Amyotrophic Lateral SclerosisPhase 1/2ALSNCT07287397
Study is to Assess the Safety and Tolerability of VTx-002 in Participants With ALS
A Phase 1/2 study testing VTx-002 and Preventative (Prophylactic) Medication - Corticosteroids: Methylprednisolone in people with Amyotrophic Lateral Sclerosis, run by Vector Y Therapeutics at 11 sites in 4 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- VTx-002 and Preventative (Prophylactic) Medication - Corticosteroids: Methylprednisolone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 11 sitesin 4 countries
- Study dates
- 19 Dec 2025to 15 Oct 2027
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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)
Who cannot join
- 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).
- 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
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- 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
- -
Trial locations and contacts
11 sites in 4 countries. Contact the study team or a site near you to ask about taking part.
Dr Olga Uspenskaya Chief medical Officer, VectorY Therapeutics, M.D; PhD contact
11 sites in 4 countries
United States7 sites, 7 recruiting
- Recruiting
Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital
Boston, Massachusetts, 02114
Winifred Asigri Study Coordinator, (617) 724-5659, pioneeralshealey@mgb.org
Dr Doreen Ho, Doctor of Medicine
- Recruiting
Mayo Clinic in Florida
Jacksonville, Florida, 32224
Dr Bjorn Oskarsson, Doctor of Medicine, (904) 953-0407, oskarsson.bjorn@mayo.edu
Dr Bjorn Oskarsson, Doctor of Medicine
- Not yet recruiting
University of Miami School of Science
Miami, Florida, 33136
Dr Michael Benatar, Doctor of Medicine, (305) 243-6480, mbenatar@med.miami.edu
Dr Michael Benatar, Doctor of Medicine
- Not yet recruiting
Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
Dr Neil Schneider, Doctor of Medicine, (212) 342-3107, ns327@columbia.edu
Dr Neil Schneider, Doctor of Medicine
- Recruiting
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Spriha Thapa Study Coordinator, 267-610-8822, Spriha.Thapa@pennmedicine.upenn.edu
Dr Colin Quinn, Doctor of Medicine
- Not yet recruiting
St Joseph's Hospital and medical Center - Barrow Neurological Institute
Phoenix, Arizona, 85013
Dr S Ladha, Doctor of Medicine, (602) 406-6262, fulton.research@commonspirit.org
Dr Shafeeq Ladha, Doctor of Medicine
- Recruiting
University of California San Diego Medical Center
San Diego, California, 92121
Dr John Ravits, Doctor of Medicine, (858) 246-1154, jravits@health.ucsd.edu
Dr John Ravits, Doctor of Medicine
United Kingdom2 sites, 2 recruiting
- Not yet recruiting
Kings College Hospital
London, SE5 9RS
Dr Ammar Al-Chalabi, Doctor of Medicine, +44 2032991778, ammar.al-chalabi@kcl.ac.uk
- Recruiting
Royal Hallamshire Hospital
Sheffield, S10 2JF
Dr Chris McDermott, Doctor of medicine, +44 114 226 1049, c.j.mcdermott@sheffield.ac.uk
Belgium1 site, 1 recruiting
- Recruiting
UZ Leuven
Leuven
Evi Parente Study Coordinator, + 32 1638668, evi.parente@uzleuven.be
Ann Dhondt Study Coordinator, + 32 16347577, ann.dhondt@uzleuven.be
Netherlands1 site, 1 recruiting
- Recruiting
UMC Utrecht
Utrecht
Prof Leonard Van Den Berg, Doctor of Medicine, +31 887555555, l.h.vandenberg@umcutrecht.nl
Prof Leonard Van Den Berg, Doctor of Medicine
About this study
Official title: 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.
Read the 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.
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- VTx-002, Preventative (Prophylactic) Medication - Corticosteroids: Methylprednisolone
- Keywords
- ALS
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VTx-002Genetic
An investigational gene therapy targeting a specific protein.
Preventative (Prophylactic) Medication - Corticosteroids: MethylprednisoloneDrug
Also called Prednisone, Prednisolone
To reduce the risk of reactions caused by the study treatment, steroid medicines will be given in advance.
| Study group | Role | What they receive |
|---|---|---|
| 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: Preventative (Prophylactic) Medication: Methylprednisolone Receives: Genetic: VTx-002; Drug: Preventative (Prophylactic) 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: Preventative (Prophylactic) Medication - Methylprednisolone Receives: Genetic: VTx-002; Drug: Preventative (Prophylactic) Medication - Corticosteroids: Methylprednisolone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Over 5 years
The number of participants with treatment related adverse events (AEs) and Serious Adverse Events (SAEs)
Assessed by reviewing laboratory values
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Changes certain blood values
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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)
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2025
- Study start19 Dec 2025
- Primary completion15 Oct 2027 (estimated)
- Study completion15 Oct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- 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 18 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.
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vector Y Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07287397
- Sponsor's protocol ID
- VTx-002-01-001
- Other IDs
- 2025-522697-37-00, PIONEER-ALS, 2025
- Acronym
- ALS
- Status last verified
- Sep 2026
- First submitted
- 19 Nov 2025
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No