A Study of the Safety and Preliminary Efficacy of LY-M001 Injection in the Treatment of Adult Patients with Gaucher Disease Type I

NCT06162338 | Recruiting

• 1 other identifier: LY-M001-GD-001
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective single-center, open, single-arm, single-dose intravenous infusion study to evaluate the safety and initial efficacy, pharmacodynamic characteristics, immunogenicity, biodistribution, and viral shedding of LY-M001 injection.This study mainly includes the main study stage and the long-term follow-up study stage.

Conditions

Gaucher Disease Type I

Outcome Measures

Primary Outcomes (2)

• Incidence of treatment- related adverse events

  Number and severity of adverse events and serious adverse events and relationship to LY-M001

  within 38 weeks after LY-M001 infusion

• Incidence of events adjudicated as dose limiting toxicity (DLT)

  Number and severity of dose limiting toxicity

  within 28 days after LY-M001 infusion

Secondary Outcomes (2)

• Glucocerebrosidase (GCase) protein in plasma and GCase enzyme activity

  Within 38 Weeks after LY-M001 infusion

• Glucosylsphingosine (Lyso-GL1)in plasma

  Within 38 Weeks after LY-M001 infusion

Study Arms (1)

A Prospective, single-center, open, single-arm study

EXPERIMENTAL

The study is single-arm. LY-M001 injection is administered by intravenous infusion at a rate of 1 mL per minute.LY-M001 Injection is Clear and colorless liquid.According to the dose cohort of the subject, the required dosage was accurately calculated by the patient's body weight for infusion.

Biological: LY-M001 Injection

Interventions

LY-M001 Injection BIOLOGICAL

With 5.0 × 10\^12 vg/kg as the initial effective dose (first dose group), 1 to 2 subjects are expected to be included. The first dose group was enrolled by sentinel method, and the first subject in this group was observed for at least 28 days after receiving LY-M001 (dose-limited toxicity \[DLT\] observation period) to enroll the next subject. After the first participant completes the safety evaluation of dosing for at least 28 days, the investigator (PI) and the partner discuss the safety and efficacy data and decide to maintain the first dose or increase/reduce it to another dose group

A Prospective, single-center, open, single-arm study

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 GD1 who have confirmed double mutations in the Gba1 allele by laboratory testing and meet the standard for clinical diagnosis of Gaucher disease (i.e., reduced GCase enzyme activity to less than 30% of normal values).
• The subjects were type I patients with Gaucher disease. Patients with type I Gaucher disease who had received specific treatment in the past required 5 half-lives of elution
• Negative pregnancy test for female subjects of childbearing potential 6.6.The subject and his/her partner have no plans to have children during the screening period and within 6 months after the end of the study, and voluntarily take effective contraceptive measures (such as abstinence, condom, etc.); and the subject had 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 is strongly positive.
• Patients with clinically suspected Gaucher disease type II (GD2) or Gaucher disease type III (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 Gaucher disease as judged by the investigator.
• Treatment or disposition of an investigational drug or investigational device for another clinical investigation within 28 days or 5 half-lives (only for drugs), whichever is longer, prior to Screening.
• Evidence of clinically significant liver disease, fragile liver, or history of hepatotoxin exposure, meeting at screening, but not limited to, any of the following:
• Progressive hepatomegaly and greater than 3 times normal volume.
• History of stage 2 or greater liver fibrosis.
• AST, ALT or TBIL greater than 1.5 times the upper limit of normal (ULN).
• History of alcohol or drug abuse within the previous 2 years.
• Hepatitis B surface antigen (HBsAg) positive, and hepatitis B virus DNA positive (HBV-DNA \> 103 copies/mL); or taking hepatitis B virus drugs (such as interferon, lamivudine, adefovir and entecavir); or hepatitis C virus (HCV) antibody positive.
• Human immunodeficiency virus (HIV) antibody positive or Treponema pallidum antibody positive.
• Severe hyperlipidemia (triglycerides \> 1000 mg/dL).
• Uncontrolled concomitant disease or infectious disease (need to be judged by the investigator based on clinical practice).
• Subject had undergone splenectomy and were scheduled to undergo splenectomy during the study period.

Sponsors & Collaborators

• He Huang: lead
• Lingyi Biotech Co., Ltd.: collaborator

Study Sites (1)

The First Affiliated Hospital of Zhejiang University School of Medicine

Hanzhou, Zhejiang, 310003, China

RECRUITING

Related Publications (12)

• Nabizadeh A, Amani B, Kadivar M, Toroski M, Asl AA, Bayazidi Y, Mojahedian M, Davari M. The Clinical Efficacy of Imiglucerase versus Eliglustat in Patients with Gaucher's Disease Type 1: A Systematic Review. J Res Pharm Pract. 2018 Oct-Dec;7(4):171-177. doi: 10.4103/jrpp.JRPP_18_24.

  PMID: 30622983 BACKGROUND

• Barranger JA, Brady RO, Grabowski GA, Mankin H, Mistry PK, Weinreb NJ. Position statement: National Gaucher Foundation Medical Advisory Board, January 7, 2014. Am J Hematol. 2014 May;89(5):457-8. doi: 10.1002/ajh.23687. Epub 2014 Mar 7. No abstract available.

