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CHDI Foundation, Inc.

PARTICIPANTS

27

Offcial title: First in Human Adaptive Study to Investigate the Kinetic Properties of the Novel PET Radioligand [11C]CHDI-00491009 and Its Suitability for Quantification of Aggregated Mutant Huntingtin in the Brains of People With Huntington’s Disease

This study is the first time a new imaging tool is being tested in people. It looks at a special tracer (a small, detectable substance) that can be seen on a brain scan and is designed to attach to the harmful protein linked to Huntington’s disease (HD). The goal is to see if this scan can reliably detect and measure that protein in the brain.

The study is done in three small groups:

  • Group 1:initial tracer validation. 3 healthy controls(HC)  are scanned to make sure the tracer works safely and properly.
  • Group 2: target validation and test-retest variability. 6 HD-ISS Stage 3 participants and 6 age and biological sex-matched HCs are scanned to check if the tracer can clearly detect the disease and give consistent results.
  • Group 3: target sensitivity 6 HD-ISS Stage 2 participants and 6 age and biological sex-matched HCs  are scanned to see how sensitive the tracer is at detecting changes earlier in the disease.

After each group, researchers review the results before moving on.

Besides the brain scans, the study also looks at other biological markers. Blood samples will be taken to study changes in the gene linked to HD. Participants with HD may also choose to give a sample of cerebrospinal fluid (the fluid around the brain and spinal cord) to measure levels of the disease-related protein.

This an open label.

Phase: early Phase 1
Subtype: Interventional Biomarker
Primary Purpose: Other
Primary Intervention: Radioligand [11C]CHDI-00491009

Ages Eligible
for Study:

18 – 64  years old

Sexes Eligible
for Study:

All

Accepts Healthy Volunteers:

Yes

PwHD HD-ISS Stages 2 and 3 and HC participants who:

  1. Are female or male adults, age 18-64 years old, inclusive.
  2. Have body mass index (BMI) between 19 and 35, inclusive.
  3. Have capacity to give full informed consent in writing and have read and signed the informed consent form (ICF).
  4. Are able to comply with study procedures, including fasting and blood sampling.
  5. Are able and willing to travel to the imaging center in Leuven, Belgium.
  6. Are willing to comply with the use of adequate contraceptive measures.

    HD-ISS Stage 2 participants who:

  7. Have a huntingtin gene CAG expansion between 40 and 50, inclusive; and
  8. Are classified within HD-ISS Stage 2 per the HD-ISS criteria using HD-ISS Modified Stage calculator.
  9. Have a PIN score of 0.47 to 1.84 [prognostic index normed for HD (PIN) where PIN = (PIHD – 883)/1044 where PIHD = 51 x TMS + (-34) x SDMT + 7 x Age x (CAG – 34) (TMS is the UHDRS Total Motor Score, and SDMT is the UHDRS Symbol Digit Modalities Test)].

HD-ISS Stage 2 participants who:

7. Have a huntingtin gene CAG expansion between 40 and 50, inclusive; and 8. Are classified within HD-ISS Stage 2 per the HD-ISS criteria using HD-ISS Modified Stage calculator.

9. Have a PIN score of 0.47 to 1.84 [prognostic index normed for HD (PIN) where PIN = (PIHD – 883)/1044 where PIHD = 51 x TMS + (-34) x SDMT + 7 x Age x (CAG – 34) (TMS is the UHDRS Total Motor Score, and SDMT is the UHDRS Symbol Digit Modalities Test)].

HC participants who:

13. Have no known family history of HD; or 14. Have a known family history of HD and have been tested for the huntingtin gene CAG expansion and are not at genetic risk for HD (CAG < 36).

15. Age match (+/- 5 years) and biological sex match to each HD participant in Cohort 2 and Cohort 3 (except for Cohort 1, no matching).

PwHD HD-ISS Stages 2 and 3 and HC participants who:

  1. Are currently participating in, or are less than 30 days after completing participation in, other therapeutic or imaging studies.
  2. Have previously participated in a PET imaging study in the past 12 months that, cumulatively with the current study, will exceed annual regulatory limits for radiation exposure.
  3. Have any disease, condition, or concomitant medication that significantly compromises the function of the body systems and that, in the opinion of the Investigator, might interfere with the conduct of the study or its interpretation.
  4. Are pregnant and breastfeeding females.
  5. Have concomitant use of antiplatelet or anticoagulant therapy (inclusive of acetylsalicylic acid).
  6. Have a bleeding disorder.
  7. Have a needle phobia.
  8. Have any metal objects present in the body that are incompatible with MRI.
  9. Have metal objects present in the body that are compatible with MRI and are located in the head or neck.
  10. Have any clinically significant results on safety laboratory tests that, in the opinion of the Investigator, would either put the participant at risk or interfere with the conduct of the study or interpretation of data. These tests include, but are not limited to:

    • a. positive results for HBsAg, HepC, HIV-1 or HIV-2 (will also be reported as required by local/national regulations),
    • b. clinically significant, abnormal results for safety laboratory tests.

    PwHD participants who:

  11. If they are using any antidepressant, psychoactive, psychotropic or other medications or nutraceuticals used to treat HD, the use of inappropriate (e.g., non-therapeutically high) or unstable dose within 30 days prior to participation.

    HC participants who:

  12. Have a family history of HD and have not been tested for the huntingtin gene (CAG) expansion.
Ages Eligible for Study
18 Years to 64 Years (Adult )
Sexes Eligible for Study
All
Accepts Healthy Volunteers
Yes

LOCATION

BELGIUM

TRIAL SITE:
UZ LEUVEN

Address: Leuven, Belgium

Universitaire Ziekenhuizen Leuven/ UZ Leuven/ UZL

Contact : Wim Vandenberghe, MD, PhD
Email:wim.vandenberghe@uzleuven.be
 
Contact : Koen Van Laere, MD, PhD, DSc
Email:koen.vanlaere@uzleuven.be

 

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siRNA

A way of silencing genes using specially designed molecules of RNA – like DNA but made of only a single strand – that target the message molecules in cells and tell them not to make a certain protein

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phenoptype

Phenotype refers to an individual’s observable traits, such as height, eye color and blood type. A person’s phenotype is determined by both their genomic makeup (genotype) and environmental factors.

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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.