GEN-PEAK

Een onderzoek naar de farmacokinetiek en farmacodynamiek van RO7234292 (RG6042) in CSF en Plasma, en de veiligheid en verdraagbaarheid na intrathecale toediening bij patiënten met de Ziekte van Huntington

Aanwerving

OVER

SPONSOR

Hoffmann-La Roche

DEELNEMERS

20

The main purpose of GEN-PEAK is to characterise the movement of the drug RG6042 into, through, and out of the cerebrospinal fluid and plasma in addition to reaction to the drug. The study will also look at the time course and recovery profile of cerebrospinal fluid, mutant huntingtin lowering in response to RG6042 treatment after intrathecal  administration of RG6042 to patients with manifest Huntington’s disease.

Estimated Study Completion Date: 24 December, 2021

Leeftijden die in aanmerking komen voor de studie:

25 jaar tot 65 jaar (volwassene, oudere volwassene)

Geslacht komt in aanmerking voor de studie:

Alle

Accepteert gezonde vrijwilligers:

Nee

Insluitingscriteria

  • Duidelijke diagnose van de ziekte van Huntington (HD)
  • Onafhankelijkheidsschaal score van >=70.
  • Genetisch bevestigde ziekte door directe desoxyribonucleïnezuurtest met een in het DNA gevonden sequentie van cytosine-, adenine- en guaninebasen die wordt vertaald in glutamine (CAG) leeftijdsproduct (CAP) score > 400.
  • Het vermogen om de woorden “rood,” “blauw,” en “groen” te lezen in de moedertaal van de patiënt.
  • Het vermogen om zonder hulp van een wandelstok of rollator te lopen en zich dagelijks te verplaatsen zonder rolstoel, zoals beoordeeld tijdens de screening en het basisbezoek.
  • MRI-scans kunnen ondergaan en verdragen.

Uitsluitingscriteria

  • Voorgeschiedenis van poging tot zelfmoord of suïcidale ideatie met plan (d.w.z. actieve suïcidale ideatie) die een ziekenhuisbezoek en/of verandering van zorgniveau vereiste in de 12 maanden voorafgaand aan de screening.
  • Huidige actieve psychose, verwarde toestand, of gewelddadig gedrag.
  • Een ernstige medische aandoening of klinisch significante afwijkingen in het laboratorium, de vitale functies of het ECG tijdens de screening, die naar het oordeel van de onderzoeker een veilige deelname van de patiënt aan en voltooiing van het onderzoek in de weg staan.
  • Klinische diagnose van chronische migraine of voorgeschiedenis van lage druk hoofdpijn na lumbaalpunctie waarvoor ziekenhuisopname of bloedpleister noodzakelijk was.
  • Behandeling met onderzoekstherapie binnen 4 weken voor screening of 5 eliminatiehalfwaardetijden van de onderzoekstherapie, afhankelijk van welke langer is.
  • Gelijktijdige of geplande gelijktijdige deelname aan een interventioneel klinisch onderzoek, met inbegrip van expliciete farmacologische en niet-farmacologische interventies. Observatiestudies zijn aanvaardbaar.
  • Niet in staat of onveilig om een lumbaalpunctie bij de patiënt uit te voeren.
  • Eerdere lumbale chirurgie die naar de mening van de onderzoeker of het chirurgisch team de inbrenging van de IT-katheter of de IT-injectie waarschijnlijk onnodig moeilijk of gevaarlijk maakt.
  • Slechte perifere veneuze toegang.
  • Scoliose of misvorming van de wervelkolom waardoor IT-injectie niet mogelijk is in een poliklinische omgeving.
  • Bestaande intra-axiale of extra-axiale laesies zoals beoordeeld door een centraal afgelezen MRI-scan tijdens de screeningperiode.

COUNTRIES

CONTACT

Hoffmann-La Roche
global-roche-genentech-trials@gene.com

NEDERLAND

PROEFPLAATS: Centre For Human Drug Research

Adres: Leiden, Netherlands, 2333

Aanwerving

UNITED KINGDOM

PROEFPLAATS: Leonard Wolfson Experimental Neurology Centre

Adres: London, United Kingdom, WC1N 3BG

Aanwerving

PROEFPLAATS: Manchester University NHS Foundation Truct (MFT)

Adres: Manchester, United Kingdom, M13 9WL

Aanwerving

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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.