  PMID: 24488939 BACKGROUND

• Franco M, Reihani N, Marin M, De Person M, Billette de Villemeur T, Rose C, Colin Y, Moussa F, Belmatoug N, Le Van Kim C. Effect of velaglucerase alfa enzyme replacement therapy on red blood cell properties in Gaucher disease. Am J Hematol. 2017 Sep;92(9):E561-E563. doi: 10.1002/ajh.24816. Epub 2017 Jul 19. No abstract available.

  PMID: 28621801 BACKGROUND

• Kuter DJ, Wajnrajch M, Hernandez B, Wang R, Chertkoff R, Zimran A. Open-label, expanded access study of taliglucerase alfa in patients with Gaucher disease requiring enzyme replacement therapy. Blood Cells Mol Dis. 2020 May;82:102418. doi: 10.1016/j.bcmd.2020.102418. Epub 2020 Feb 24.

  PMID: 32146279 BACKGROUND

• Bennett LL, Fellner C. Pharmacotherapy of Gaucher Disease: Current and Future Options. P T. 2018 May;43(5):274-309.

  PMID: 29719368 BACKGROUND

• Tsai P, Lipton JM, Sahdev I, Najfeld V, Rankin LR, Slyper AH, Ludman M, Grabowski GA. Allogenic bone marrow transplantation in severe Gaucher disease. Pediatr Res. 1992 May;31(5):503-7. doi: 10.1203/00006450-199205000-00019.

  PMID: 1603628 BACKGROUND

• Konkle BA, Walsh CE, Escobar MA, Josephson NC, Young G, von Drygalski A, McPhee SWJ, Samulski RJ, Bilic I, de la Rosa M, Reipert BM, Rottensteiner H, Scheiflinger F, Chapin JC, Ewenstein B, Monahan PE. BAX 335 hemophilia B gene therapy clinical trial results: potential impact of CpG sequences on gene expression. Blood. 2021 Feb 11;137(6):763-774. doi: 10.1182/blood.2019004625.

  PMID: 33067633 BACKGROUND

• Nathwani AC, Reiss UM, Tuddenham EG, Rosales C, Chowdary P, McIntosh J, Della Peruta M, Lheriteau E, Patel N, Raj D, Riddell A, Pie J, Rangarajan S, Bevan D, Recht M, Shen YM, Halka KG, Basner-Tschakarjan E, Mingozzi F, High KA, Allay J, Kay MA, Ng CY, Zhou J, Cancio M, Morton CL, Gray JT, Srivastava D, Nienhuis AW, Davidoff AM. Long-term safety and efficacy of factor IX gene therapy in hemophilia B. N Engl J Med. 2014 Nov 20;371(21):1994-2004. doi: 10.1056/NEJMoa1407309.

  PMID: 25409372 BACKGROUND

• Xu YH, Quinn B, Witte D, Grabowski GA. Viable mouse models of acid beta-glucosidase deficiency: the defect in Gaucher disease. Am J Pathol. 2003 Nov;163(5):2093-101. doi: 10.1016/s0002-9440(10)63566-3.

  PMID: 14578207 BACKGROUND

• Sun Y, Zhang W, Xu YH, Quinn B, Dasgupta N, Liou B, Setchell KD, Grabowski GA. Substrate compositional variation with tissue/region and Gba1 mutations in mouse models--implications for Gaucher disease. PLoS One. 2013;8(3):e57560. doi: 10.1371/journal.pone.0057560. Epub 2013 Mar 8.

  PMID: 23520473 BACKGROUND

• Chen RL, Hou JW, Chang PY, Tsai FJ, Wang PJ. Matched unrelated bone marrow transplantation without splenectomy for a child with Gaucher disease caused by homozygosity of the L444P mutation, who also suffered from schizencephaly. J Pediatr Hematol Oncol. 2007 Jan;29(1):57-9. doi: 10.1097/MPH.0b013e3180308793.

  PMID: 17230068 BACKGROUND

• Chowdary P, Shapiro S, Makris M, Evans G, Boyce S, Talks K, Dolan G, Reiss U, Phillips M, Riddell A, Peralta MR, Quaye M, Patch DW, Tuddenham E, Dane A, Watissee M, Long A, Nathwani A. Phase 1-2 Trial of AAVS3 Gene Therapy in Patients with Hemophilia B. N Engl J Med. 2022 Jul 21;387(3):237-247. doi: 10.1056/NEJMoa2119913.

  PMID: 35857660 BACKGROUND

Related Links

• A Phase I/II, Open label, Multicentre, Ascending Single Dose, Safety Study of a Novel Adeno associated Viral Vector (FLT180a) in Patients With Haemophilia B 2020
• Package Insert - HEMGENIX
• WHOQOL - Files

MeSH Terms

Conditions

Gaucher Disease

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

Central Study Contacts

He Huang, PhD

CONTACT

0571-87236703; hehuangyu@126.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief physician

Model Details: A Prospective, Single-center, Open-label, Single-arm study

Study Record Dates

• First Submitted: November 20, 2023
• First Posted: December 8, 2023
• Study Start: November 15, 2023
• Primary Completion (Estimated): December 17, 2026
• Study Completion (Estimated): December 17, 2031
• Last Updated: February 14, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)