A Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of Intracerebral Injection of LY-N001 Injection for the Treatment of Moderate to Advanced Parkinson's Disease With GBA1 Mutations

NCT07685444 | Not Yet Recruiting Early Phase 1

• 1 other identifier: LY-N001-PD-IIT-001-1
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, single-arm, single-dose clinical study designed to evaluate the safety, tolerability, efficacy, immunogenicity, pharmacodynamic (PD) and pharmacokinetic (PK) profiles of LY-N001 Injection in patients with moderate-to-advanced Parkinson's disease carrying GBA1 mutations. The study consists of a main study phase and a long-term follow-up phase.

Conditions

Parkinson's Disease (PD)

Keywords

gene therapy; GBA1-mutant Parkinson's disease

Outcome Measures

Primary Outcomes (2)

• Incidence of dose-limiting toxicity (DLT) events occurring within at least 28 days following a single intracranial administration of LY-N001

  DLT events will be assessed per CTCAE Version 6.0.

  Within 28 days post-administration

• Incidence of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) occurring during the treatment period

  All AEs and SAEs will be graded per CTCAE Version 6.0 and adjudicated in accordance with SAE criteria.

  Within 52 weeks post-administration

Secondary Outcomes (14)

• Change from baseline in Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) motor examination scores during OFF and ON medication states

  Within 52 weeks post-administration

• Parkinson's disease medication use: changes in daily oral levodopa (L-DOPA) dose or levodopa equivalent dose (LED)

  within 52 weeks post-administration

• Motor fluctuations assessed via patient diaries: changes in "ON" time without dyskinesia or without troublesome dyskinesia, and changes in "OFF" time

  Within 52 weeks post-administration

• Changes in scores of the MDS Unified Parkinson's Disease Rating Scale (MDS-UPDRS Part I, MDS-UPDRS Part II and MDS-UPDRS Part IV)

  Within 52 weeks post-administration

• Change from baseline in Mini-mental State Examination (MMSE) score

  Within 52 weeks post-administration

Study Arms (3)

LY-N001 Dose Cohort 1

EXPERIMENTAL

LY-N001 is administered via a single intracerebral injection at Dose Cohort 1.

Genetic: LY-N001 Injection

LY-M003 Dose Cohort 2

EXPERIMENTAL

LY-N001 is administered via a single intracerebral injection at Dose Cohort 2.

Genetic: LY-N001 Injection

LY-N001 Dose De-escalation Cohort

EXPERIMENTAL

LY-N001 is administered via a single intracerebral injection at Dose De-escalation Cohort

Genetic: LY-N001 Injection

Interventions

LY-N001 Injection GENETIC

LY-N001 Injection shall be administered as a single intracerebroventricular (ICV) injection, with one administration only

LY-M003 Dose Cohort 2; LY-N001 Dose Cohort 1; LY-N001 Dose De-escalation Cohort

Eligibility Criteria

• Age: 30 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 30 to 70 years inclusive; both males and females are eligible.
• The participant fully understands the purpose, nature, procedures of the study and potential adverse events, voluntarily agrees to take part in the study and signs the informed consent form (ICF).
• Participants with clinically diagnosed idiopathic Parkinson's disease (PD) meeting the 2015 Movement Disorder Society (MDS) diagnostic criteria for idiopathic PD.
• Participants carrying at least one pathogenic GBA1 variant.
• Duration of PD disease ≥ 3 years.
• Off-state Hoehn-Yahr stage ranges from 2.5 to 4.
• Neutralizing antibody titer against AAV ≤ 1:200.
• The off-state MDS-UPDRS Part III (see Appendix 6 for MDS-UPDRS Part III motor examination) score is greater than 25, with either a ≥30% improvement rate on the acute levodopa challenge test, or an average daily off time of ≥2.5 hours over 3 consecutive days.
• Investigators determined that patients must receive a stable dose of dopaminergic medications, including levodopa, for a minimum of 4 weeks prior to surgery.
• Acceptable laboratory test values shall be obtained during the screening period and prior to administration (Day -3)：a).Hemoglobin ≥ 100 g/L; b).Platelets ≥ 100 × 10⁹/L; c). Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) ≤ 2 × upper limit of normal (ULN); d).Total bilirubin ≤ 2 × upper limit of normal (ULN); e).Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min.
• Demonstrates good treatment adherence and ability to attend scheduled follow-up visits; the participant shall be capable of accurately completing the Parkinson's disease (PD) diary during follow-up, or the participant's family member, legal guardian or caregiver may assist with diary completion.
• The participant agrees to postpone any other planned elective neurosurgical procedures (excluding emergent life-threatening neurosurgical operations occurring during the study), including Deep Brain Stimulation (DBS), until completion of the 52-week follow-up period, unless DBS treatment is recommended by a specialist in the participant's best interest.
• The participant agrees not to participate in any other therapeutic intervention studies during the study period and shall not take any other medications that may interfere with treatment other than those specified in the protocol.
• The participant agrees to refrain from receiving any vaccinations within 30 days after surgery.
• The participant must be willing to refrain from donating blood, organs, tissues or cells at any time following treatment administration.

