A Clinical Study Evaluating LY-M001 Injection in the Treatment of Adult Patients With Type I Gaucher Disease

NCT06818838 | Recruiting Phase 1

• 1 other identifier: LY-M001-GD-101
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Gaucher Disease Type 1

Keywords

anaemia; Gene therapy

Outcome Measures

Primary Outcomes (5)

• Phase I: Incidence of adverse events (AE) and serious adverse events (SAE) within 52 weeks after LY-M001 infusion

  Number of participants with treatment-related adverse events as assessed by CTCAE v5.0.

  From enrollment to 52 weeks after administration

• Phase I: Incidence rate of dose-limiting toxicity (DLT) events determined by the data safety review committee (SRC) within at least 28 days after LY-M001 infusion.

  Number of participants with treatment-related adverse events as assessed by CTCAE v5.0.The adverse events defined as dose-limiting toxicity (DLT) have been clearly specified in the protocol.

  From enrollment to 52 weeks after administration

• Phase I: Liver function levels (including alanine aminotransferase [ALT], aspartate aminotransferase [AST], total bilirubin [TBIL], alkaline phosphatase [ALP], gamma-glutamyl transferase [GGT]) within 52 weeks after LY-M001 infusion.

  Incidence rate of liver function-related adverse events evaluated by CTCAE V5.0.

  From enrollment to 52 weeks after administration

• Phase II: Blood glucocerebrosidase (GCase) activity level.

  Evaluation based on the detected values of blood glucocerebrosidase（GCase).

  From enrollment to 52 weeks after administration

• Phase II: The incidence rates 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.

  Number of participants with treatment-related adverse events as assessed by CTCAE v5.0.

  From enrollment to 52 weeks after administration

Secondary Outcomes (15)

• Phase I: Liver volume and spleen volume (if applicable)

  From enrollment to 52 weeks after administration

• Phase I: Hemoglobin levels

  From enrollment to 52 weeks after administration

• Phase I:Bone mineral density (BMD) after administration

  From enrollment to 52 weeks after administration

• Phase I: Glucocerebrosidase (GCase) protein levels in blood

  From enrollment to 52 weeks after administration

• Phase I: Glucosylsphingosine (Lyso-GL1) in blood

  From enrollment to 52 weeks after administration

Study Arms (4)

Phase I: LY-M001 Backdose

EXPERIMENTAL

Participants receive a single, peripheral intravenous (IV) infusion of LY-M001 at backdose.

Genetic: LY-M001

Phase I: LY-M001 Dose group 1

EXPERIMENTAL

Participants receive a single, peripheral intravenous (IV) infusion of LY-M001 at dose group 1.

Genetic: LY-M001

Phase I: LY-M001 Dose group 2

EXPERIMENTAL

Participants receive a single, peripheral intravenous (IV) infusion of LY-M001 at dose group 2.

Genetic: LY-M001

Phase II: LY-M001 at the recommended dose

EXPERIMENTAL

Participants receive a single, peripheral IV infusion of LY-M001 at the recommended dose.

Genetic: LY-M001

Interventions

LY-M001 GENETIC

Single Intravenous Infusion of LY-M001 Injection.

Phase I: LY-M001 Backdose; Phase I: LY-M001 Dose group 1; Phase I: LY-M001 Dose group 2; Phase II: LY-M001 at the recommended dose

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• AAV8 neutralizing antibody positive (Antibody titer \> 1:40).
• Patients with clinically diagnosed Gaucher disease type II or III (GD2 or GD3).
• Active and progressive bone disease that is expected to require surgical treatment within the next 6 months.
• Subject has idiopathic thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), thrombocytopenia, anemia, hepatomegaly, splenomegaly, and/or osteoporosis unrelated to GD as judged by the Investigator.
• Treatment or disposal of investigational drugs or investigational devices received in other clinical studies within 28 days prior to screening or within 5 half-lives (drugs only), whichever is older.
• Evidence of clinically significant liver disease, fragile liver, or history of exposure to hepatotoxins that meets, but is not limited to, any of the following at the time of screening:
• Progressive hepatomegaly larger than 3 times the normal volume.
• History of stage 2 or above liver fibrosis.
• AST, ALT, or TBIL are 1.5 times higher than ULN.
• A history of alcohol or drug abuse within the previous 2 years (defined as having consumed more than 14 standard units of alcohol per week \[1 standard unit containing 14 g of alcohol, such as 360 mL beer, 45 mL spirits containing 40% or more alcohol, or 150 mL wine\]).
• Hepatitis B surface antigen (HBsAg) positive and HBV deoxyribonucleic acid (HBV-DNA) positive (HBV-DNA\>10\^3 copy number /mL); Or take hepatitis B drugs (such as interferon, lamivudine, adefovir and entecavir); Or antibodies to hepatitis C virus (HCV) and positive for hepatitis C virus RNA.
• Human immunodeficiency virus (HIV) antibody positive or Treponema pallidum antibody positive.
• Severe hyperlipidemia (triglycerides \> 11.29mol/L).
• Uncontrolled concomitant or infectious diseases (need to be determined by the investigator based on clinical practice).
• 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.

Sponsors & Collaborators

• Lingyi Biotech Co., Ltd.: lead

Study Sites (3)

Guangzhou First People's Hospital

Guangzhou, Guangdong, 510000, China

RECRUITING

Shanxi Bethune Hospital

Taiyuan, Shanxi, 030000, China

RECRUITING

Hematology Hospital, Chinese Academy of Medical Sciences

Tianjin, Tianjin Municipality, 300011, China

RECRUITING

MeSH Terms

Conditions

Gaucher Disease; Anemia

Condition Hierarchy (Ancestors)

Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Fengkui Zhang, PhD

  Hematology Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Qing Lin, PhD

CONTACT

86+19121572057; qing.lin@lingyimed.com

Yixiong Chen, PhD

CONTACT

86+19121572057; yixiong.chen@lingyimed.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2025
• First Posted: February 11, 2025
• Study Start: July 5, 2024
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): July 30, 2031
• Last Updated: January 26, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)