Spinocerebellar Ataxia Type 1Phase 1/2NCT05822908
A Safety and Pharmacokinetics Trial of VO659 in SCA1, SCA3 and HD
A Phase 1/2 study testing VO659 in people with Spinocerebellar Ataxia Type 1 and Spinocerebellar Ataxia Type 3, run by Vico Therapeutics B. V. at 14 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 25 to 60 years
- Conditions the study is for
- Spinocerebellar Ataxia Type 1, Spinocerebellar Ataxia Type 3, Huntington Disease
- What is being tested?
- VO659
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 14 sitesin 6 countries
- Study dates
- 14 Feb 2023to 15 Oct 2028
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 60 years
- All sexes
- No healthy volunteers
- Adult
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:
- SCA1 and SCA3: mild to moderate disease with a Scale for Assessment and Rating of Ataxia (SARA) score of ≥3 and ≤18
- 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:
- SCA1: ≥41 contiguous, uninterrupted CAG repeats in the ATXN1 gene
- SCA3: ≥61 repeats in the ATXN3 gene
- 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
Trial locations and contacts
14 sites in 6 countries. Contact the study team or a site near you to ask about taking part.
14 sites in 6 countries
Germany4 sites, 4 recruiting
- Recruiting
Katholisches Klinikum Bochum
Bochum
Carsten Saft, Prof.
- Recruiting
Deutsches Zentrum fur Neurodegenerative Erkrankungen (DZNE)
Bonn
Jennifer Faber, Dr.
- Recruiting
Universitatsklinikum Essen - Neurologie
Essen
Tim Hagenacker, Prof.
- Recruiting
Universitatsklinikum Tübingen
Tübingen
Ludger Scholz, Prof Dr.
France3 sites, 3 recruiting
- Recruiting
Centre Hospitalier Universitaire dÁngers
Angers
Christophe Verny, Prof.
- Recruiting
CHU Gui de Chauliac Montpellier- Expert Center of Neurogenetic diseases, Department of Neurology
Montpellier
Cecilia Marelli, Dr.
- Recruiting
Universtiry Hospitals Pitie Salpetriere - Charles foix - Paris
Paris
Alexandra Durr, Prof. Dr.
Israel2 sites, 2 recruiting
- Recruiting
Meir Medical Center
Kfar Saba
Nirit Lev, Dr.
- Recruiting
Sourmansky Medical Center
Tel Aviv
Tanya Gurevich, Prof.
Netherlands2 sites
- Active, not recruiting
Leiden University Medical Center LUMC
Leiden
- Active, not recruiting
Radbout University Medical Centre
Nijmegen
United Kingdom2 sites, 2 recruiting
- Recruiting
University College London Hospitals NHS Foundation
London
Paola Giunti, Prof.
- Recruiting
John Radcliffe Hospital
Oxford
Richard Armstrong, Dr.
Denmark1 site, 1 recruiting
- Recruiting
Rigshospitalet
Copenhagen
Lena Hjermind, Dr.
About this study
Official title: A Phase 1/2a, Open-label Trial to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Doses of Intrathecally Administered VO659 in Participants With Spinocerebellar Ataxia Types 1, 3 and Huntington's Disease
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.
Read the detailed description
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).
