A Phase 1/2 interventional study of VO659 in Spinocerebellar Ataxia Type 1, Spinocerebellar Ataxia Type 3 and Huntington Disease, sponsored by Vico Therapeutics B. V.. Recruiting at 14 sites in 6 countries. Open to participants aged 25 Years to 60 Years. Per ClinicalTrials.gov, last updated 2026-08-19.
Sponsored by Vico Therapeutics B. V. · Phase 1/2, Interventional, and Treatment
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.
Spinocerebellar ataxia types 1 and 3 (SCA1 and SCA3), as well as Huntington's disease (HD) are severely debilitating, monogenic, neurodegenerative diseases that presently have no treatments to slow or stop clinical progression. Preclinical data suggest that VO659 may be a disease-modifying therapy in these disorders through its binding to the expansion of CAG repeats in the RNA transcripts of the causative genes, thus interfering with RNA translation and reducing the intracellular level of the harmful mutant proteins.
The present trial is the first-in-human (FiH) evaluation of VO659. This is an open-label, multiple ascending dose, multi-centre phase 1/2a trial investigate the safety, tolerability and pharmacokinetics and explore the pharmacodynamics of intrathecally administered study drug VO659.
The trial population comprises generally ambulatory participants with mild to moderate SCA1 or SCA3, or early manifest HD. Participants are assigned to dose-ascending treatment cohorts based on the order of enrolment. Dose-escalation is planned in up to five dose levels. Dose-level cohorts one and two will comprise participants with SCA3 only, and from dose-level cohorts three onwards participants with SCA1, SCA3 and HD will be enrolled.
The total duration of trial participation for each participant in Dose-level Cohorts 1-3 is up to approximately 45 weeks, consisting of a screening period of up to 6 weeks, a 14-week dosing period, and a 25-week post-dosing period.
The total duration of trial participation for each participant in Dose-level Cohort 4 is up to approximately 58 weeks, consisting of a screening period of up to 7 weeks, a 26-week dosing period, and a 25-week post dosing period. The total duration of trial participation for each participant in Dose-level Cohort 5 is up to approximately 58 weeks, consisting of a screening period of up to 7 weeks, a single dosing followed by a 51-week period of non-dosing, observational visits (split into a 26-week 'dosing period' and a 25-week 'post-dosing period' for consistency in the SoA with Dose-level Cohort 4).
33 studies on the registry are indexed under Machado-Joseph Disease; 5 are open to participants now.
This study's planned enrollment of 68 is above the median of 23 across 21 interventional studies indexed under Machado-Joseph Disease.
Browse Machado-Joseph Disease studies →This is the only study on the registry with Vico Therapeutics B. V. as lead sponsor.
Compared within Machado-Joseph Disease, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Spinocerebellar Ataxias. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Main Inclusion Criteria:
Have SCA1, SCA3 or HD meeting one of the following criteria:
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:
Main Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A dose of 10 mg of the trial IMP VO659 will be administered intrathecally four times on Day 1, Day 29, Day 57 and Day 85 within the planned dosing blocks. The total duration of trial participation for each participant is up to approximately 42 weeks, consisting of a screening period of up to 6 weeks, a 13-week dosing period and a 23-week post-dosing period.
Drug: VO659
A dose of 20 mg of the trial IMP VO659 will be administered intrathecally four times on Day 1, Day 29, Day 57 and Day 85 within the planned dosing blocks. The total duration of trial participation for each participant is up to approximately 42 weeks, consisting of a screening period of up to 6 weeks, a 13-week dosing period and a 23-week post-dosing period.
Drug: VO659
A dose of 40 mg of the trial IMP VO659 will be administered intrathecally four times on Day 1, Day 29, Day 57 and Day 85 within the planned dosing blocks. The total duration of trial participation for each participant is up to approximately 42 weeks, consisting of a screening period of up to 6 weeks, a 13-week dosing period and a 23-week post-dosing period.
Drug: VO659
A dose of 20 or 40 mg of the trial IMP VO659 will be randomly assigned and will be administered intrathecally. For Dose-level Cohort 4, the dosing period consists of 3 dosing blocks for participants in the 3x20 mg treatment arm (Days -1 to 3; Days 84-87; and Days 168-171) and 2 dosing blocks for participants in the 2x40 mg treatment arm (Days -1 to 3; and Days 168-171). The total duration of trial participation for each participant in Dose-level Cohort 4 is up to approximately 58 weeks, consisting of a screening period of up to 7 weeks, a 26-week dosing period, and a 25-week post dosing period.
