VO659-CT01

Recruiting

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SPONSOR

Vico Therapeutics B. V.

PARTICIPANTS

21

This is a first-in-human clinical trial to look at the safety, tolerabilty, Pharmacokinetics and Pharmacodynamics of 4 doses of a new study drug called VO659, an ASO. This will be done in people with genetic disorders called spinocerebellar ataxia type 1(SCA), type 3(SCA3) or Huntington’s disease.

Another aim is to determine the concentrations of the study drug in the CSF and blood after single and multiple doses. Study drug will be given by lumbar(spine) injections.

Dose level 1 and 2 will only be done on SCA3. Then level 3-5 will include SCA1 and HD. Before each level the findings will be reviewed by a committee. This is known as a basket study which we have not seen before.

VO659 will target only the mutant allele.

This an open label.

Phase:  1 & 2
Subtype
: Interventional Therapeutic
Primary Purpose: Treatment
Intervention Type: nucleic acid therapy
Primary Intervention: VO659
Mode of Action: HTT Lowering
Duration: 45-58 weeks dependant on which group a participante is in.

Ages Eligible
for Study:

25 Years to 60 Years (Adult )

Sexes Eligible
for Study:

All

Accepts Healthy Volunteers:

No

  • Provide written informed consent (signed and dated). Patients should be assessed for their ability to give informed consent using the Evaluation to Sign Consent tool.
  • Is ≥25 and ≤60 years of age inclusive, of any gender, at the time of signing the informed consent.
  • Have  HD with the following criteria:: early manifest, Stage I disease with a Total Functional Capacity (TFC) Score of ≥11 and ≤13 and a Unified Huntington’s Disease Rating Scale (UHDRS) Diagnostic Confidence Level (DCL) of 4.
  • Have genetically confirmed disease, defined by increased cytosine, adenine, and guanine (CAG) repeat length in the disease-causing allele by direct DNA testing. : ≥36 CAG repeats in the HTT gene.
  • Please note there will be additional inclusion criteria.
  • Have any condition that would prevent participation in trial assessments.
  • Have one or more pathogenic mutation(s) in another polyQ disease gene, i.e., ATXN2, CACNA1A, ATXN7, TBP, AR, and ATN1
  • Have clinical diagnosis of moderate or severe chronic migraines or history of the post-lumbar-puncture headache of moderate or severe intensity requiring hospitalisation or blood patch.
  • Have a brain, spinal or systemic disorder that would interfere with the LP process, CSF circulation, or safety assessments.
  • Have history of bleeding diathesis or coagulopathy, platelet count less than the lower limit of normal unless stable and assessed by the investigator and the Medical Monitor to be not clinically significant.
  • Have uncompensated cardiovascular disorder, any past or present cardiac arrhythmia, QTcF values on screening ECG of >470 ms, familial history of long QT syndrome or sudden unexpected death.
  • Have a history of attempted suicide, suicidal ideation with a plan that required hospital admission and/or change in level of care within 12 months prior to screening.
  • Have medical, psychiatric, or other conditions that, in the judgement of the investigator, may compromise the patient’s ability to understand the patient information sheet, to give informed consent, to comply with all trial requirements, or to complete the trial.
  • Prior treatment with an antisense oligonucleotide (including siRNA).
  • Pregnant or breast-feeding (lactating) women or women who plan to become pregnant or breast-feed during the trial.
  • Unable to undergo and tolerate MRI scans.
  • Please note there will be additional exclusion criteria.

LOCATIONS

COUNTRIES

DENMARK

TRIAL SITE: Kopenhagen, Denmark

Email: info@vicotx.com

FRANCE

TRIAL SITE: Angers, France

Email: info@vicotx.com

TRIAL SITE: Montpellier, France

Email: info@vicotx.com

TRIAL SITE: Paris, France

Email: info@vicotx.com

GERMANY

TRIAL SITE: Bochum, Germany

Email: info@vicotx.com

TRIAL SITE: Bonn, Germany

Email: info@vicotx.com

TRIAL SITE: Essen, Germany

Email: info@vicotx.com

TRIAL SITE: Tübingen, Germany

Email: info@vicotx.com

ISRAEL

TRIAL SITE: Kfar Saba, Israel

Email: info@vicotx.com

TRIAL SITE: Tel Aviv, Israel

Email: info@vicotx.com

NETHERLANDS

TRIAL SITE: Leiden, Netherlands

Email: info@vicotx.com

TRIAL SITE: Nijmegen, Netherlands

Email: info@vicotx.com

UK

TRIAL SITE: London, UK

Email: info@vicotx.com

TRIAL SITE: Oxford, UK

Email: info@vicotx.com

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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.