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Phase 1/2 Study to Evaluate the Safety and Tolerability of VTx-002 in Patients with Amyotrophic Lateral Sclerosis

Trial ID: 2025-522697-37-00
Protocol: VTx-002-01-001
Sponsor: VectorY Therapeutics B.V.

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Diseases & Conditions

Amyotrophic lateral sclerosis

Objectives

The primary objective of this study is to evaluate the safety and tolerability of escalating doses of a single administration of VTx-002 in patients with amyotrophic lateral sclerosis. The secondary objectives include:

Assessment of preliminary efficacy and immunogenicity.
Determination of the optimal dosage for future clinical investigations.

Participants

The study population consists of 8 participants diagnosed with amyotrophic lateral sclerosis. Eligible individuals include both male and female participants aged 18 years or older. Selection is based on a diagnosis meeting the El Escorial criteria, with a maximum of 18 months since the initial onset of weakness. Inclusion requires a treatment research initiative to cure ALS risk score between -2 and -6 and an erect seated SVC % predicted of at least 80% at screening. The population excludes individuals with FUS or SOD1 genetic mutations. Participants may be receiving stable regimens of riluzole or edaravone. Strict contraception requirements are in place for women of childbearing potential and male participants to prevent exposure. Additionally, participants must have completed pneumococcal pneumonia and shingles vaccinations within the previous 10 years or agree to receive them during the screening period.

Plans and Procedures

This Phase 1/2, open-label, uncontrolled, multicenter study is designed to evaluate the safety and tolerability of two doses of VTx-002 administered via intracisternal injection in individuals diagnosed with amyotrophic lateral sclerosis. The research methodology focuses on assessing treatment-emergent adverse events, including laboratory values, magnetic resonance imaging findings, and cellular responses to the vector and transgene-encoded protein. Secondary endpoints include changes in the revised ALS Functional Rating Scale, slow vital capacity, and survival, as well as immunogenicity against the adeno-associated virus capsid. The study includes a screening visit to confirm eligibility based on El Escorial criteria and the absence of FUS and SOD1 mutations. Following baseline, participants will undergo follow-up assessments to monitor clinical progression and safety. The total trial duration is estimated to extend through April 2031.

Treatment

The experimental medication, VTx-002, is administered as a solution for injection via the intracisternal route. This study evaluates the safety and tolerability of a single administration of this substance in patients with amyotrophic lateral sclerosis.

The VTx-002 Diluent, containing sodium dihydrogen phosphate dihydrate, is utilized as an auxiliary solution for injection for intracisternal administration.

Efficacy

The efficacy assessment in this study of amyotrophic lateral sclerosis includes several secondary endpoints. The revised ALS Functional Rating Scale will be used to evaluate changes over 6 and 12 months. Respiratory function will be measured by the change in slow vital capacity at 6 and 12 months. Additional parameters include survival and the time to permanent assisted ventilation or death over 12 months. Immunogenicity against the adeno-associated virus capsid will also be monitored.

Inclusion and Exclusion Criteria

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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 FUS and SOD1 ALS by exclusion of pathogenic or possible pathogenic genetic mutations (per central laboratory at Screening or previous result provided by Clinical Laboratory Improvement Amendments [CLIA] certified laboratory, or EU/United Kingdom equivalent accreditation)
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). This person should have regular contact with the participant and must sign a separate partner informed consent form (ICF) indicating that she/he understands the study requirements and is willing to participate
Treatment with riluzole and/or edaravone is allowed if treatment was started and maintained at a stable regimen for at least 4 weeks for riluzole and/or for a full treatment cycle for edaravone (i.e., 14 days on AND 14 days off) before the Screening visit
Women of childbearing potential (WOCBP) and male participants with female partners who are WOCBP (based on gender assignation at birth) must agree to use highly effective (<1% failure rate) contraception for at least 30 days prior to the first dose of study medication and for the fixed period of one year following administration of the study medication. Male participants (based on gender assignation at birth) must refrain from sperm donation for the fixed period of one year following administration of the study medication; WOCBP (based on gender assignation at birth) must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline (Day 1)
Women of nonchildbearing potential must be either surgically sterile (hysterectomy, bilateral tubal ligation, salpingectomy, and/or bilateral oophorectomy at least 26 weeks before Screening) or postmenopausal, defined as spontaneous amenorrhea for at least 2 years, with follicle-stimulating hormone (FSH) level in the postmenopausal range at Screening based on the central laboratory's range
Men and WOCBP (i.e., ovulating, premenopausal, and not surgically sterile) must use a highly effective method of contraception consistently and correctly for the duration of fixed period of one year following administration of study medication. Highly effective methods of contraception are those that, alone or in combination, result in a failure rate of less than 1% per year when used consistently and correctly (i.e., perfect use) o Acceptable forms of contraception for participating WOCBP include the following: ▪ Combined (estrogen and progestogen containing) oral, intravaginal, or transdermal hormonal contraception associated with inhibition of ovulation ▪ Oral, injectable, or implantable progestogen-only hormonal contraception associated with inhibition of ovulation ▪ Intrauterine device ▪ Intrauterine hormone-releasing system ▪ Bilateral tubal ligation or bilateral tubal occlusion (performed at least 3 months prior to Screening) ▪ Vasectomized partner (performed at least 3 months prior to Screening) ▪ Sexual abstinence (no sexual intercourse) o Acceptable forms of contraception for male participants include: ▪ Sexual abstinence (no sexual intercourse) ▪ History of vasectomy (performed at least 3 months prior to Screening) plus external condom ▪ Condom with spermicide used together with highly effective female contraceptive methods if the female partner(s) is of childbearing potential (see above for list of acceptable female contraceptive methods)
Women who are in exclusively same-sex relationships (as their preferred and usual lifestyle) are not required to use contraception; male participants in same sex relationships are also required to use an external condom to prevent exposure of their partner to the IMP
Men must agree to abstain from sperm donation for the fixed period of one year following administration of the study medication and are required to use an external condom when engaging in any activity that allows for passage of ejaculate to another person during the main study period
Women must agree to abstain from egg donation for the duration of the study
Women of childbearing potential cannot be pregnant or lactating/breastfeeding and must have a negative result for the serum pregnancy test (P-human chorionic gonadotropin [P-HCG]) at Screening
Must have pneumococcal pneumonia and shingles vaccination coverage within 10 years prior to Screening or consent to these vaccinations to be performed during the Screening period
Up to date with age and gender appropriate cancer screening as per local standard of care based on Principal Investigator's (PI) judgment

