GENERATION HD2

Recrutement

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SPONSOR

Hoffmann-La Roche

PARTICIPANTS

360

Cette étude évalue l’innocuité, les biomarqueurs et les tendances en matière d’efficacité de différents niveaux de dose du médicament expérimental tominersen chez des personnes âgées de 25 à 50 ans présentant des signes prodromiques (signes subtils très précoces de la maladie de Huntington) ou manifestation précoce de la MH. Le tominersen est un médicament expérimental qui a été étudié dans plusieurs essais cliniques depuis 2015, notamment dans une étude de phase III appelée GENERATION HD1 qui a testé deux schémas posologiques différents de tominersen chez des adultes atteints de MH manifeste.

La nouvelle phase II de l’essai GENERATION HD2 est un essai clinique « contrôlé par placebo », ce qui signifie que l’un des groupes recevra une substance sans ingrédients actifs (également appelée « placebo ») ; cette substance ressemble au médicament testé mais ne contient pas de véritable médicament. La comparaison des résultats des différents groupes permet aux chercheurs de savoir si les changements observés sont dus au médicament ou s’ils sont le fruit du hasard.

Il s’agit d’un essai en “double aveugle”, ce qui signifie que ni le participant ni le médecin de l’essai clinique ne peuvent choisir ou connaître le groupe dans lequel le participant se trouve jusqu’à la fin de l’essai. Cette approche permet d’éviter les biais. Toutefois, le médecin de l’essai clinique du participant peut savoir dans quel groupe se trouve le participant, si sa sécurité est menacée.

WEBINAIRE SUR LES MISES A JOUR DE L'ESSAI GENERATION HD2

Âges éligibles pour l'étude

25 à 50 ans.

Sexes éligibles à l'étude

Tous

Accepte les volontaires en bonne santé

Non

CRITÈRES D'INCLUSION

Les personnes peuvent participer à cet essai si elles répondent à certains critères, notamment si elles:

  • sont âgés de 25 à 50 ans (au début de l’essai)
  • Avoir un score CAP (un calcul de recherche basé sur l’âge et le nombre de fois que la section mutée du gène de la maladie se répète – connu sous le nom de nombre CAG) de 400 à 500.
  • ont reçu un diagnostic de maladie de Huntington manifeste précoce ou sont porteurs du gène anormal de la huntingtine et commencent à présenter des signes très précoces et subtils de la maladie de Huntington (connus sous le nom de maladie de Huntington prodromique). Ces signes peuvent n’apparaître que lors d’un examen approfondi par un médecin.
  • Peut tolérer le don de sang, les ponctions lombaires et les IRM.

Avoir une personne qui peut agir en tant que « compagnon d’étude » tout au long de l’essai.

Il est possible que les personnes ne puissent pas participer à cet essai si elles :

  • Ne peut pas marcher sans aide
  • Ne peut pas passer d’IRM
  • Avoir une dérivation ou un cathéter implanté dans le système nerveux central
  • Vous recevez actuellement ou avez déjà reçu certains traitements, y compris ceux pour la MH, qui peuvent affecter les niveaux d’HTT.
  • Vous souffrez de certaines autres affections, notamment de migraines chroniques, de certains problèmes de santé mentale ou de certaines infections

sont enceintes ou allaitent, ou prévoient d’être enceintes pendant ou peu après l’essai clinique

LIEUX

Lieux

L'Autriche
Espagne
  • Facility: Hospital Universitario la Fe; Servicio de Neurologia
  • Address: Avinguda de Fernando Abril Martorell, 106, 46026 València, Valencia
  • Facility: Hospital Universitario de Burgos. Servicio de Neurología
  • Address: Av. Islas Baleares, 3, 09006 Burgos
  • Facility: Hospital Universitario de Burgos. Servicio de Neurología
  • Address: C. de Sant Quintí, 89, 08025 Barcelona
  • Facility: Hospital Universitario de Badajoz; Servicio de Neurología
  • Address: Av. de Elvas, s/n, 06080 Badajoz
  • Facility: Hospital de Cruces; Servicio de Neurologia
  • Address: Cruces Plaza, s/n, 48903 Barakaldo, Bizkaia
  • Facility: Hospital Ramon y Cajal; Servicio de Neurologia
  • Address: M-607, 9, 100, 28034 Madrid

Active, Not Recruiting

  • Facility: Hospital Universitario Virgen Macarena; Servicio de Neurologia
  • Address: Av. Dr. Fedriani, 3, 41009 Sevilla

