Safety and Preliminary Efficacy of NXL-001 in Patients with Ischemic Stroke

NCT06761183 | Not Yet Recruiting Early Phase 1 DMC

• 1 other identifier: KY2024-378-02
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm, open-label, single center, dose-escalation exploratory clinical study to evaluate the safety and tolerability of a single intracerebral injection of NXL-001, a NeuroD1 base gene therapy, in patients with chronic neuronal deficits from ischemic stroke.

Conditions

Ischemic Stroke

Keywords

Ischemic Stroke; Gene therapy

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of NXL-001

  Incidence of adverse events (AE) and serious adverse events (SAE) according to CTCAE 5.0

  baseline to month 3 after dose

Secondary Outcomes (11)

• Change in MRI images from baseline at month 12

  Baseline (Screening), and on day 7, month 1,3,6 and 12 after dose

• Change in PET images from baseline at month 12

  Baseline (Screening), and at month 3 and 12 after dose

• Change in the National Institutes of Health Stroke Scale (NIHSS) Total Score from baseline to month 12

  Baseline (Screening), and on day1, 7, and at month 1,3,6 and 12 after dose

• Change in the Modified Rankin Scale (mRS) Response from Baseline to Month 12

  Baseline (Screening), and on day1, 7, and at month 1,3,6 and 12 after dose

• Change in the Fugl-Meyer Assessment (FMA) from Baseline to Month 12

  Baseline (Screening), and at month 1,3,6 and 12 after dose

Study Arms (1)

intracerebral stereotactic injection of NXL-001

EXPERIMENTAL

intracerebral stereotactic injection of NXL-001: with 3 subjects in each group to receive a single stereo-tactically intracerebral injection of NXL-001 at escalating doses.

Genetic: intracerebral stereotactic injection of NXL-001

Interventions

intracerebral stereotactic injection of NXL-001 GENETIC

intracerebral stereotactic injection of NXL-001: with 3 subjects in each group to receive a single stereo-tactically intracerebral injection of NXL-001 at escalating doses.

intracerebral stereotactic injection of NXL-001

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 40-75 years, inclusive, gender is not limited.
• Clinical diagnosis of ischemic stroke confirmed by neuro-imaging（CT , MRI，et al）.
• months after the onset of ischemic stroke.
• MRI scan shows that the stroke lesion is 20-80ml in size, with cerebral motor cortex injury, and DTI shows corticospinal tract injury.
• Persisting moderate to severe motor function impairment due to stroke after standardized and guide-recommended rehabilitation therapy, characterized by baseline NIHSS score of 6-20 points, and a motor score of 3-4 on the affected upper or lower limb.
• Expected survival ≥ 12 months.
• The patient or his/her legal representative clearly understands, voluntarily participates in the study and signs the informed consent form.
• The subject is willing and able to return for follow-up visits as required by the trial protocol.
• Able to undergo rehabilitation training and treatment;
• Male and female subjects participating in the clinical study must agree to use an adequate birth control method for at least 6 months after administration

You may not qualify if:

• Motor deficit due to ischemic stroke of posterior circulation.
• Motor deficit due to any other causes.
• History of epilepsy.
• History of encephalitis, meningitis, multiple sclerosis or other central nervous system infections.
• History of intracranial hemorrhage and subarachnoid hemorrhage.
• History of severe head trauma within the past 5 years.
• Any contraindications to MRI scanning (such as implanted pacemaker, infusion pump etc.).
• Serum anti-AAV9 antibody titers ≥ 1:100
• History of malignant tumors within 5 years before screening (except for adequately treated cervical carcinoma in situ, papillary thyroid cancer, basal cell or squamous epithelial cell skin cancer, localized prostate cancer after radical surgery, and breast ductal carcinoma in situ).
• Active infections, including but not limited to human immunodeficiency virus (HIV), hepatitis A, B or C, syphilis, etc.
• Received any investigational drugs within 3 months (or 5 half-lives of the investigational drug, whichever is longer) of initial screening.
• Received any other cell and/or gene therapy for stroke.
• Requirement for anticoagulants.
• Intermittent use of oral anti-spasticity medications (stop/start date from 1-month prior-to and 3-month post- NXL-001 administration). Use of oral anti-spasticity medications are acceptable if they have been taken regularly for at least one month prior to NXL-001 administration).
• Pregnant or lactating female subjects.

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead

Study Sites (1)

Beijing Tiantan Hospital

Beijing, Beijing Municipality, 10070, China

Location

Related Publications (5)

• Ma NX, Puls B, Chen G. Transcriptomic analyses of NeuroD1-mediated astrocyte-to-neuron conversion. Dev Neurobiol. 2022 Jul;82(5):375-391. doi: 10.1002/dneu.22882. Epub 2022 May 23.

  PMID: 35606902 BACKGROUND

• Kuwabara T, Hsieh J, Muotri A, Yeo G, Warashina M, Lie DC, Moore L, Nakashima K, Asashima M, Gage FH. Wnt-mediated activation of NeuroD1 and retro-elements during adult neurogenesis. Nat Neurosci. 2009 Sep;12(9):1097-105. doi: 10.1038/nn.2360. Epub 2009 Aug 23.

  PMID: 19701198 BACKGROUND

• Wu S, Wu B, Liu M, Chen Z, Wang W, Anderson CS, Sandercock P, Wang Y, Huang Y, Cui L, Pu C, Jia J, Zhang T, Liu X, Zhang S, Xie P, Fan D, Ji X, Wong KL, Wang L; China Stroke Study Collaboration. Stroke in China: advances and challenges in epidemiology, prevention, and management. Lancet Neurol. 2019 Apr;18(4):394-405. doi: 10.1016/S1474-4422(18)30500-3.

  PMID: 30878104 BACKGROUND

• Zerna C, Hegedus J, Hill MD. Evolving Treatments for Acute Ischemic Stroke. Circ Res. 2016 Apr 29;118(9):1425-42. doi: 10.1161/CIRCRESAHA.116.307005.

  PMID: 27126651 BACKGROUND

• Zhou M, Wang H, Zeng X, Yin P, Zhu J, Chen W, Li X, Wang L, Wang L, Liu Y, Liu J, Zhang M, Qi J, Yu S, Afshin A, Gakidou E, Glenn S, Krish VS, Miller-Petrie MK, Mountjoy-Venning WC, Mullany EC, Redford SB, Liu H, Naghavi M, Hay SI, Wang L, Murray CJL, Liang X. Mortality, morbidity, and risk factors in China and its provinces, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2019 Sep 28;394(10204):1145-1158. doi: 10.1016/S0140-6736(19)30427-1. Epub 2019 Jun 24.

  PMID: 31248666 BACKGROUND

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Central Study Contacts

Zhu Yahui, MD

CONTACT

0086-13439182912; zhuyahuidr@sina.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief physician, Professor

Model Details: intracerebral stereotactic injection of NXL-001：with 3 subjects in each group to receive a single stereo-tactically intracerebral injection of NXL-001 at escalating doses.

Study Record Dates

• First Submitted: December 27, 2024
• First Posted: January 7, 2025
• Study Start: January 31, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 7, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)