PIONEER-ALS

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

UK Chief Investigator

Professor Chris McDermott

Research summary

PIONEER-ALS is a Phase 1/2, multicentre, 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.

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.

Current status

In setup

Recruitment target

2 participants in the UK; up to 12 participants globally

Recruitment groups

Patients with MND

Locations

• Sheffield, Principal Investigator: Chris McDermott.  In set-up, site opening soon

• London (King's College Hospital), Principal Investigator: Ammar Al-Chalabi  In set-up, site opening soon

Information about study sites

Key dates

Planned recruitment open date: July 2026

Planned recruitment end date: November 2026

Inclusion / exclusion criteria

Key Inclusion criteria

• 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)

Key Exclusion criteria

• 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

Funder & Sponsor

VectorY Therapeutics

Study design

Interventional; non-randomised, open-label tiral

Intervention

• VTx-002, an investigational gene therapy targeting a specific protein

• Preventative (Prophylactic) Medication - Corticosteroids: Methylprednisolone 

Phase

1/2

Outcome measures

Primary outcome measure

• The number of participants with treatment related adverse events (AEs) and Serious Adverse Events (SAEs)

Secondary outcome measures

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

• To assess changes in biomarkers

• To assess changes in muscle strength assessments from baseline

• To assess disease severity and improvement

• To assess immunogenicity of VTx002

• To assess changes Health Related Quality of Life