Drug: VO659
A dose of 60 mg of the trial IMP VO659 will be administered intrathecally once on day 1. The total duration of trial participation for each participant in Dose-level Cohort 5 is up to approximately 58 weeks, consisting of a screening period of up to 7 weeks, a single dosing followed by a 51-week period of non-dosing, observational visits.
Drug: VO659
VO659 is an antisense oligonucleotide targeting CAG repeats in mRNA transcripts
Incidence & dose relationships of treatment-related AEs, SAEs, AEs of special interest (AESI), severe events (NCI- CTCAE Grade 3 or higher).
As measured in each dose group and overall. Unit of measurement: proportion
Time frame: Day 0-253
Vital signs
temperature in centigrade, heart rate in beats per minute (BPM), systolic and diastolic blood pressure blood pressure, respiratory rate in breaths per minute
Time frame: Day 0-253
Body weight
In kilograms
Time frame: Day 0-253
Electrocardiogram (ECG) RR interval
In milliseconds (ms)
Time frame: Day 0-253
Electrocardiogram (ECG) - PR interval
In milliseconds (ms)
Time frame: Day 0-253
Electrocardiogram (ECG) - QTc interval
In milliseconds (ms)
Time frame: Day 0-253
Laboratory safety parameters in blood - white blood cell count
In cells/mL
Time frame: Day 0-253
Laboratory safety parameters in blood - hemoglobin
In g/dL
Time frame: Day 0-253
Laboratory safety parameters in blood - platelets
In cells/cL
Time frame: Day 0-253
Laboratory safety parameters in blood - prothrombin time (PT)
In seconds
Time frame: Day 0-253
Laboratory safety parameters in blood - activated partial thromboplastin clotting time (aPTT)
In seconds
Time frame: Day 0-253
Laboratory safety parameters in blood - international normalised ratio (INR)
as a ration
Time frame: Day 0-253
Laboratory safety parameters in blood - blood urea nitrogen
In mg/dL
Time frame: Day 0-253
Laboratory safety parameters in blood - carbon dioxide
In mEq/L
Time frame: Day 0-253
Laboratory safety parameters in blood - creatinine
In mg/dL
Time frame: Day 0-253
Laboratory safety parameters in blood - glucose
In mg/dL
Time frame: Day 0-253
Laboratory safety parameters in blood - chloride
In mEq/L
Time frame: Day 0-253
Laboratory safety parameters in blood - potassium
In mEq/L
Time frame: Day 0-253
Laboratory safety parameters in blood - sodium
In mEq/L
Time frame: Day 0-253
white blood cell (WBC) count in cerebrospinal fluid (CSF)
1/µL
Time frame: Day 0-253
Protein levels in cerebrospinal fluid (CSF)
in g/L
Time frame: Day 0-253
Structural imaging assessment of any new abnormalities
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)
Time frame: Day 0-253
Percentage of participants with suicidal ideation or behaviour, as assessed by the Columbia suicide severity rating scale (C-SSRS).
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.
Time frame: Day 0-253
Concentrations of VO659 in cerebrospinal fluid (CSF)
in µg/mL
Time frame: _Day 1, 29, 57, 85, 120, 204, 253
Concentrations of VO659 in plasma
in µg/mL
Time frame: _Day 1, 29, 57, 85, 120, 204, 253
Maximum plasma concentration (Cmax) for VO659
in µg/mL
Time frame: Day 1, Day 85
Time to maximum plasma concentration (Tmax) for VO659
in days
Time frame: Day 1, Day 85]
Area under the plasma concentration time curve for VO659 from time 0 to last quantifiable concentration of (AUC0-t)
µg\*h/L
Time frame: Days 1, 2, 8, Days 85, 86, 92]
Terminal half-life (t1/2) of VO659 in plasma
In days
Time frame: Days 1, 2, 8
Terminal half-life (t1/2) of VO659 in cerebrospinal fluid (CSF)
in days
Time frame: Day 1 through Day 253
Not enrolling at this site.
Not enrolling at this site.
Plan to share: No
Started Feb 2023 (actual). Primary completion is estimated for Apr 2028, 61 months after the start.
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