Active, Not Recruiting

Danemark
  • Facility: Rigshospitalet, Hukommelsesklinikken
  • Address: Koebenhavn Oe, Denmark, 2100
france
  • Facility: CHU Angers Cedex 9, Neurologie.
  • Address: Rue Larrey 2, France, 49933
  • Contact: Christophe Verny
  • Facility: Hopital Henri Mondor, Service de Neurologie
  • Address: 51 Avenue de Lattre de Tassigny, Creteil, 94010 France.
  • Contact: Anne-Catherine Bachoud-Lévi
  • Facility: Hôpital de Hautepierre – Hôpitaux Universitaires de Strasbourg
  • Address: Strasbourg, 1 Avenue Moliere, 67200 France.
  • Contact: Christine Tranchant
  • Facility: Roger Salengro Hospital
  • Address: Lille, Rue du Prof. Laine, 59037 France.
  • Contact: Clémence Simonin 
  • Facility: University Hospital Center Saint Eloi Hospital
  • Address: Montpellier, 80 Avenue Augustin Fliche, 34295 France
  • Contact: Cécilia Marelli
  • Facility: Marseille University Hospital Timone
  • Address: Marseille, Rue saint pierre, 13385 France.
  • Contact: Jean-Philippe Azulay
  • Facility: Hospital Center University De Bordeaux
  • Address: Bordeaux, Place Amelie Raba-Leon, 33076 France.
  • Contact: Cyril Goizet
  • Facility: CHU Toulouse, Hôpital Purpan
  • Address: Place Du Docteur Baylac, 31059 France.
  • Contact: Jérémie Pariente
Allemagne
  • Facility: Charité – Universitätsmed. Berlin, Klinik für Psychiatrie und Psychotherapie; Abt. Neuropsychiatrie.
  • Address: Bonhoefferweg 3, 10117 Berlin, Germany
  • Facility: St. Josef-Hospital, Neurologische Klinik der Ruhr-Uni; Huntington-Center NRW, Abt. Neurodegeneration Bochum.
  • Address: St. Josef-Hospital, Gudrunstraße 56, 44791 Bochum, Germany
  • Facility: German Center for Neurodegenerative Diseases (DZNE)
  • Address: Bonn, Germany, 53127
  • Facility: Universitätsklinikum Erlangen, Abteilung Molekulare Neurologie
  • Address: Erlangen, Germany, 91054
  • Facility: Universitätsklinikum Schleswig-Holstein / Campus Lübeck; Zentrum für Seltene Erkrankungen
  • Address: Lübeck, Germany, 23538
  • Facility: Universitätsklinikum Ulm; Klinik für Neurologie
  • Address: Ulm, Germany, 89081
  • Facility: Uniklinik RWTH Aashen, Klinik für Neurologie
  • Address: Aachen Germany 52074
italie
  • Facility: Ospedale Bellaria; Istituto delle Scienze Neurologiche
  • Address: Bologna, Emilia-Romagna, Italy, 40139
  • Facility: Fondazione IRCCS Istituto Neurologico Carlo Besta; U.O.C. Genetica Medica-Neurogenetica
  • Address: Milano, Lombardia, Italy, 20133
  • Facility: Azienda Ospedaliera Sant’Andrea UOC Neurologia
  • Address: Roma, Lazio, Italy 00189
Pologne
  • Facility: Szpital Sw. Wojciecha; Oddzial Neurologiczny
  • Address: Gdansk, Poland, 80-462
  • Facility: Krakowska Akademia Neurologii Sp z o.o. Centrum Neurologii K Krakow, Poland, 31-505
  • Address: Krakow, Poland, 31-505
  • Facility: Instytut Psychiatrii i Neurologii
  • Address: Warszawa, Poland, 02-957
portugal
  • Facility: CNS – Campus Neurológico
  • Address: Torres Vedras, Portugal, 2560-280
  • Facility: Hospital de Santa Maria – Serviço de Neurologia, Lisboa, Portugal. Contact: Leonor Correia Guedes
  • Address: Av. Prof. Egas Moniz MB, 1649-028 Lisboa, Portugal
  • Contact: Leonor Correia Guedes
Suisse
  • Facility: Neurozentrum Siloah
  • Address: Gümligen, Switzerland, 3073
  • Facility: Universitätsspital Basel Neurologie
  • Address: Basel Switzerland 4031
Royaume-Uni
  • Facility: Chapel Allerton Hospital; Clinical Genetics Leeds
  • Address: United Kingdom, LS7 4SA
  • Facility: UCL Hospital NHS Trust
  • Address: London, United Kingdom, NW1 2PG
  • Facility: University Hospitals Birmingham NHS Foundation Trust
  • Address: Birmingham, United Kingdom, B152TH
  • Facility: Addenbrookes Hospital
  • Address: Cambridge United Kingdom CB20QQ
  • Facility: John Radcliffe Hospital Neurosciences
  • Address: Chinnor, United Kingdom, OX39DU
  • Facility: Southampton University Hospitals, NHS Trust
  • Address: Southampton, United Kingdom, SO166YD
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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. 

 
 
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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.