Studie hodnotí bezpečnost a snášenlivost přípravku VTx-002 u účastníků s ALS (ALS)
Fáze 1/2 zkoumání nového experimentálního režimu u amyotrofické laterální sklerózy (Pioneer-ALS): Otevřená, nekontrolovaná, multicentrická studie k posouzení bezpečnosti a snášenlivosti dvou dávek VTx-002
PIONEER-ALS is a Phase 1/2, multicenter, 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.
Přehled studie
Postavení
Postavení
Podmínky
Podmínky
Intervence / Léčba
Intervence / Léčba
Detailní popis
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.
Typ studie
Typ studie
Zápis (Odhadovaný)
Zápis
Fáze
Fáze
- Fáze 2
- Fáze 1
Kontakty a umístění
Studijní kontakt
Studijní kontakt
- Jméno: Dr Olga Uspenskaya Chief medical Officer, VectorY Therapeutics, M.D; PhD
- Telefonní číslo: patients@vectorytx.com
- E-mail: patients@vectorytx.com
Studijní místa
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Leuven, Belgie
- Nábor
- UZ Leuven
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Kontakt:
- Evi Parente Study Coordinator
- Telefonní číslo: + 32 1638668
- E-mail: evi.parente@uzleuven.be
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Kontakt:
- Ann Dhondt Study Coordinator
- Telefonní číslo: + 32 16347577
- E-mail: ann.dhondt@uzleuven.be
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Vrchní vyšetřovatel:
- Dr Philip Van Damme, Doctor of Medicine
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Utrecht, Holandsko
- Nábor
- UMC Utrecht
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Kontakt:
- Prof Leonard Van Den Berg, Doctor of Medicine
- Telefonní číslo: +31 887555555
- E-mail: l.h.vandenberg@umcutrecht.nl
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Vrchní vyšetřovatel:
- Prof Leonard Van Den Berg, Doctor of Medicine
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Sheffield, Spojené království, S10 2JF
- Nábor
- Royal Hallamshire Hospital
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Kontakt:
- Dr Chris McDermott, Doctor of medicine
- Telefonní číslo: +44 114 226 1049
- E-mail: c.j.mcdermott@sheffield.ac.uk
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Arizona
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Phoenix, Arizona, Spojené státy, 85013
- Zatím nenabíráme
- St Joseph's Hospital and medical Center - Barrow Neurological Institute
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Vrchní vyšetřovatel:
- Dr Shafeeq Ladha, Doctor of Medicine
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Kontakt:
- Dr S Ladha, Doctor of Medicine
- Telefonní číslo: (602) 406-6262
- E-mail: fulton.research@commonspirit.org
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California
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San Diego, California, Spojené státy, 92121
- Nábor
- University of California San Diego Medical Center
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Kontakt:
- Dr John Ravits, Doctor of Medicine
- Telefonní číslo: (858) 246-1154
- E-mail: jravits@health.ucsd.edu
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Vrchní vyšetřovatel:
- Dr John Ravits, Doctor of Medicine
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Florida
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Jacksonville, Florida, Spojené státy, 32224
- Nábor
- Mayo Clinic in Florida
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Kontakt:
- Dr Bjorn Oskarsson, Doctor of Medicine
- Telefonní číslo: (904) 953-0407
- E-mail: oskarsson.bjorn@mayo.edu
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Vrchní vyšetřovatel:
- Dr Bjorn Oskarsson, Doctor of Medicine
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Massachusetts
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Boston, Massachusetts, Spojené státy, 02114
- Nábor
- Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital
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Vrchní vyšetřovatel:
- Dr Doreen Ho, Doctor of Medicine
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Kontakt:
- Winifred Asigri Study Coordinator
- Telefonní číslo: (617) 724-5659
- E-mail: pioneeralshealey@mgb.org
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New York
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New York, New York, Spojené státy, 10032
- Zatím nenabíráme
- The Eleanor & Lou Gehrig ALS Center
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Vrchní vyšetřovatel:
- Dr Neil Schneider, Doctor of Medicine
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Kontakt:
- The Eleanor & Lou Gehrig ALS Center
- Telefonní číslo: (212) 305-6788
- E-mail: alsresearch@cumc.columbia.edu
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Pennsylvania
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Philadelphia, Pennsylvania, Spojené státy, 19104
- Nábor
- University of Pennsylvania
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Vrchní vyšetřovatel:
- Dr Colin Quinn, Doctor of Medicine
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Kontakt:
- Spriha Thapa Study Coordinator
- Telefonní číslo: 267-610-8822
- E-mail: Spriha.Thapa@pennmedicine.upenn.edu
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Kritéria účasti
Kritéria způsobilosti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
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
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Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Nerandomizované
- Intervenční model: Sekvenční přiřazení
- Maskování: Žádné (otevřený štítek)
Počet zbraní
Zbraně a zásahy
Skupina účastníků / ArmSkupina účastníků / Arm |
Intervence / LéčbaIntervence / Léčba |
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Experimentální: Gene Therapy Group 1: Dose 1 (Low Dose)
Gene Therapy: VTx-002 18 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 |
An investigational gene therapy targeting a specific protein. To reduce the risk of reactions caused by the study treatment, steroid medicines will be given in advance.
Ostatní jména:
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Experimentální: Gene Therapy Group 2: Dose 2 (High Dose)
Gene Therapy: VTx-002 18 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 |
An investigational gene therapy targeting a specific protein. To reduce the risk of reactions caused by the study treatment, steroid medicines will be given in advance.
Ostatní jména:
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Co je měření studie?
