SELECT HD

Набор участников завершен

ПОДРОБНЕЕ ОБ ЭТОМ

СПОНСОР

Wave Life Sciences Ltd.

КОЛИЧЕСТВО УЧАСТНИКОВ

36

Исследование является фазой 1/2 и будет изучать безопасность и переносимость участниками нового антисмыслового олигонуклеотида (ASO) на ранней стадии заболевания под названием WVE-003.

WVE-003 — это новая исследовательская молекула, которая пытается уменьшить токсичный белок mHTT (избегая при этом воздействия на здоровый белок хантингтина дикого типа и сохраняя его полезные эффекты в центральной нервной системе).

Дэнлин Сюй представляет обновленную информацию
об испытании SELECT-HD

Возраст, подходящий для исследования:

От 25 до 60 лет

Пол, допущенный к исследованию:

Все

Принимает здоровых добровольцев:

Нет

Критерии включения

  1. Наличие варианта А SNP3 на той же аллели, что и патогенная экспансия триплета CAG
  2. Амбулаторно: пациенты мужского или женского пола в возрасте от ≥25 до ≤60 лет
  3. Клиническая диагностика двигательных признаков БГ, определяемая по Унифицированной шкале оценки болезни Гентингтона (UHDRS) балл диагностической достоверности = 4
  4. Показатели общей функциональной способности по шкале UHDRS ≥9 и ≤13

Критерии исключения

  1. Злокачественная опухоль или прохождение лечения по поводу злокачественной опухоли, за исключением базальноклеточной или плоскоклеточной карциномы кожи, в течение предыдущих 5 лет
  2. Получение любого другого исследуемого препарата, включая исследуемый олигонуклеотид, в течение последнего 1 года или 5 полужизней препарата, в зависимости от того, что больше, за исключением следующих случаев: Получали WVE-120101 или WVE-120102 в течение последних 3 месяцев.
  3. Имплантируемое устройство ЦНС, которое может помешать введению исследуемого препарата через люмбальную пункцию или прохождению магнитно-резонансной томографии
  4. Невозможность пройти МРТ головного мозга (с седацией или без нее)
  5. заболевания костей, позвоночника, кровотечения или другие заболевания, которые подвергают пациента риску травмы или неудачной люмбальной пункции

Страны

Страны

италия

  • TRIAL SITE: Centro Ricerche Cliniche Di Verona
  • Address: Verona, Italy
  • Principal Investigator: Tomasso Bovi, MD

Дания

  • TRIAL SITE:Rigshospitalet
  • Address:Copenhagen, Denmark, 2100
  • Principal Investigator: Lena Hjermind, MD

Франция

  • TRIAL SITE: Hopital Henri Mondor — Hospital
  • Address: Créteil, France, 94010
  • Principal Investigator: Katia Youssov, MD 
  • TRIAL SITE:Institut du Cerveau et de la Moelle Epiniere
  • Address: Paris, France, 75646
  • Principal Investigator: Alexandra Durr, MD, PhD

Нидерланды

  • TRIAL SITE: Leiden University Medical Center
  • Address: Albinusdreef 2, 2333 ZA Leiden, Netherlands
  • Contact: Esther Marks, e.marks@lumc.nl
  • Principal Investigator: Susanne de Bot, MD
  • TRIAL SITE: Maastricht University Medical Center
  • Address:P. Debyelaan 25, 6229 HX Maastricht, Netherlands
  • Principal Investigator: Mayke Oosterloo, MD
  • Contactmayke.oosterloo@mumc.nl

Германия

  • TRIAL SITE: Katholisches Klinikum Bochum gGmbH
  • Address: Bochum, Germany, 44791
  • Principal Investigator: Carsten Saft, MD     
  • TRIAL SITE: George-Huntington-Institut GmbH
  • Address: Muenster, Germany, 48149
  • Principal Investigator: Ralf Reilman, MD  
  • TRIAL SITE: kbo-Isar-Amper-Klinikum Taufkirchen (Vils)
  • Address: Taufkirchen, Germany, 84416
  • Principal Investigator:  Alzbeta Mühlbäck, MD  

Польша

  • TRIAL SITE: Szpital Sw. Wojciecha
  • Address:Gdańsk, Poland, 80-462
  • Principal Investigator: Jaroslaw Slawek, MD     
  • TRIAL SITE: Instytut Psychiatrii I Neurologii
  • Address:Warsaw, Poland, 02-957
  • Principal Investigator: Grzegorz Witkowski, MD, PhD 

Испания

  • TRIAL SITE: Hospital de la Sanata Creu i Sant Pau
  • Address: Barcelona, Spain, 08041
  • Principal Investigator: Jaime Kulisevsky, MD, PhD 
  • TRIAL SITE: Hospital Universitario Ramón y Cajal
  • Address: Madrid, Spain, 28034
  • Principal Investigator: Jose Luis Lopez-Sendon Moreno, MD

ВЕЛИКОБРИТАНИЯ

  • TRIAL SITE: Royal Liverpool University Hospital
  • Address: Liverpool, United Kingdom, L7 8XP
  • Principal Investigator: Richard Rhys Davies, MA BMBCh PhD FRCP 
  • TRIAL SITE: Royal Hospital for Children, Pharmacy Aseptic Unit
  • Address:Glasgow, Glasgow City, United Kingdom, G51 4TF
  • Principal Investigator: Matthew Sheridan 
  • TRIAL SITE: Cardiff University, Schools of Medicine and Biosciences
  • Address: Cardiff, Wales, United Kingdom, CF14 4XW
  • Principal Investigator: Anne Rosser, PhD, MBBChir, MRCP   
  • TRIAL SITE: Royal Victoria Infirmary
  • Address: Newcastle, United Kingdom
  • Principal Investigator: Suresh Komati, MD   
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oxidative seres

an imbalance between unstable molecules called «free radicals» and protective «antioxidants» in your body

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Metabolism & bioenergetics

describe how your body turns food into fuel and uses that energy to live. 

