Study is to Assess the Safety and Tolerability of VTx-002 in Participants With ALS (ALS)

Phase 1/2 Investigation of Novel Experimental Regimen in Amyotrophic Lateral Sclerosis (Pioneer-ALS): An Open-Label, Uncontrolled, Multicenter Study to Assess the Safety and Tolerability of Two Doses of VTx-002

PIONEER-ALS is a Phase 1/2, multicenter, open-label, ascending dose, uncontrolled, first-in-human study that will evaluate the safety, tolerability and effects on clinical and biomarker endpoints of intracisternal administration of Vtx-002 in participants with Amyotrophic Lateral Sclerosis (ALS).

Two escalating dose (low dose and high dose) cohorts are planned. The duration of the study will be a maximum of 5 years and 5 weeks (265 weeks) for each participant. The screening period may last up to 5 weeks to complete screening procedures.

Study Overview

• Status: Recruiting
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Genetic: VTx-002; Drug: Preventative (Prophylactic) Medication - Corticosteroids: Methylprednisolone

Detailed Description

All participants will receive a single injection of the study drug. During the first year of the study there will be 12 visits to the study center, including an overnight stay after dosing of at least 1 night. There will be a further 4 remote visits (telephone or video call).

From Year 2-5 there will be 8 further visits. These will be every 6 months and will be either in-person at the study site or remote (telephone or video call) if needed or preferred.

Throughout the 5-year observation period, there will be up to 20 study visits to complete follow-up tests and assessments and monitor the ongoing effects of the study drug.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Dr Olga Uspenskaya Chief medical Officer, VectorY Therapeutics, M.D; PhD; Phone Number: patients@vectorytx.com; Email: patients@vectorytx.com

Study Locations

• Belgium
  • Leuven, Belgium
    • Not yet recruiting
    • UZ Leuven
    • Contact: Evi Parente Study Coordinator; Phone Number: + 32 1638668; Email: evi.parente@uzleuven.be
    • Contact: Ann Dhondt Study Coordinator; Phone Number: + 32 16347577; Email: ann.dhondt@uzleuven.be
    • Principal Investigator: Dr Philip Van Damme, Doctor of Medicine
• Netherlands
  • Utrecht, Netherlands
    • Not yet recruiting
    • UMC Utrecht
    • Contact: Prof Leonard Van Den Berg, Doctor of Medicine; Phone Number: +31 887555555; Email: l.h.vandenberg@umcutrecht.nl
    • Principal Investigator: Prof Leonard Van Den Berg, Doctor of Medicine
• United Kingdom
  • London, United Kingdom, SE5 9RS
    • Not yet recruiting
    • Kings College Hospital
    • Contact: Dr Ammar Al-Chalabi, Doctor of Medicine; Phone Number: +44 2032991778; Email: ammar.al-chalabi@kcl.ac.uk
  • Sheffield, United Kingdom, S10 2JF
    • Not yet recruiting
    • Royal Hallamshire Hospital
    • Contact: Dr Chris McDermott, Doctor of medicine; Phone Number: +44 114 226 1049
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Not yet recruiting
      • St Joseph's Hospital and medical Center - Barrow Neurological Institute
      • Principal Investigator: Dr Shafeeq Ladha, Doctor of Medicine
      • Contact: Dr S Ladha, Doctor of Medicine; Phone Number: (602) 406-6262; Email: fulton.research@commonspirit.org
  • California
    • San Diego, California, United States, 92121
      • Recruiting
      • University of California San Diego Medical Center
      • Contact: Dr John Ravits, Doctor of Medicine; Phone Number: (858) 246-1154; Email: jravits@health.ucsd.edu
      • Principal Investigator: Dr John Ravits, Doctor of Medicine
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic in Florida
      • Contact: Dr Bjorn Oskarsson, Doctor of Medicine; Phone Number: (904) 953-0407; Email: oskarsson.bjorn@mayo.edu
      • Principal Investigator: Dr Bjorn Oskarsson, Doctor of Medicine
    • Miami, Florida, United States, 33136
      • Not yet recruiting
      • University of Miami School of Science
      • Contact: Dr Michael Benatar, Doctor of Medicine; Phone Number: (305) 243-6480; Email: mbenatar@med.miami.edu
      • Principal Investigator: Dr Michael Benatar, Doctor of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital
      • Principal Investigator: Dr Doreen Ho, Doctor of Medicine
      • Contact: Winifred Asigri Study Coordinator; Phone Number: (617) 724-5659; Email: pioneeralshealey@mgb.org
  • New York
    • New York, New York, United States, 10032
      • Not yet recruiting
      • Herbert Irving Comprehensive Cancer Center
      • Contact: Dr Neil Schneider, Doctor of Medicine; Phone Number: (212) 342-3107; Email: ns327@columbia.edu
      • Principal Investigator: Dr Neil Schneider, Doctor of Medicine
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Not yet recruiting
      • University of Pennsylvania
      • Contact: Dr Colin Quinn, Doctor of Medicine; Phone Number: (703) 283-7370; Email: colin.quinn2@pennmedicine.upenn.edu
      • Principal Investigator: Dr Colin Quinn, Doctor of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Capable of, and willing to, provide written informed consent and comply with study procedures, including visits to the study site and visit requirements
2. Male or female ≥ 18 years of age
3. Has a diagnosis of ALS according to the El Escorial criteria (Brooks, et al., 2000) (probable, laboratory results supported; clinically probable, clinically definite)
4. Confirmed absence of ALS caused by FUS and SOD1 gene mutations confirmed by laboratory tests.
5. A maximum of 18 months since first appearance of weakness (e.g., limb weakness, dysarthria, dysphagia, shortness of breath)
6. Erect (seated) SVC % predicted ≥ 80% at Screening
7. Treatment Research Initiative to Cure ALS (TRICALS) risk score between -2 and -6 at Screening
8. Has a reliable caregiver/partner/legal representative willing and able to support the participant in participation in the study and to give informed consent on behalf of the participant in the case that disease progression prevents the participant of giving consent (local legal rules will apply).
9. Treatment with riluzole and/or edaravone is allowed if treatment was started and has remained at a stable dose for at least 2 weeks (riluzole) or one treatment cycle (edaravone) before the Screening visit
10. Women of childbearing potential (WOCBP) and male participants with female partners who are WOCBP must agree to use highly effective contraception during and after the study. WOCBP cannot be pregnant or breastfeeding
11. Women of nonchildbearing potential must be post-menopausal or surgically sterile (e.g. hysterectomy, bilateral tubal ligation, ovaries removed)

