Study is to Assess the Safety and Tolerability of VTx-002 in Participants With ALS

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Генная терапия VTx-002
  An investigational gene therapy targeting a specific protein.
• Препарат Preventative (Prophylactic) Medication - Corticosteroids: Methylprednisolone
  To reduce the risk of reactions caused by the study treatment, steroid medicines will be given in advance.

Первичные конечные точки

• The number of participants with treatment related adverse events (AEs) and Serious Adverse Events (SAEs) [Срок оценки: Over 5 years]
• The number of participants with treatment related adverse events (AEs) and Serious Adverse Events (SAEs) [Срок оценки: Over 5 years]
• The number of participants with treatment related adverse events (AEs) and Serious Adverse Events (SAEs) [Срок оценки: Over 5 years]
• The number of participants with treatment related adverse events (AEs) and Serious Adverse Events (SAEs) [Срок оценки: over 5 years]
• The number of participants with treatment related adverse events (AEs) and Serious Adverse Events (SAEs) [Срок оценки: Over 5 years]
• The number of participants with treatment related adverse events (AEs) and Serious Adverse Events (SAEs) [Срок оценки: Over 5 years]
• The number of participants with treatment related adverse events (AEs) and Serious Adverse Events (SAEs) [Срок оценки: At month 6 and month 12]

Вторичные конечные точки (6)

• To assess whether VTx-002 works to prevent the progression of ALS and what dose can be used for future clinical studies. [Срок оценки: 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. [Срок оценки: over 12 months]
• To assess whether VTx-002 works to prevent the progression of ALS and what dose can be used for future clinical studies. [Срок оценки: Over 5 years]
• To assess whether VTx-002 works to prevent the progression of ALS and what dose can be used for future clinical studies. [Срок оценки: 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. [Срок оценки: 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. [Срок оценки: 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.]

Критерии участия

Критерии включения

• 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)

Критерии исключения

• 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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Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 7 центров

• St Joseph's Hospital and medical Center - Barrow Neurological Institute — Phoenix
• University of California San Diego Medical Center — San Diego
• Mayo Clinic in Florida — Jacksonville
• University of Miami School of Science — Miami
• Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital — Boston
• Herbert Irving Comprehensive Cancer Center — New York
• University of Pennsylvania — Philadelphia

Великобритания · 2 центра

• Kings College Hospital — London
• Royal Hallamshire Hospital — Sheffield

Бельгия · 1 центр

• UZ Leuven — Leuven

Нидерланды · 1 центр

• UMC Utrecht — Utrecht

Идентификаторы

NCT: NCT07287397 · VTx-002-01-001 · 2025-522697-37-00 · PIONEER-ALS

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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