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Small Molecule

a tiny chemical compound, much smaller than big biological structures like proteins, that can easily travel inside our cells to act as medicine (like aspirin or ibuprofen), a building block (like glucose), or a signaling tool in the body, often taken as pills because they’re easy to absorb and distribute

 

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Nucleic acid

(DNA and RNA) are the essential information-carrying molecules in all life, acting like blueprints that store and transmit genetic instructions for building and operating cells, directing everything from growth to protein production, and passing traits from parents to offspring.

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SNP-single nucleotide polymorphisms

a single-letter spelling difference in a gene. SNPs, pronounced ‘snips’, are common and most don’t change the function of the gene.

 
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at risk

You do not know if you carry the genetic mutation for HD gene 

 
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TFC-total functional capacity

A standardized rating scale for function in HD, used to assess capacity to work, handle finances, perform domestic chores and self-care tasks.
Scores range from 0 to 13, with higher scores indicating better functional capacity. 

 
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Double-blinded

 means that neither the participant nor the clinical trial doctor can choose or know the group the participant is in until the trial is over. This approach helps to prevent bias.

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Open label

A trial in which the patient and doctor know what drug is being used. Open label trials are susceptible to bias through placebo effects.

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Gene therapy

a technique that aims to treat or prevent diseases by modifying a person’s genes. It involves introducing, removing, or changing genetic material (DNA or RNA) within a patient’s cells.

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UHDRS- Unified Huntington Disease Rating Scale

A standardized neurological examination that aims to provide a uniform assessment of the clinical features of HD

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CAG repeat

The stretch of DNA at the beginning of the HD gene, which contains the sequence CAG repeated many times, and is abnormally long in people who will develop HD

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Wild-type

the opposite of ‘mutant’. Wild-type huntingtin, for example, is the ‘normal’, ‘healthy’ protein

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Tolerabilty

How well a person can handle a treatment without having serious or uncomfortable side effects.

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Striatum

Part of the brain that  coordinates multiple aspects of cognition, including both motor and action planning, decision-making, motivation, reinforcement, and reward system.

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Randomized allocation

A type of allocation strategy in which participants are assigned to the arms of a clinical trial by chance.

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Radioligand

a radioactive substance that binds to a specific target in the body, allowing visualization of that target’s distribution and activity

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Protein

Protein builds, maintains, and replaces the tissues in your body. The building blocks of life.

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Premanifest / Prodromal

Prior to onset or diagnosis of movement symptoms.

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Placebo

A placebo is a dummy medicine containing no active ingredients. The placebo effect is a psychological effect that causes people to feel better even if they’re taking a pill that doesn’t work.

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PK - Pharmacokinetics

The movement of drugs through the body

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PD - Pharmacodynamics

The body’s biological response to drugs

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PET scan

Positron emission tomography which produces detailed 3-dimensional images of the inside of the body.

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Neuron

Brain cells that store and transmit information

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MRI

Magentic resonance imaging: A technique using powerful magnetic fields to produce detailed images and visualizes the structure of organs, tissues, and bones 

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mHTT

Mutant huntingtin protein. The protein produced by the faulty HD gene.

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Manifest

after HD diagnosis, or when symptoms are already showing

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Longitudinal study

A study where each participant is looked at several times over a time period – unlike a cross-sectional study, where each participant is looked at only once

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HTT

one abbreviation for the gene that causes Huntington’s disease. The same gene is also called HD and IT-15

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fMRI

functional MRI:As with MRI, a technique using powerful magnetic fields  but focusing on brain function by measuring and mapping changes in blood flow, revealing which areas of the brain are active during specific tasks or cognitive processes

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CSF - cerebrospinal fluid

A clear fluid produced by the brain, which surrounds and supports the brain and spinal cord.

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Efficacy

A measure of whether a treatment works or not

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ASO(Antisense oligonucleotides)

A type of gene silencing treatment in which specially designed DNA molecules are used to switch off a gene

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Biomarker

a test of any kind – including blood tests, thinking tests and brain scans – that can measure or predict the progression of a disease like HD. Biomarkers may make clinical trials of new drugs quicker and more reliable

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BDNF

Brain-derived neurotrophic factor: a growth factor that may be able to protect neurons in HD.

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Allele

one of the two copies of a gene

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Plasma

Liquid component of the blood.

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Gene

The basic unit of heredity passed from parent to child. Genes are made up of sequences of DNA and are arranged, one after another, at specific locations on chromosomes in the nucleus of cells.

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Phase

Clinical trial phases are different stages of research that assess the safety and effectiveness of a new medical treatment or intervention in humans.

Each phase has a specific goal and involves a different number of participants. Generally, there are 4 phases (I-IV), with Phase I focusing on safety and dosage, Phase II on efficacy and side effects, Phase III on comparing the new treatment with standard treatments, and Phase IV on long-term safety monitoring.