VTX-002 for Amyotrophic lateral sclerosis

Inclusion criteria

• {"criterion_text":"-Capable of, and willing to, provide written informed consent and comply with study procedures, including visits to the study site and visit requirements"}
• {"criterion_text":"-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, during the study, and for 90 days following end of study [EOS] including the long term follow-up. Male participants (based on gender assignation at birth) must refrain from sperm donation for the duration of the study and for 90 days after EOS including the long term follow-up; 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)"}
• {"criterion_text":"-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"}
• {"criterion_text":"-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 the study including the long- term follow-up. 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)"}
• {"criterion_text":"-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"}
• {"criterion_text":"-Men must agree to abstain from sperm donation for the duration of the study, including long-term follow-up 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"}
• {"criterion_text":"-Women must agree to abstain from egg donation for the duration of the study, including long-term follow-up"}
• {"criterion_text":"-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"}
• {"criterion_text":"-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"}
• {"criterion_text":"-Up to date with age and gender appropriate cancer screening as per local standard of care based on Principal Investigator's (PI) judgment"}
• {"criterion_text":"-Male or female ≥ 18 years of age"}
• {"criterion_text":"-Has a diagnosis of ALS according to the El Escorial criteria (Brooks, et al., 2000) (probable, laboratory results supported; clinically probable, clinically definite)"}
• {"criterion_text":"-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)"}
• {"criterion_text":"-A maximum of 18 months since first appearance of weakness (e.g., limb weakness, dysarthria, dysphagia, shortness of breath)"}
• {"criterion_text":"-Erect (seated) SVC % predicted ≥ 80% at Screening"}
• {"criterion_text":"-Treatment Research Initiative to Cure ALS (TRICALS) risk score between −2 and −6 at Screening"}
• {"criterion_text":"-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"}
• {"criterion_text":"-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 before the Screening visit"}

Exclusion criteria

• {"criterion_text":"-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"}
• {"criterion_text":"-Any other abnormal Screening laboratory test result deemed clinically significant by the Investigator"}
• {"criterion_text":"-Any type of prior gene or cell therapy"}
• {"criterion_text":"-Immunizations (live vaccines) in the 4 weeks prior to Screening. Note: Pneumococcal and shingles vaccine administrations are allowed during the Screening period"}
• {"criterion_text":"-Pregnant or breastfeeding"}
• {"criterion_text":"-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"}
• {"criterion_text":"-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)"}
• {"criterion_text":"-Contraindications to general anesthesia (GA) or deep sedation"}
• {"criterion_text":"-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)"}
• {"criterion_text":"-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"}
• {"criterion_text":"-Known or suspected allergy or intolerance to the IMP (VTx-002 or constituents)"}
• {"criterion_text":"-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"}
• {"criterion_text":"-Presence of tracheostomy and feeding tube at Screening"}
• {"criterion_text":"-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"}
• {"criterion_text":"-Presence of an implanted deep brain stimulation device, ventriculoperitoneal or another CSF shunt, or other implanted catheter"}
• {"criterion_text":"-Hypersensitivity or contraindications to corticosteroid use (including, but not limited to, osteoporosis with vertebral fractures within 1 year prior to Screening, uncontrolled hypertension, poorly controlled diabetes, uncontrolled hyperlipidemia or hypercholesterolemia as per Investigator assessment)"}
• {"criterion_text":"-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 list of specified conditions (e.g., clinically significant liver pathology, unstable autoimmune disease, poorly controlled diabetes with HbA1c ≥ 7%, recent cardiac events, clinically significant ECG abnormalities, uncontrolled hypertension, recent cancer, substance abuse, severe psychiatric diagnoses, imminent risk of self-harm, medical disorders interfering with LP/intracisternal injection, recent stroke/TIA, recent seizures, active severe infection)"}
• {"criterion_text":"-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 history of severe allergic or anaphylactic reactions or hypersensitivity to any inactive ingredient of the IMP or protocol-required rescue immunosuppressant medication"}
• {"criterion_text":"-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. 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"}

Primary endpoints

• {"endpoint_text":"-Nature, incidence, severity, relatedness, seriousness, and outcome of treatment-emergent adverse events (TEAEs) including: o Laboratory values o Magnetic resonance imaging (MRI) findings o Treatment-induced Peripheral Neuropathy Assessment Scale (TNAS) o Assessment of cellular responses to both the vector and the transgene encoded protein o Columbia Suicide Severity Rating Scale (C-SSRS)","definition_or_measurement_approach":"Safety measured as TEAEs with assessments from laboratory values, MRI findings, TNAS scores, cellular immune response assays to vector and transgene, and C-SSRS for suicidality."}

