A Multicenter, Open, Single-arm, Single-dose, Dose-escalation, and Expanded Phase I/II Study Evaluating the Safety, Tolerability, and Efficacy of LY-M001 Injection in Adult Patients With Type I Gaucher Disease
Gaucher disease (GD) is caused by mutations in the GBA1 gene, which leads to a lack or reduction of GCase activity. The consequences of this deficiency are generally attributed to the accumulation of the GCase substrate, Glucosylceramide (GlcCer), in macrophages in the liver, spleen, kidney, bone, lung, and even the brain, inducing their transformation into Gaucher cells whose cell cytoplasm presenting a characteristic crumpled tissue paper appearance, leading to pathological changes in involved tissues and organs.LY-M001 Injection is an rAAV8 vector gene therapy product. It can specifically transduce the target organ liver after a single intravenous administration and express the GCase protein in liver cells for a long period of time.
• Age ≥ 18 years and ≤ 60 years, male or female.
• The subjects should fully understand the purpose, nature, and method of this study as well as possible adverse reactions, and sign the informed consent form (ICF) voluntarily.
• Patients with confirmed double mutations in the GBA1 allele through laboratory testing, and the glucocerebrosidase activity was reduced to less than 30% of the normal value(For example, the result of the dried blood spot (DBS) method is \< 1.19 μmol/L/h), and meeting the standard clinical diagnosis criteria for GD1.
• Patients who meet a) or b) below:
‣ Treated patients with Gaucher disease type I who had previously received enzyme replacement therapy (ERT) or substrate clearance therapy (SRT) with GD, were on stable medication, eluted 5 drugs for a half-life or more before administration, or were comprehensively judged to be stable by the investigator.
⁃ Newly treated or untreated GD1 patients who meet one or more of the following criteria at screening:
• Hemoglobin ≥80g/L and less than the lower limit of normal;
∙ Platelets ≥40×10\^9/L and less than the lower limit of normal;
∙ Hepatomegaly;
∙ Splenomegaly.
• Negative pregnancy test for female subjects of childbearing potential (WOCBP). Notes: WOCBP is defined as the absence of postmenopausal status (continuous amenorrhea of at least 12 months with no identifiable cause other than menopause), and the absence of surgical (i.e., ovarian, salpingectomy, and/or hysterectomy) or Investigator-determined cause of permanent infertility due to other causes (e.g., lenticular hypoplasia) after menarche in female subjects.
• 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.
• Subjects are not to donate blood during the study and for at least 1 year after the end of the study.