Study is to Assess the Safety and Tolerability of VTx-002... | NCT07287397

ID	Type	Description	Link
2025-522697-37-00	EU Trial (CTIS) Number
PIONEER-ALS	Other Identifier	VectoryTherapeutics

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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	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	Genetic: VTx-002 Drug: Preventative (Prophylactic) Medication - Corticosteroids: Methylprednisolone

Interventions

Name	Type	Description	Arm Group Labels	Other Names
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)

Outcomes Module

Primary Outcomes

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.

Secondary Outcomes

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.

Other Outcomes

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

Eligibility Module

Eligibility 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).

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

ID	Term
D013118	Spinal Cord Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D016472	Motor Neuron Disease
D019636	Neurodegenerative Diseases
D057177	TDP-43 Proteinopathies
D009468	Neuromuscular Diseases
D057165	Proteostasis Deficiencies
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases

ID	Term
D011241	Prednisone
D011239	Prednisolone

ID	Term
D011244	Pregnadienediols
D011245	Pregnadienes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D011246	Pregnadienetriols