Secondary endpoints

• {"endpoint_text":"-Change in revised ALS Functional Rating Scale (ALSFRS-R) over 6 and 12 months","definition_or_measurement_approach":"Measured as change from baseline in ALSFRS-R score at 6 and 12 months."}
• {"endpoint_text":"-Time to permanent assisted ventilation, or death over 12 months","definition_or_measurement_approach":"Time-to-event analysis measuring time from dosing to initiation of permanent assisted ventilation or death within 12 months."}
• {"endpoint_text":"-Change in slow vital capacity (SVC) over 6 and 12 months","definition_or_measurement_approach":"Measured as change from baseline in slow vital capacity (SVC) at 6 and 12 months."}
• {"endpoint_text":"-Survival","definition_or_measurement_approach":"Overall survival assessed over the study follow-up period."}
• {"endpoint_text":"-Immunogenicity against adeno-associated virus (AAV) capsid","definition_or_measurement_approach":"Measured by immunogenicity assays detecting immune responses (antibodies/cellular) against the AAV capsid."}

Methods

• TRICALS website text (explicit recruitment material listed as 'K2_Recruitment Material_TRICALS website text') - digital/registry channel targeting ALS patients enrolled or seeking information via TRICALS
• Patient Brochure materials (K2_Recruitment material_Patient Brochure_English and language variants) - patient-facing brochures for potential participants
• Site-based recruitment via participating neurology clinics/hospitals (listed trial sites at UZ Leuven, Bellvitge University Hospital, Hospital Universitario Y Politecnico La Fe) - local site recruitment via neurology departments

Belgium

Earliest CTIS Part Ii Submission Date

17-03-2026

Latest Decision Or Authorization Date

31-03-2026

Processing Time Days

14

Number Of Sites

1

Number Of Participants

1

Spain

Earliest CTIS Part Ii Submission Date

05-02-2026

Latest Decision Or Authorization Date

06-04-2026

Processing Time Days

60

Number Of Sites

2

Number Of Participants

2

Netherlands

Earliest CTIS Part Ii Submission Date

19-03-2026

Latest Decision Or Authorization Date

01-04-2026

Processing Time Days

13

Number Of Sites

1

Number Of Participants

1

Primary sponsor

Full Name

VectorY Therapeutics B.V.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Netherlands

Contract research organisations

Name

Almac Clinical Services Limited

Name

IQVIA Limited

Responsibilities

Multiple vendor responsibilities including clinical trial operations and data services (codes 1,10,11,12,13,4,5,6,7 as listed)

Name

Medidata Solutions Inc.

Responsibilities

URL setup, Coder segment set up, Site cloud set up.

Name

Bioclinica Inc.

Responsibilities

Brain imaging at screening, Week 4 and week 52, Eligibility and safety review.

Name

Primevigilance Limited

Responsibilities

Pharmacovigilance services

Third parties

• {"country":"Netherlands","full_name":"TRICALS Foundation Stichting","duties_or_roles":"Rater Training Services: Rater Training service - Certified Training Services – ALSFRS-R, SVC, HHD, Kings Staging, Electrophysiological Assessments (CMAP/MScan) and TRICALs risk score.","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"URL setup, Coder segment set up, Site cloud set up.","organisation_type":"Non-Pharmaceutical company"}
• {"country":"France","full_name":"Quipment","duties_or_roles":"Supplying equipment to sites","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Iqvia Laboratories Limited","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"France","full_name":"Cerba","duties_or_roles":"Thrombin Time Testing – All Samples; Fructosamine – EU samples; Protein, Total (CSF) – EU Samples","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Brain imaging at screening, Week 4 and week 52, Eligibility and safety review.","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Pharma Services Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Centogene GmbH","duties_or_roles":"Managing genetic testing, whole blood","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Multiple vendor responsibilities including clinical trial operations and data services (codes 1,10,11,12,13,4,5,6,7 as listed)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Quest Diagnostics Nichols Institute Inc.","duties_or_roles":"Protein, Total, CSF (US Samples); Glucose, CSF - All Samples; Lactic Acid, CSF - All Samples","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Bioagilytix Labs LLC","duties_or_roles":"Managing plasma, serum, CSF samples","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"BioAgilytix Europe GmbH","duties_or_roles":"Managing urine, saliva, feces, Whole Blood (K2EDTA), serum, CSF, and PBMCs","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Docs24 Limited","duties_or_roles":"Creating patient source document binder, printing, shipping to sites for all countries.","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Primevigilance Limited","duties_or_roles":"Pharmacovigilance services (sponsor duty code 8)","organisation_type":"Pharmaceutical company"}