Safety and tolerability of VTx-002 given into the cisterna in people with 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

This trial will test a single intracisternal injection of VTx-002 to see if it is safe and tolerated in adults with ALS.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Vector Y Therapeutics (Industry-sponsored)
• Locations: 11 sites (Phoenix, Arizona and 10 other locations)
• Trial ID: NCT07287397 on ClinicalTrials.gov

What this trial studies

PIONEER-ALS is a first-in-human, open-label Phase 1/2 study using ascending doses of VTx-002 administered as a single intracisternal injection. Two dose cohorts (low and high) will be enrolled and all participants will be followed for up to 5 years and 5 weeks with scheduled in-person and remote visits. The first year includes 12 site visits including one overnight stay after dosing, then biannual follow-up visits in years 2–5, totaling up to 20 follow-up visits. Clinical outcomes and biomarker measures will be collected throughout to monitor safety, tolerability, and any effects on disease-related measures.

Who should consider this trial

Good fit: Adults (≥18) with ALS by El Escorial criteria within 18 months of first weakness, without SOD1 or FUS mutations, with seated SVC ≥80%, a TRICALS risk score between -2 and -6, and a reliable caregiver able to support study participation are ideal candidates.

Not a fit: Patients with known SOD1 or FUS mutations, more advanced disease (onset >18 months or low respiratory function), inability to provide informed consent, or inability to attend required site visits are unlikely to be eligible or to benefit.

Why it matters

Potential benefit: If successful, VTx-002 could offer a new therapeutic approach that slows ALS progression or improves biomarkers associated with motor neuron health.

How similar studies have performed: This is a first-in-human intracisternal gene therapy approach for ALS, so there is limited clinical precedent and similar approaches remain largely unproven in humans.

Eligibility criteria

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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Where this trial is running

Phoenix, Arizona and 10 other locations

• St Joseph's Hospital and medical Center - Barrow Neurological Institute — Phoenix, Arizona, United States (Not_yet_recruiting)
• University of California San Diego Medical Center — San Diego, California, United States (Recruiting)
• Mayo Clinic in Florida — Jacksonville, Florida, United States (Recruiting)
• University of Miami School of Science — Miami, Florida, United States (Not_yet_recruiting)
• Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital — Boston, Massachusetts, United States (Recruiting)
• Herbert Irving Comprehensive Cancer Center — New York, New York, United States (Not_yet_recruiting)
• University of Pennsylvania — Philadelphia, Pennsylvania, United States (Not_yet_recruiting)
• UZ Leuven — Leuven, Belgium (Not_yet_recruiting)
• UMC Utrecht — Utrecht, Netherlands (Not_yet_recruiting)
• Kings College Hospital — London, United Kingdom (Not_yet_recruiting)
• Royal Hallamshire Hospital — Sheffield, United Kingdom (Not_yet_recruiting)

Study contacts

• Study coordinator: Dr Olga Uspenskaya Chief medical Officer, VectorY Therapeutics, M.D; PhD

Conditions Amyotrophic Lateral Sclerosis; ALS