Key Exclusion Criteria:

1. Diagnosis of a significant CNS or peripheral nervous system disease other than ALS that may be a cause for the participant's ALS symptoms or may confound study objectives
2. Spinal, cervical, or brain MRI/MRA indicating clinically significant abnormality
3. Presence of tracheostomy and feeding tube at Screening
4. Contraindications to corticosteroid use (e.g. due to osteoporosis, uncontrolled blood pressure, diabetes or cholesterol).

5. Significant concomitant disease or condition within 6 months of Screening that could pose an unacceptable safety risk to the participant or interfere with the participant's ability to comply with study procedures, e.g. heart disease, uncontrolled diabetes, liver disease, autoimmune diseases needing strong immune-suppressing drugs, cancer, etc or a current psychiatric diagnosis.

6. Clinically significant abnormalities in laboratory test results at Screening for example poor liver or kidney function, abnormal clotting or infections such as Hepatitis or HIV

7. Use of blood thinners (e.g., warfarin, heparin, and novel oral anticoagulants) and being unable to safely stop them before certain study procedures.

8. Contraindications to imaging methods MRI, MRA, CT due to claustrophobia and/or intolerance to contrast agents.

9. Contraindications to general anaesthesia (GA) or deep sedation

10 Positive test for illegal drugs (except prescribed medications or permitted medicinal/recreational marijuana if used responsibly)

11. Generally frail or if the Investigator deems participation in the study would not be in the best interest of the participant or is likely to prohibit further participation during the study

