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

NCT07287397 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: VTx-002-01-0012025-522697-37-00PIONEER-ALS
• Study Type: interventional
• Target: 12
• Locations: 4 countries
• Sites: 11

Brief Summary

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.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

ALS

Outcome Measures

Primary Outcomes (7)

• 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 1. 6 months after Gene Therapy Group 1 receive the single dose treatment 2. 6 months after Gene Therapy Group 2 receive the single dose treatment 3. 12 months after Gene Therapy Group 1 receive the single dose treatment 4. 12 months after Gene Therapy Group 2 receive the single dose treatment

  At month 6 and month 12

Secondary Outcomes (6)

• To assess whether VTx-002 works to prevent the progression of ALS and what dose can be used for future clinical studies.

  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.

  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.

  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.

  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.

  At month 6 and month 12

Other Outcomes (6)

• To assess changes in biomarkers

  Over 5 years

• To assess changes in muscle strength assessments from baseline.

  Measured at month 6 and month 12

• To assess disease severity and improvement

  over 12 months

Study Arms (2)

Gene Therapy Group 1: Dose 1 (Low Dose)

EXPERIMENTAL

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: Optional Rescue Medication: Methylprednisolone The study doctor may administer corticosteroids (methylprednisolone or prednisone) if a participant experiences immune reactions or other side effects.

Genetic: VTx-002; Drug: Optional Rescue medication - Corticosteroids: Methylprednisolone

Gene Therapy Group 2: Dose 2 (High Dose)

EXPERIMENTAL

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: Optional Rescue Medication - Methylprednisolone The study doctor may administer corticosteroids (methylprednisolone or prednisone) if a participant experiences immune reactions or other side effects.

Genetic: VTx-002; Drug: Optional Rescue medication - Corticosteroids: Methylprednisolone

Interventions

VTx-002 GENETIC

An investigational gene therapy targeting a specific protein.

Gene Therapy Group 1: Dose 1 (Low Dose); Gene Therapy Group 2: Dose 2 (High Dose)

Optional Rescue medication - Corticosteroids: Methylprednisolone DRUG

This intervention will only be administered if the study doctor concludes this is necessary based on the review of clinical and laboratory findings.

Also known as: Prednisone, Prednisolone

Gene Therapy Group 1: Dose 1 (Low Dose); Gene Therapy Group 2: Dose 2 (High Dose)

Eligibility Criteria

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

You may qualify if:

• Capable of, and willing to, provide written informed consent and comply with study procedures, including visits to the study site and visit requirements
• Male or female ≥ 18 years of age
• Has a diagnosis of ALS according to the El Escorial criteria (Brooks, et al., 2000) (probable, laboratory results supported; clinically probable, clinically definite)
• Confirmed absence of ALS caused by FUS and SOD1 gene mutations confirmed by laboratory tests.
• A maximum of 18 months since first appearance of weakness (e.g., limb weakness, dysarthria, dysphagia, shortness of breath)
• Erect (seated) SVC % predicted ≥ 80% at Screening
• Treatment Research Initiative to Cure ALS (TRICALS) risk score between -2 and -6 at Screening
• 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).
• 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
• 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
• Women of nonchildbearing potential must be post-menopausal or surgically sterile (e.g. hysterectomy, bilateral tubal ligation, ovaries removed)

You may not qualify if:

• 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
• Spinal, cervical, or brain MRI/MRA indicating clinically significant abnormality
• Presence of tracheostomy and feeding tube at Screening
• Contraindications to corticosteroid use (e.g. due to osteoporosis, uncontrolled blood pressure, diabetes or cholesterol).
• \. 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.
• \. 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
• \. Use of blood thinners (e.g., warfarin, heparin, and novel oral anticoagulants) and being unable to safely stop them before certain study procedures.
• \. Contraindications to imaging methods MRI, MRA, CT due to claustrophobia and/or intolerance to contrast agents.
• \. Contraindications to general anaesthesia (GA) or deep sedation
• Positive test for illegal drugs (except prescribed medications or permitted medicinal/recreational marijuana if used responsibly)
• \. 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

Sponsors & Collaborators

• Vector Y Therapeutics: lead

Study Sites (11)

St Joseph's Hospital and medical Center - Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

NOT YET RECRUITING

University of California San Diego Medical Center

San Diego, California, 92121, United States

RECRUITING

Mayo Clinic in Florida

Jacksonville, Florida, 32224, United States

RECRUITING

University of Miami School of Science

Miami, Florida, 33136, United States

NOT YET RECRUITING

Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

NOT YET RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

NOT YET RECRUITING

UZ Leuven

Leuven, Belgium

NOT YET RECRUITING

UMC Utrecht

Utrecht, Netherlands

NOT YET RECRUITING

Kings College Hospital

London, SE5 9RS, United Kingdom

NOT YET RECRUITING

Royal Hallamshire Hospital

Sheffield, S10 2JF, United Kingdom

NOT YET RECRUITING

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Prednisone; Prednisolone

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienetriols

Central Study Contacts

Dr Olga Uspenskaya Chief medical Officer, VectorY Therapeutics, M.D; PhD

CONTACT

patients@vectorytx.com; patients@vectorytx.com

Study Design

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

Model Details: All participants will receive a single injection of the study drug. The study will use 2 different dose levels of the study drug. Participants will be assigned to 1 of 2 groups: Group 1 (Low dose) or Group 2 (High dose). Each group will have 6 participants. The dose that participants receive will depend on their time of joining the study. Dosing will be staggered as a safety precaution with a safety monitoring committee review of health-related information in between each participant being dosed.

Study Record Dates

• First Submitted: November 19, 2025
• First Posted: December 17, 2025
• Study Start: December 19, 2025
• Primary Completion (Estimated): October 15, 2027
• Study Completion (Estimated): October 15, 2027
• Last Updated: April 28, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (7); NL (1); BE (1); GB (2)