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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, including evidence of prior hemorrhage, infarct > 1.5 cm3 or > 3 lacunar infarcts, or a structural abnormality deemed a contraindication to intracisternal injection
Presence of tracheostomy and feeding tube at Screening
Receipt of an experimental agent or any other investigational medicinal product, devices, stem cells, or experimental therapy within 30 days or five half-lives prior to Screening or anytime over the duration of this study
Presence of an implanted deep brain stimulation device, ventriculoperitoneal or another CSF shunt, or other implanted catheter
Hypersensitivity or contraindications to corticosteroid use (including, but not limited to, osteoporosis with vertebral fractures within 1 year prior to Screening, active peptic ulcer disease, uncontrolled hypertension, poorly controlled diabetes, uncontrolled hyperlipidemia or hypercholesterolemia as per Investigator assessment)
Concomitant disease or condition within 6 months of Screening that could interfere with, or treatment of which might interfere with, the conduct of the study or that would, in the opinion of the Investigator, pose an unacceptable safety risk to the participant or interfere with the participant's ability to comply with study procedures; including, but not limited to, the following: a. Evidence of clinically significant liver pathology, according to Investigator judgment b. Unstable autoimmune disease; autoimmune disease requiring chronic immunosuppression c. Poorly controlled/not adequately managed diabetes (glycosylated hemoglobin [HbA1c] ≥ 7% at Screening) d. History of unstable angina, myocardial infarction, chronic heart failure (New York Heart Association Class III or IV), or clinically significant conduction abnormalities (e.g., unstable atrial fibrillation) within 1 year prior to Screening e. Clinically significant 12-lead electrocardiogram (ECG) abnormalities at Screening, as determined by the Investigator f. Uncontrolled hypertension defined as: average of three systolic/diastolic blood pressure readings > 165/100 mmHg at Screening (the Investigator may re-test, if considered appropriate in their judgment), or persistent systolic/diastolic blood pressure readings > 180/100 mmHg within 3 months prior to Screening that, in the opinion of the Investigator, are indicative of chronic uncontrolled hypertension g. History of cancer within 5 years of Screening with the exception of fully excised non-melanoma skin cancers, non-metastatic prostate cancer, and fully treated ductal breast carcinoma in situ, provided it has been stable for at least 6 months h. History or current alcohol or drug abuse within 2 years of Screening i. Any current psychiatric diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, or equivalent that may interfere with participant's ability to perform study procedures and all assessments (e.g., psychosis, major depression, bipolar, mental retardation, and schizophrenia). Note: Mild depression, cognitive impairment or anxiety are not excluded if associated with participant's ALS and well controlled and if, in the opinion of the Investigator, would not interfere with participant's ability to adhere to study protocol j. At imminent risk of self-harm, based on clinical interview and responses on the C-SSRS and PI evaluation. Participants must be excluded if they report ideation with intent, with or without a plan or method (i.e., positive response to Items 4 or 5 on the C-SSRS) in the past 2 months or suicidal behavior in the past 6 months k. Any medical disorders that, in the opinion of the Investigator, could interfere with study- related procedures (including safe performance of lumbar puncture [LP] or intracisternal injection), such as prohibitive spinal diseases, bleeding diathesis, clinically significant coagulopathy, thrombocytopenia, or increased intracranial pressure l. Documented stroke or transient ischemic attack within 1 year prior to Screening m. History of seizure or unexplained blackouts within 10 years prior to Screening n. Currently active infection or a severe infection (e.g., pneumonia, septicemia, CNS infections [e.g., meningitis, encephalitis]) within 12 weeks prior to Screening
Concomitant disease or condition within 6 months of Screening that could interfere with, or treatment of which might interfere with, the conduct of the study or that would, in the opinion of the Investigator, pose an unacceptable safety risk to the participant or interfere with the participant's ability to comply with study procedures; including, but not limited to, the following: o. History of severe allergic or anaphylactic reactions p. History of hypersensitivity to any inactive ingredient of the investigational medicinal produce (IMP) (refer to the Investigator’s Brochure [IB]) or protocol-required rescue immunosuppressant medication
Clinically significant abnormalities in laboratory test results at Screening as given below (laboratory testing may be repeated with medical monitor approval): a. Total bilirubin, alanine aminotransferase (ALT), or aspartate aminotransferase (AST) > 1.5 x the upper limit of normal (ULN) b. b. Serum creatinine > 1.5 x ULN c. Hematocrit < 35% for men and < 32% for women d. Absolute neutrophil count < 1500/µL, lymphocyte count < 500/µL, platelet count < l 00,000/µL, international normalized ratio > 1.4, or other coagulopathy e. Screening thyrotropin test > 5.5 mU/L f. Activated partial thromboplastin time > 50 seconds g. Screening LP revealing CSF white blood cells (WBC) > 30 cells/mm3 or CSF protein > 70 mg/dL h. Positive result for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) with positive hepatitis B deoxyribonucleic acid (HBV DNA), hepatitis C antibody (HCVAb) with positive HCV ribonucleic acid (RNA), or human immunodeficiency virus (HIV) 1 or 2 Note: Participants with positive HBcAb and negative HBV DNA are eligible to participate. Successfully treated or naturally resolved HCV participants (undetectable HCV RNA) are eligible for enrollment
Any other abnormal Screening laboratory test result deemed clinically significant by the Investigator
Any type of prior gene or cell therapy
Immunizations (live vaccines) in the 4 weeks prior to Screening. Note: Pneumococcal and shingles vaccine administrations are allowed during the Screening period
Pregnant or breastfeeding
Use of blood thinners (e.g., warfarin, heparin, and novel oral anticoagulants) in the 2 weeks prior to Screening LP or (ICM) procedure, or the anticipated need to initiate blood thinners during the study. Antiplatelet therapies (e.g., prophylactic aspirin, clopidogrel) are acceptable if the participant is medically able to temporarily stop 48 hours to 7 days (depending on the antiplatelet medication used) prior to and at least 48 hours after intracisternal injection and LP
Contraindications or intolerance to imaging methods (MRI, MRA, computed tomography [CT]) inducing claustrophobia and/or intolerance to contrast agents used for MRI, MRA, or CT (including but not limited to gadolinium contrast agents)
Contraindications to general anesthesia (GA) or deep sedation
Positive urine test for drugs of abuse (including opiates, benzodiazepines, amphetamines, cocaine, barbiturates, and phencyclidine) without prescription and without a clear justification of the results (determined by the Investigator) at Screening and Day 1. Note: use of medical marijuana is permitted provided that the participant is on a stable regimen. It is also permitted if the participant resides in a state in which the recreational use of marijuana is legalized, so long as the participant does not meet the drug abuse criteria (as defined in the DSM-5)
Generally frail or has any medical condition, for which in view of the Investigator, participation in the study would not be in the best interest of the participant or is likely to prohibit further participation during the study
Known or suspected allergy or intolerance to the IMP (VTx-002 or constituents)