Other protocol-defined inclusion/exclusion criteria may apply

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gene Therapy Group 1: Dose 1 (Low Dose); Gene Therapy: VTx-002 6 participants will receive dose 1 administered intra cisterna magna. Dosing of the first 3 participants will be staggered at specific timepoints apart and with a safety monitoring committee review of health-related information in between each participant being dosed. VTx-002 is a single dose therapy Drug: Preventative (Prophylactic) Medication: Methylprednisolone	Genetic: VTx-002; An investigational gene therapy targeting a specific protein.; Drug: Preventative (Prophylactic) Medication - Corticosteroids: Methylprednisolone; To reduce the risk of reactions caused by the study treatment, steroid medicines will be given in advance.; Other Names: Prednisolone; Prednisone
Experimental: Gene Therapy Group 2: Dose 2 (High Dose); Gene Therapy: VTx-002 6 participants will receive dose 2 administered intra cisterna magna. The participant dosing in group 2 will be staggered as it was in group 1. VTx-002 is a single dose therapy. Drug: Preventative (Prophylactic) Medication - Methylprednisolone	Genetic: VTx-002; An investigational gene therapy targeting a specific protein.; Drug: Preventative (Prophylactic) Medication - Corticosteroids: Methylprednisolone; To reduce the risk of reactions caused by the study treatment, steroid medicines will be given in advance.; Other Names: Prednisolone; Prednisone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of participants with treatment related adverse events (AEs) and Serious Adverse Events (SAEs)	Assessed by reviewing the nature, incidence, severity, relatedness, seriousness and outcome of treatment emergent adverse events.	Over 5 years
The number of participants with treatment related adverse events (AEs) and Serious Adverse Events (SAEs)	Assessed by reviewing laboratory values	Over 5 years
The number of participants with treatment related adverse events (AEs) and Serious Adverse Events (SAEs)	Assessed by reviewing Magnetic Resonance Imaging (MRI) findings.	Over 5 years
The number of participants with treatment related adverse events (AEs) and Serious Adverse Events (SAEs)	Assessed by review of Treatment Induced Peripheral Neuropathy Assessment Scale (TNAS) *TNAS a brief participant-reported questionnaire used to measure the severity and progression of peripheral neuropathy. Each item is rated on a scale of 0 to 10, where 0 means no symptom and 10 means the symptom is as bad as it can possibly be.	over 5 years
The number of participants with treatment related adverse events (AEs) and Serious Adverse Events (SAEs)	Assessed by reviewing cellular responses by analyzing blood samples.	Over 5 years
The number of participants with treatment related adverse events (AEs) and Serious Adverse Events (SAEs)	Assessed by reviewing scores of the Columbia Suicide Severity Rating Scale (C-SSRS) *C-SSRS is a widely used, evidence-based suicide risk assessment tool that helps identify whether someone is at risk for suicide and gauge the level of support needed. A low score is associated with a lower risk level in this brief questionnaire.	Over 5 years
The number of participants with treatment related adverse events (AEs) and Serious Adverse Events (SAEs)	Assessed by performing 4 formal interim analyses; 6 months after Gene Therapy Group 1 receive the single dose treatment; 6 months after Gene Therapy Group 2 receive the single dose treatment; 12 months after Gene Therapy Group 1 receive the single dose treatment; 12 months after Gene Therapy Group 2 receive the single dose treatment	At month 6 and month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess whether VTx-002 works to prevent the progression of ALS and what dose can be used for future clinical studies.	Changes certain blood values	At month 6 and month 12
To assess whether VTx-002 works to prevent the progression of ALS and what dose can be used for future clinical studies.	Time to assisted permanent ventilation or death	over 12 months
To assess whether VTx-002 works to prevent the progression of ALS and what dose can be used for future clinical studies.	Immune responses assessed by analyzing blood samples	Over 5 years
To assess whether VTx-002 works to prevent the progression of ALS and what dose can be used for future clinical studies.	Change in Slow Vital Capacity	At month 6 and month 12
To assess whether VTx-002 works to prevent the progression of ALS and what dose can be used for future clinical studies.	Changes in CSF values	At month 6 and month 12
To assess whether VTx-002 works to prevent the progression of ALS and what dose can be used for future clinical studies.	Change in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R)	At month 6 and month 12 *ALSFRS-R is a scale used to monitor disease progression. The 12 questions. Questions are scored from 0 to 4, with a maximum score of 48 indicating full function and a minimum score of 0 indicating significant impairment.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess changes in biomarkers	Analysis of blood samples to assess viral shedding	Over 5 years
To assess changes in muscle strength assessments from baseline.	Change in muscle strength measured by Hand-held Dynamometry	Measured at month 6 and month 12
To assess disease severity and improvement	Disease severity and improvement measured using the Clinical Global Impression (CGI) scales for Severity (CGI-S) and Improvement (CGI-I). The CGI scales each use a seven-point scale where 1 indicates less severe (CGI-S) or most improved (CGI-I) and 7 indicates more severe illness (CGI-S) or worsening of condition (CGI-I)	over 12 months
To assess changes Health Related Quality of Life	Change in Health Related Quality of Life measured using the EQ5D-L questionnaire. *The EQ5D-L is a self-completed questionnaire assessing five core dimensions (Mobility, Self-care, Usual Activities, Pain/Discomfort, Anxiety/Depression). It is scored by combining patient responses across the five dimensions and then converting to a single utility score whereby 1.0 indicates perfect health and 0 indicates death	Measured at month 6 and month 12
To assess changes Health Related Quality of Life	Change in Health Related Quality of Life measured using the ALSAQ-5 questionnaire. *The ALSAQ-5 is a brief, 5-item questionnaire used to measure the impact of Amyotrophic Lateral Sclerosis on a patient's quality of life. Five key areas are rated for difficulties and converted to a total score from 0 (worst) to 100 (best)	Measured at month 6 and month 12
To assess immunogenicity of VTx002	Assessed by the review of the immunogenicity to the capsid and transgene by analyzing blood samples.	Over 5 years

Collaborators and Investigators

• Sponsor: Vector Y Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2025
• Primary Completion (Estimated): October 15, 2027
• Study Completion (Estimated): October 15, 2027

Study Registration Dates

• First Submitted: November 19, 2025
• First Submitted That Met QC Criteria: December 11, 2025
• First Posted (Actual): December 17, 2025

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: ALS
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Metabolic Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Motor Neuron Disease; Nutritional and Metabolic Diseases; Amyotrophic Lateral Sclerosis; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienetriols; Pregnadienediols; Prednisone; Prednisolone
• Other Study ID Numbers: VTx-002-01-001; 2025-522697-37-00 (Ctis); PIONEER-ALS (Other Identifier: VectoryTherapeutics)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No