- Being tested
- VO659
- Keywords
- hereditary ataxia, Machado-Joseph Disease (MJD)
- Medical subject headings
- Spinocerebellar Ataxias, Machado-Joseph Disease, Huntington Disease, Spinocerebellar Degenerations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VO659Drug
VO659 is an antisense oligonucleotide targeting CAG repeats in mRNA transcripts
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | 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. Receives: Drug: VO659 |
| Cohort 2 | Experimental | 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. Receives: Drug: VO659 |
| Cohort 3 | Experimental | 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. Receives: Drug: VO659 |
| Cohort 4 | Experimental | 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. Receives: Drug: VO659 |
| Cohort 5 | Experimental | 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. Receives: Drug: VO659 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: Day 0-253
Body weight
In kilograms
Measured: Day 0-253
Electrocardiogram (ECG) RR interval
In milliseconds (ms)
Measured: Day 0-253
Electrocardiogram (ECG) - PR interval
In milliseconds (ms)
Measured: Day 0-253
Electrocardiogram (ECG) - QTc interval
In milliseconds (ms)
Measured: Day 0-253
Laboratory safety parameters in blood - white blood cell count
In cells/mL
Measured: Day 0-253
Laboratory safety parameters in blood - hemoglobin
In g/dL
Measured: Day 0-253
Laboratory safety parameters in blood - platelets
In cells/cL
Measured: Day 0-253
Laboratory safety parameters in blood - prothrombin time (PT)
In seconds
Measured: Day 0-253
Laboratory safety parameters in blood - activated partial thromboplastin clotting time (aPTT)
In seconds
Measured: Day 0-253
Laboratory safety parameters in blood - international normalised ratio (INR)
as a ration
Measured: Day 0-253
Laboratory safety parameters in blood - blood urea nitrogen
In mg/dL
Measured: Day 0-253
Laboratory safety parameters in blood - carbon dioxide
In mEq/L
Measured: Day 0-253
Laboratory safety parameters in blood - creatinine
In mg/dL
Measured: Day 0-253
Laboratory safety parameters in blood - glucose
In mg/dL
Measured: Day 0-253
Laboratory safety parameters in blood - chloride
In mEq/L
Measured: Day 0-253
Laboratory safety parameters in blood - potassium
In mEq/L
Measured: Day 0-253
Laboratory safety parameters in blood - sodium
In mEq/L
Measured: Day 0-253
white blood cell (WBC) count in cerebrospinal fluid (CSF)
1/µL
Measured: Day 0-253
Protein levels in cerebrospinal fluid (CSF)
in g/L
Measured: 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)
Measured: 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.
Measured: Day 0-253
Secondary outcomes (7)
Concentrations of VO659 in cerebrospinal fluid (CSF)
in µg/mL
Measured: _Day 1, 29, 57, 85, 120, 204, 253
Concentrations of VO659 in plasma
in µg/mL
Measured: _Day 1, 29, 57, 85, 120, 204, 253
Maximum plasma concentration (Cmax) for VO659
in µg/mL
Measured: Day 1, Day 85
Time to maximum plasma concentration (Tmax) for VO659
in days
Measured: 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
Measured: Days 1, 2, 8, Days 85, 86, 92]
Terminal half-life (t1/2) of VO659 in plasma
In days
Measured: Days 1, 2, 8
Terminal half-life (t1/2) of VO659 in cerebrospinal fluid (CSF)
in days
Measured: Day 1 through Day 253
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2023
- Study start14 Feb 2023
- Primary completion1 Apr 2028 (estimated)
- Study completion15 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Spinocerebellar Ataxia Type 1Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Multiple ascending dose design
- Masking
- None (open label)
- Enrolment
- 68 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vico Therapeutics B. V.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Chief Medical Officer, Study director, VICO Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05822908
- Sponsor's protocol ID
- VO659-CT01
- Other IDs
- 2024-514328-18-00
- Status last verified
- Aug 2026
- First submitted
- 1 Mar 2023
- Last updated
- 19 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bonsor M, Ammar O, Schnoegl S, Wanker EE, Silva Ramos E. Polyglutamine disease proteins: Commonalities and differences in interaction profiles and pathological effects. Proteomics. 2024 Jun;24(12-13):e2300114. doi: 10.1002/pmic.202300114. Epub 2024 Apr 14.
PubMed 38615323Estevez-Fraga C, Tabrizi SJ, Wild EJ. Huntington's Disease Clinical Trials Corner: March 2024. J Huntingtons Dis. 2024;13(1):1-14. doi: 10.3233/JHD-240017.
PubMed 38489195