A Safety and Pharmacokinetics Trial of VO659 in SCA1, SCA3 and HD

NCT05822908 · tracked via the Priya Life Science UK tracker

Sponsor

Vico Therapeutics B. V.

Phase

Phase 1/2

Started

2023-02-14

Last updated

2026-08-19

Condition(s) studied

Spinocerebellar Ataxia Type 1Spinocerebellar Ataxia Type 3Huntington Disease

Investigational drug(s) / intervention(s)

VO659

VO659: VO659 is an antisense oligonucleotide targeting CAG repeats in mRNA transcripts

Study summary

The goal of this first-in-human clinical trial is to assess the safety and tolerability of four doses of a new study drug called VO659 in people with genetic disorders called spinocerebellar ataxia type 1, type 3 or Huntington's disease. Another aim is to determine the concentrations of the study drug in the cerebral spinal fluid and blood after single and multiple doses. Study drug will be administered by lumbar intrathecal bolus injections.

Eligibility

Sex

ALL

Min age

25 Years

Max age

60 Years

Healthy volunteers

Main Inclusion Criteria: * 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 SCA1, SCA3 or HD meeting one of the following criteria: 1. SCA1 and SCA3: mild to moderate disease with a Scale for Assessment and Rating of Ataxia (SARA) score of ≥3 and ≤18 2. HD: 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. For each indication the requirements are: 1. SCA1: ≥41 contiguous, uninterrupted CAG repeats in the ATXN1 gene 2. SCA3: ≥61 repeats in the ATXN3 gene 3. HD: ≥40 CAG repeats in the HTT gene. * Please note there will be additional inclusion criteria Main Exclusion 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, plus either ATXN3 and HTT (for patients with SCA1), ATXN1 and HTT (for participants with SCA3), or ATXN1 and ATXN3 (for participants with HD), in addition to the disease-causing mutation in the ATXN1 (patients with SCA1), ATXN3 (patients with SCA3) or HTT (patients with HD) gene. * 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

Primary outcome measure(s)

Incidence & dose relationships of treatment-related AEs, SAEs, AEs of special interest (AESI), severe events (NCI- CTCAE Grade 3 or higher). — Day 0-253
As measured in each dose group and overall. Unit of measurement: proportion
Vital signs — Day 0-253
temperature in centigrade, heart rate in beats per minute (BPM), systolic and diastolic blood pressure blood pressure, respiratory rate in breaths per minute
Body weight — Day 0-253
In kilograms
Electrocardiogram (ECG) RR interval — Day 0-253
In milliseconds (ms)
Electrocardiogram (ECG) - PR interval — Day 0-253
In milliseconds (ms)
Electrocardiogram (ECG) - QTc interval — Day 0-253
In milliseconds (ms)
Laboratory safety parameters in blood - white blood cell count — Day 0-253
In cells/mL
Laboratory safety parameters in blood - hemoglobin — Day 0-253
In g/dL
Laboratory safety parameters in blood - platelets — Day 0-253
In cells/cL
Laboratory safety parameters in blood - prothrombin time (PT) — Day 0-253
In seconds
Laboratory safety parameters in blood - activated partial thromboplastin clotting time (aPTT) — Day 0-253
In seconds
Laboratory safety parameters in blood - international normalised ratio (INR) — Day 0-253
as a ration
Laboratory safety parameters in blood - blood urea nitrogen — Day 0-253
In mg/dL
Laboratory safety parameters in blood - carbon dioxide — Day 0-253
In mEq/L
Laboratory safety parameters in blood - creatinine — Day 0-253
In mg/dL
Laboratory safety parameters in blood - glucose — Day 0-253
In mg/dL
Laboratory safety parameters in blood - chloride — Day 0-253
In mEq/L
Laboratory safety parameters in blood - potassium — Day 0-253
In mEq/L
Laboratory safety parameters in blood - sodium — Day 0-253
In mEq/L
white blood cell (WBC) count in cerebrospinal fluid (CSF) — Day 0-253
1/µL
Protein levels in cerebrospinal fluid (CSF) — Day 0-253
in g/L
Structural imaging assessment of any new abnormalities — Day 0-253
Structural MRI sequences to assess safety as qualitatively assessed by a trained neuroradiologist (3D T1 weighted, 3D T2weighted-FLAIR and susceptibility-weighted imaging (SWI) sequences)
Percentage of participants with suicidal ideation or behaviour, as assessed by the Columbia suicide severity rating scale (C-SSRS). — Day 0-253
The C-SSRS is a structured tool to assess suicidal ideation and behavior. Four constructs are measured: severity of ideation, intensity of ideation, behavior, and lethality of actual suicide attempts. Binary (yes/no) data are collected for 10 categories, and composite endpoints based on the categories are followed over time to monitor patient safety.

Trial sites (14)

Facility	City	Region	Status
Rigshospitalet	Copenhagen	Denmark	Recruiting
Centre Hospitalier Universitaire dÁngers	Angers	France	Recruiting
CHU Gui de Chauliac Montpellier- Expert Center of Neurogenetic diseases, Department of Neurology	Montpellier	France	Recruiting
Universtiry Hospitals Pitie Salpetriere - Charles foix - Paris	Paris	France	Recruiting
Katholisches Klinikum Bochum	Bochum	Germany	Recruiting
Deutsches Zentrum fur Neurodegenerative Erkrankungen (DZNE)	Bonn	Germany	Recruiting
Universitatsklinikum Essen - Neurologie	Essen	Germany	Recruiting
Universitatsklinikum Tübingen	Tübingen	Germany	Recruiting
Meir Medical Center	Kfar Saba	Israel	Recruiting
Sourmansky Medical Center	Tel Aviv	Israel	Recruiting
Leiden University Medical Center LUMC	Leiden	Netherlands	Active Not Recruiting
Radbout University Medical Centre	Nijmegen	Netherlands	Active Not Recruiting
University College London Hospitals NHS Foundation	London	United Kingdom	Recruiting
John Radcliffe Hospital	Oxford	United Kingdom	Recruiting

Other trials for the same condition

A Study to Investigate the Efficacy, Safety and Tolerability of Votoplam in Participants With Huntington's Disease Recruiting

GENERATION HD2. A Study to Evaluate the Safety, Biomarkers, and Efficacy of Tominersen Compared With Placebo in Participants With Prodromal and Early Manifest Huntington's Disease Active, not recruiting

Safety and Efficacy of AMT-130 in European Adults With Early Manifest Huntington's Disease Active, not recruiting

Pridopidine Phase 3 Study in Huntington's Disease Recruiting

An Extension Study to Evaluate the Long-Term Safety and Efficacy of Votoplam in Participants With Huntington's Disease (HD) Active, not recruiting

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT05822908 on ClinicalTrials.gov ↗ ← All trials in the UK