First-in-Human Study of ALN-SNCA in Adult Participants With Early Parkinson's Disease (PD)

Официальное название

First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Doses of Intrathecally Administered ALN-SNCA in Participants With Early Parkinson's Disease

Обзор

This study is researching an experimental drug called ALN-SNCA (called "study drug"). The study is focused on people with early Parkinson's disease, a disorder of the nervous system that affects movement. Parkinson's disease is caused by a gradual loss of nerve cells in the brain, especially those due to the harmful build-up of a protein called α-synuclein. The aim of the study is to see if the study drug is safe and tolerated well enough to continue testing it in future studies and what side effects may happen from taking the study drug. The study is looking at several other research questions, including: * Whether the study drug can lower the level of α-synuclein protein in the Cerebrospinal Fluid (also referred to as "CSF", the fluid that surrounds the brain and spinal cord) * How much study drug is in the blood, urine, and CSF at different times * Compatible research to better understand the study drug (ALN-SNCA) and Parkinson's disease, including (but not limited to), whether the study drug can slow down the progression of Parkinson's disease symptoms

Вмешательства

• Препарат ALN-SNCA
  Administered per the protocol
• Препарат Placebo
  Administered per the protocol

Первичные конечные точки

• Occurrence of Treatment-Emergent Adverse Events (TEAEs) [Срок оценки: Through Week 80]
• Severity of TEAEs [Срок оценки: Through Week 80]

Вторичные конечные точки (8)

• Concentration of alpha (a)-synuclein protein in CSF [Срок оценки: Through Week 48]
• Change from baseline in concentration of a-synuclein protein in CSF [Срок оценки: Through Week 48]
• Concentration of ALN-SNCA in plasma [Срок оценки: Through Week 48]
• Concentration of major metabolites in plasma [Срок оценки: Through Week 48]
• Concentration of ALN-SNCA in CSF [Срок оценки: Through Week 48]
• Concentration of major metabolites in CSF [Срок оценки: Through Week 48]
• Fraction [fc] of ALN-SNCA excreted in urine [Срок оценки: Over 24 hours]
• Fc of major metabolites excreted in urine [Срок оценки: Over 24 hours]

Критерии участия

Критерии включения

• Diagnosis of Parkinson's disease according to the Movement Disorder Society (MDS) criteria, as assessed by the investigator, with bradykinesia plus at least one of the other cardinal signs of Parkinson's disease (resting tremor, rigidity), without any other known or suspected cause of Parkinsonism
• A diagnosis of Parkinson's disease for 4 years or less at the screening visit
• Participant must meet one of the following criteria:

• Currently not receiving any standard-of-care (SoC) therapy for Parkinson's disease, has not been on oral dopaminergic therapy (ie, levodopa, dopamine agonists, or Monoamine Oxidase B \[MAO-B\] inhibitors) prior to dosing, and is not anticipated to require SoC therapy for Parkinson's disease within approximately 6 months following dosing, or
• Has been on a stable regimen of oral dopaminergic therapy for at least 3 months prior to dosing and is not anticipated to require dose adjustments within approximately 6 months following dosing
• BMI ≤35 kg/m\^2 at time of screening visit

Критерии исключения

• Medical history indicating a Parkinsonian syndrome other than Parkinson's disease, as defined in the protocol
• Clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, psychiatric or neurological disease (excluding Parkinson's disease) that, as assessed by the investigator, may confound the results of the study or pose an additional risk to the participant during study participation
• Medical history of brain or spinal disease/injury that would interfere with the Lumbar Puncture (LP) procedure or CSF circulation, as defined in the protocol
• Any contraindications to undergo a brain Magnetic Resonance Imaging (MRI)
• An established allergy or intolerance to lidocaine anesthetic, as defined in the protocol
• History of intolerance to Intrathecal (IT) injection(s)
• Current history of bleeding diatheses that would increase risk of bleeding upon LP
• Has undergone gene therapy, cell therapy or surgical treatment, including deep brain stimulation, for Parkinson's disease

NOTE: Other Protocol-defined Inclusion/Exclusion Criteria Apply

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Канада · 1 центр

• Montreal Neurological Institute and Hospital — Montreal

Нидерланды · 1 центр

• Center for Human Drug Research — Leiden

Идентификаторы

NCT: NCT07216066 · ALN-SNCA-PD-2482 · 2025-521431-37-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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