You may not qualify if:

• Atypical or secondary parkinsonism (including Parkinson-plus syndromes, hereditary parkinsonism, drug-induced parkinsonism, etc.).
• Patients with clinically confirmed LRRK2 mutation.
• Previous history of pallidotomy, Deep Brain Stimulation (DBS) surgery, striatal surgery, extrapyramidal surgery, stereotactic brain surgery or other brain surgeries; or any other surgical history judged by the investigators to interfere with the subject's participation in this study.
• Participants with previous head Computed Tomography (CT) / Magnetic Resonance Imaging (MRI) showing neurological diseases such as brain trauma, vascular malformations, hydrocephalus, brain tumors; subjects with hyperintense white matter signals on MRI indicating risk of intracranial hemorrhage; subjects with cerebrovascular lesions or microbleeds on SWI (Susceptibility-Weighted Imaging); subjects with vulnerable plaques or intraplaque hemorrhage of craniocervical arteries on HR-MRI (High-Resolution Magnetic Resonance Imaging); or subjects with imaging abnormalities in the striatum or other brain regions that substantially increase surgical risks.
• The participant has a Mini-Mental State Examination (MMSE) score of less than 20.
• A Patient Health Questionnaire (PHQ) score of ≥16 indicates severe depression.
• Any severe psychiatric illnesses including epilepsy, severe anxiety, schizophrenia that are deemed unsuitable for participation in this study by the investigators, excluding mild hallucinations and similar symptoms induced by anti-Parkinsonian medications.
• Patients taking anticoagulants or antiplatelet drugs whose coagulation function has not returned to normal 10 days after drug discontinuation.
• Patients who have previously received gene therapy or cell therapy.
• Use of systemic glucocorticoids or immunosuppressive drugs within 12 weeks prior to administration, except for prophylactic immunosuppressive agents required by the protocol (excluding prophylactic immunosuppressive therapy specified in the protocol).
• Participants with unstable cardiovascular and cerebrovascular diseases, defined as clinical cardiovascular and cerebrovascular events occurring within 3 months prior to screening (e.g., unstable angina, myocardial infarction, stroke, etc.); uncontrolled diabetes mellitus with glycated hemoglobin \>8.0%; or other unstable acute or chronic diseases including infectious diseases, severe uncontrolled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg), or severe orthostatic hypotension (a drop in systolic blood pressure ≥20 mmHg or diastolic blood pressure ≥10 mmHg within 3 minutes after the participant changes from supine/squatting position to standing position).
• Positive Hepatitis B surface antigen (HBsAg) or Hepatitis B Virus Deoxyribonucleic Acid (HBV-DNA); positive Hepatitis C Virus antibody (HCV-Ab) or Hepatitis C Virus Ribonucleic Acid (HCV-RNA).For participants with a prior history of hepatitis B or hepatitis C, two samples collected at an interval of at least 3 months must test negative for all above indicators to be considered negative. Participants with spontaneously cleared or antivirally treated cleared hepatitis B or C are eligible for this study.Participants with positive Human Immunodeficiency Virus (HIV) test or positive syphilis serology.
• Participants with surgical contraindications, those who have received other surgical procedures deemed to interfere with this study by the investigators within six months, or those with other contraindications to neurosurgery.
• Participants with an average weekly alcohol intake exceeding 21 units for males or 14 units for females within 30 days prior to screening; 1 alcohol unit equals one 5 oz (150 mL) glass of red wine, 12 oz (360 mL) beer, or 1.5 oz (45 mL) distilled spirits; or participants with a history of drug dependence.
• Participants with contrast medium allergy who cannot undergo MRI, or those unable to tolerate surgical anesthesia.

Sponsors & Collaborators

• Lingyi Biotech Co., Ltd.: lead

Study Sites (1)

The First Affiliated Hospital of Anhui Medical University

Hefei, Anhui, 230022, China

Location

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Yi Wang, PhD

  The First Affiliated Hospital of Anhui Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rihong He, BD

CONTACT

+8619121572057; rihong.he@lingyimed.com

Study Design

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

Study Record Dates

• First Submitted: June 29, 2026
• First Posted: July 6, 2026
• Study Start: July 7, 2026
• Primary Completion (Estimated): July 7, 2028
• Study Completion (Estimated): December 30, 2032
• Last Updated: July 6, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)