ALT], aspartate aminotransferase [AST], total bilirubin [TBIL], alkaline phosphatase [ALP], and glutamyltransferase [GGT]) levels at 52 weeks post LY-M001 infusion;Phase II: Blood glucocerebrosidase (GCase) activity level;Phase II: The incidence of adverse events (AEs) and serious adverse events (SAEs), as well as the occurrence of abnormalities in 12-lead electrocardiogram (ECG) findings, vital signs, laboratory test parameters and physical examination results; | — |
Secondary
| Measure | Time frame |
|---|---|
| Phase I: Blood glucocerebrosidase (GCase) protein level and activity level;Phase I: Blood glucosylsphingosine (Lyso-GL1) levels;Phase I: Liver volume and spleen volume (if applicable);Phase I: Hemoglobin level and platelet count;Phase I: The occurrence of abnormalities in 12-lead electrocardiogram (ECG), vital signs, other laboratory test parameters, and physical examination findings.;Phase I: Bone mineral density (BMD) and bone marrow burden (BMB) after drug administration;Phase I: Score of quality of life scale for patients with GD;Phase I: GD Patient Fatigue Scale Score;Phase I: Distribution and shedding of Adeno-associated virus (AAV) 8 in blood, saliva, urine, and feces;Phase I: Production of ADA and NAb (when ADA is positive, corresponding NAb testing is performed) for AAV8, as well as GCase ADA in blood;Phase I: Cellular immunogenicity test: ELISPOT detection of IFN-? specific response levels in PBMC;Phase II: Blood GCase protein level;Phase II: Blood Lyso-GL1 level;Phase II: Liver volume and spleen volume (if applicable);Phase II: Hemoglobin level and platelet count;Phase II: BMD (Bone Mineral Density) and BMB (Bone Marrow Burden);Phase II: Quality of life scale score for patients with Gaucher Disease (GD);Phase II: Fatigue Scale score for patients with Gaucher Disease (GD);Phase II: Distribution and shedding of AAV8 virus in blood, saliva, urine, and feces;Phase II: Production of ADA and NAb (performing corresponding NAb testing when ADA is positive) for AAV8, as well as GCase ADA in blood;Phase II: Cellular immunogenicity test: ELISPOT detection of IFN-? specific response levels in PBMCs (Peripheral Blood Mononuclear Cells); | — |
Countries
China
Contacts
Public ContactFengkui Zhang
Hematology Hospital, Chinese Academy of Medical Sciences
Outcome results
None listed