Primární výstupní opatření
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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The number of participants with treatment related adverse events (AEs) and Serious Adverse Events (SAEs)
Časové okno: Over 5 years
|
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)
Časové okno: Over 5 years
|
Assessed by reviewing laboratory values |
Over 5 years
|
|
The number of participants with treatment related adverse events (AEs) and Serious Adverse Events (SAEs)
Časové okno: Over 5 years
|
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)
Časové okno: over 5 years
|
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
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The number of participants with treatment related adverse events (AEs) and Serious Adverse Events (SAEs)
Časové okno: Over 5 years
|
Assessed by reviewing cellular responses by analyzing blood samples. |
Over 5 years
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The number of participants with treatment related adverse events (AEs) and Serious Adverse Events (SAEs)
Časové okno: Over 5 years
|
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. |
Over 5 years
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The number of participants with treatment related adverse events (AEs) and Serious Adverse Events (SAEs)
Časové okno: At month 6 and month 12
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Assessed by performing 4 formal interim analyses
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At month 6 and month 12
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Sekundární výstupní opatření
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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To assess whether VTx-002 works to prevent the progression of ALS and what dose can be used for future clinical studies.
Časové okno: At month 6 and month 12
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Changes certain blood values |
At month 6 and month 12
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To assess whether VTx-002 works to prevent the progression of ALS and what dose can be used for future clinical studies.
Časové okno: over 12 months
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Time to assisted permanent ventilation or death |
over 12 months
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To assess whether VTx-002 works to prevent the progression of ALS and what dose can be used for future clinical studies.
Časové okno: Over 5 years
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Immune responses assessed by analyzing blood samples |
Over 5 years
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To assess whether VTx-002 works to prevent the progression of ALS and what dose can be used for future clinical studies.
Časové okno: At month 6 and month 12
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Change in Slow Vital Capacity |
At month 6 and month 12
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To assess whether VTx-002 works to prevent the progression of ALS and what dose can be used for future clinical studies.
Časové okno: At month 6 and month 12
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Changes in CSF values |
At month 6 and month 12
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To assess whether VTx-002 works to prevent the progression of ALS and what dose can be used for future clinical studies.
Časové okno: At month 6 and month 12 *ALSFRS-R is a scale used to monitor disease progression. The 12 questions. Questions are scored from 0 to 4, with a maximum score of 48 indicating full function and a minimum score of 0 indicating significant impairment.
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Change in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) |
At month 6 and month 12 *ALSFRS-R is a scale used to monitor disease progression. The 12 questions. Questions are scored from 0 to 4, with a maximum score of 48 indicating full function and a minimum score of 0 indicating significant impairment.
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Další výstupní opatření
Další výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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To assess changes in biomarkers
Časové okno: Over 5 years
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Analysis of blood samples to assess viral shedding |
Over 5 years
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To assess changes in muscle strength assessments from baseline.
Časové okno: Measured at month 6 and month 12
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Change in muscle strength measured by Hand-held Dynamometry |
Measured at month 6 and month 12
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To assess disease severity and improvement
Časové okno: over 12 months
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Disease severity and improvement measured using the Clinical Global Impression (CGI) scales for Severity (CGI-S) and Improvement (CGI-I). The CGI scales each use a seven-point scale where 1 indicates less severe (CGI-S) or most improved (CGI-I) and 7 indicates more severe illness (CGI-S) or worsening of condition (CGI-I) |
over 12 months
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To assess immunogenicity of VTx002
Časové okno: Over 5 years
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Assessed by the review of the immunogenicity to the capsid and transgene by analyzing blood samples. |
Over 5 years
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To assess changes Health Related Quality of Life
Časové okno: Measured at month 6 and month 12
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Change in Health Related Quality of Life measured using the EQ5D-L questionnaire. *The EQ5D-L is a self-completed questionnaire assessing five core dimensions (Mobility, Self-care, Usual Activities, Pain/Discomfort, Anxiety/Depression). It is scored by combining patient responses across the five dimensions and then converting to a single utility score whereby 1.0 indicates perfect health and 0 indicates death |
Measured at month 6 and month 12
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To assess changes Health Related Quality of Life
Časové okno: Measured at month 6 and month 12
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Change in Health Related Quality of Life measured using the ALSAQ-5 questionnaire. *The ALSAQ-5 is a brief, 5-item questionnaire used to measure the impact of Amyotrophic Lateral Sclerosis on a patient's quality of life. Five key areas are rated for difficulties and converted to a total score from 0 (worst) to 100 (best) |
Measured at month 6 and month 12
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Spolupracovníci a vyšetřovatelé
Sponzor
Sponzor
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Začátek studia
Primární dokončení (Odhadovaný)
Primární dokončení
Dokončení studie (Odhadovaný)
Dokončení studie
Termíny zápisu do studia
První předloženo
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
První zveřejněno
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Poslední zveřejněná aktualizace
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Onemocnění centrálního nervového systému
- Nemoci nervového systému
- Neuromuskulární onemocnění
- Metabolické choroby
- Neurodegenerativní onemocnění
- Nemoci míchy
- Proteinopatie TDP-43
- Nedostatky proteostázy
- Nemoc motorických neuronů
- Nutriční a metabolické nemoci
- Amyotrofní laterální skleróza
- Polycyklické sloučeniny
- Těhotenství
- Těhotenství
- Steroidy
- Sloučeniny roztaveného kruhu
- Těhotenství
- Těhotenství
- Prednison
- Prednisolon
Další identifikační čísla studie
Další identifikační čísla studie
- VTx-002-01-001
- 2025-522697-37-00 (Ctis)
- PIONEER-ALS (Jiný identifikátor: VectoryTherapeutics)
- 2025 (Grant/smlouva NIH USA)
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
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