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Belgium	Not Yet Recruiting	30 Apr 2026	1
The Netherlands	Recruiting	30 Apr 2026	—
Spain	Not Recruiting	30 Apr 2026	2
Netherlands	—	—	1

Sites & Investigators

Research sites

Universitair Medisch Centrum Utrecht Katholieke Universiteit te Leuven Bellvitge University Hospital Hospital Universitario Y Politecnico La Fe

Investigators

Leonard V. D. B.Juan Francisco V. C.Philip V. D.

Investigational Products

Details about the medicinal products being studied in this clinical trial.

Product Name	Role in Trial	Formulation	Administration	Max Daily Dose	Treatment Duration	EU MP Number
VTx-002 Diluent	Other	SOLUTION FOR INJECTION	INTRACISTERNAL USE	—	—	PRD13053371
VTx-002	Test	SOLUTION FOR INJECTION	INTRACISTERNAL USE	—	—	PRD12985318
VTx-002	Test	SOLUTION FOR INJECTION	INTRACISTERNAL USE	—	—	PRD12985319

Conditions Studied in This Trial

Interventions Studied in This Trial

vaccines

Sodium Dihydrogen Phosphate Dihydrate

5 trials

Also investigated for

Angelman's syndrome 3 Amyotrophic lateral sclerosis 1 Cardiac operation 1

vaccines

VTX-002

1 trial

Also investigated for

Amyotrophic lateral sclerosis 1