Evaluating VGN-R13 for treating ALS

An Open, Dose-Escalation Early Phase Clinical Study to Evaluate the Tolerability, Safety, and Efficacy of Intrathecal of VGN-R13 in Patients with Amyotrophic Lateral Sclerosis (ALS)

This study is testing a new gene therapy called VGN-R13 to see if it can safely help people with ALS feel better.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 6 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Tongji Hospital (Academic / other)
• Locations: 1 site (Wuhan, Hubei)
• Trial ID: NCT06849609 on ClinicalTrials.gov

What this trial studies

This trial aims to assess the safety and efficacy of VGN-R13, a gene therapy, delivered intrathecally to patients diagnosed with Amyotrophic Lateral Sclerosis (ALS). The study includes a screening period, treatment period, and follow-up period lasting up to 52 weeks post-administration. Participants will receive prophylactic immunosuppressive therapy on the day of treatment, and their health will be monitored through scheduled assessments to evaluate the treatment's impact. The study seeks to provide a potential new therapeutic option for a condition currently lacking effective treatments.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with a confirmed diagnosis of ALS and disease duration of less than 2 years.

Not a fit: Patients with ALS caused by specific genetic mutations in the SOD1 or FUS genes may not benefit from this treatment.

Why it matters

Potential benefit: If successful, this treatment could offer a new hope for patients with ALS by potentially slowing disease progression or improving quality of life.

How similar studies have performed: While gene therapy for ALS is a novel approach, similar studies have shown promise in targeting neurodegenerative diseases, though this specific treatment is untested.

Eligibility criteria

key Inclusion Criteria:

1. Fully understand the purpose and risks of the study and voluntarily provide a signed and dated informed consent form.
2. Aged ≥18 years, male or female;
3. A diagnosis of ALS according to the World Federation of Neurology El Escorial criteria (revised according to the Airlie House Conference 1998 \[Brooks 2000\]), and confirmed through genetic diagnosis to exclude pathogenic mutations in the superoxide dismutase 1 (SOD1) and/or FUS genes;
4. The duration of the disease from the first symptom (any ALS symptom) prior to the screening must be less than 2 years (inclusive);
5. Forced Vital Capacity (FVC) adjusted for gender, age, and height (sitting position) ≥50% of the predicted value.
6. Discontinued riluzole for more than five half-lives prior to screening (and is not expected to resume during the study) or has been on a stable dose of riluzole for ≥30 days and continue to maintain this dose during the study period.
7. Discontinued edaravone for more than five half-lives prior to screening (and is not expected to resume edaravone during the study) or is receiving the standard edaravone treatment regimen at screening and has maintained a stable dose for ≥60 days (two treatment cycles) prior to administration, and continue to maintain this dose during the study period.

Key Exclusion Criteria:

1. There are other diseases related to motor neuron dysfunction (progressive bulbar palsy, primary lateral sclerosis, cervical spondylosis, lumbar spondylosis, etc., idiopathic inflammatory myopathy), which may confuse or cover up the diagnosis of ALS.
2. Presence of risk for increased or uncontrolled bleeding and/or risk of bleeding that is not managed optimally and could place a participant at an increased risk for intraoperative or postoperative bleeding. These could include, but are not limited to, anatomical factors at or near the LP site (e.g., vascular abnormalities, neoplasms, or other abnormalities) and underlying disorders of the coagulation cascade, platelet function, or platelet count (e.g., hemophilia, Von Willebrand's disease, liver disease).
3. Current severe liver or kidney or cardiovascular disease or coagulation dysfunction, autoimmune deficiency, or uncontrolled autoimmune disease or need immunosuppressive long-term treatment, poorly controlled diabetes (HBA1C ≥7% at screening) or high blood pressure, presence of sever gastrointestinal ulcers or history of gastrointestinal bleeding;
4. Presence of active infection that needs system treatment;
5. Presence or history of malignant tumors within 5 years prior to screening;
6. Significant cognitive impairment, clinical dementia, or unstable psychiatric illness, including psychosis, suicidal ideation, suicide attempt, or untreated major depression ≤ 90 days, as determined by the Investigator.
7. Current using medications including, drugs, herbal or OTC medications that strongly inhibit or induce CYP3A4 or P-glycoprotein (P-gp), e.g., metoclopramide, grapefruit juice, ketoconazole, erythromycin;
8. Received another drug for the treatment of ALS disease (including but not limited to sodium phenylbutyrate (PB), taurine diol (TURSO), tauroursodeoxycholic acid (TUDCA) within 1 month before the first dose) or ursodeoxycholic acid (UDCA), biologics or Other investigational drugs with a discontinuation period shorter than five half-lives;
9. Anticipated need, in the opinion of the Investigator, for administration of any antiplatelet or anticoagulant medication (e.g., clopidogrel) for 7 days before or 48 hours after an LP；
10. Received systemic immunosuppressive therapy within 3 months prior to screening;
11. Presence of an implanted shunt for the drainage of CSF or an implanted CNS catheter；
12. Presence of an implanted shunt for the drainage of CSF or an implanted CNS catheter；
13. Participation in gene therapy or stem cell transduction therapy at any time prior to screening；
14. Positive test result for HIV, positive treponemal antibody for syphilis, Active hepatitis B or hepatitis C infection, Active tuberculosis infection;
15. Clinically significant abnormalities in hematology or clinical chemistry parameters, as determined by the Investigator, which would render the participant unsuitable for enrollment;
16. Clinically significant, as determined by the Investigator, 12-lead ECG abnormalities, including corrected QT interval using Fridericia's correction method of \> 450 ms for males and \> 470 ms for females;
17. History of systemic hypersensitivity reaction to investigational product, the excipients contained in the formulation, or prophylactic immunosuppressant;
18. Contraindicated use of corticosteroids and sirolimus;
19. History of drug abuse or alcoholism within ≤ 6 months of study enrollment that would limit participation in the study, as determined by the Investigator;
20. Alcohol abuse (drinking more than 14 units of alcohol per week) or smoking more than 5 cigarettes per day on average in the 6 months prior to screening;
21. Pregnant or breastfeeding women;
22. Other unspecified reasons that, in the opinion of the Investigator or Sponsor, make the participant unsuitable for enrollment;

Where this trial is running

Wuhan, Hubei

• TongJi Hospital — Wuhan, Hubei, China (Recruiting)

Study contacts

• Study coordinator: Hong Chen

Conditions Amyotrophic Lateral Sclerosis