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

NCT05822908 | Recruiting Phase 1 DMC

• 2 other identifiers: VO659-CT012024-514328-18-00
• Study Type: interventional
• Target: 68
• Locations: 6 countries
• Sites: 14

Brief 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.

Conditions

Spinocerebellar Ataxia Type 1; Spinocerebellar Ataxia Type 3; Huntington Disease

Keywords

hereditary ataxia; Machado-Joseph Disease (MJD)

Outcome Measures

Primary Outcomes (23)

• 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

  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

  Day 0-253

• Body weight

  In kilograms

  Day 0-253

• Electrocardiogram (ECG) RR interval

  In milliseconds (ms)

  Day 0-253

• Electrocardiogram (ECG) - PR interval

  In milliseconds (ms)

  Day 0-253

• Electrocardiogram (ECG) - QTc interval

  In milliseconds (ms)

  Day 0-253

• Laboratory safety parameters in blood - white blood cell count

  In cells/mL

  Day 0-253

• Laboratory safety parameters in blood - hemoglobin

  In g/dL

  Day 0-253

• Laboratory safety parameters in blood - platelets

  In cells/cL

  Day 0-253

• Laboratory safety parameters in blood - prothrombin time (PT)

  In seconds

  Day 0-253

• Laboratory safety parameters in blood - activated partial thromboplastin clotting time (aPTT)

  In seconds

  Day 0-253

• Laboratory safety parameters in blood - international normalised ratio (INR)

  as a ration

  Day 0-253

• Laboratory safety parameters in blood - blood urea nitrogen

  In mg/dL

  Day 0-253

• Laboratory safety parameters in blood - carbon dioxide

  In mEq/L

  Day 0-253

• Laboratory safety parameters in blood - creatinine

  In mg/dL

  Day 0-253

• Laboratory safety parameters in blood - glucose

  In mg/dL

  Day 0-253

• Laboratory safety parameters in blood - chloride

  In mEq/L

  Day 0-253

• Laboratory safety parameters in blood - potassium

  In mEq/L

  Day 0-253

• Laboratory safety parameters in blood - sodium

  In mEq/L

  Day 0-253

• white blood cell (WBC) count in cerebrospinal fluid (CSF)

  1/µL

  Day 0-253

• Protein levels in cerebrospinal fluid (CSF)

  in g/L

  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)

  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.

  Day 0-253

Secondary Outcomes (7)

• Concentrations of VO659 in cerebrospinal fluid (CSF)

  _Day 1, 29, 57, 85, 120, 204, 253

• Concentrations of VO659 in plasma

  _Day 1, 29, 57, 85, 120, 204, 253

• Maximum plasma concentration (Cmax) for VO659

  Day 1, Day 85

• Time to maximum plasma concentration (Tmax) for VO659

  Day 1, Day 85]

• Area under the plasma concentration time curve for VO659 from time 0 to last quantifiable concentration of (AUC0-t)

  Days 1, 2, 8, Days 85, 86, 92]

Study Arms (5)

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.

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.

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.

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.

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.

Drug: VO659

Interventions

VO659 DRUG

VO659 is an antisense oligonucleotide targeting CAG repeats in mRNA transcripts

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5

Eligibility Criteria

• Age: 25 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Vico Therapeutics B. V.: lead

Study Sites (14)

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

RECRUITING

Radbout University Medical Centre

Nijmegen, Netherlands

RECRUITING

University College London Hospitals NHS Foundation

London, United Kingdom

RECRUITING

John Radcliffe Hospital

Oxford, United Kingdom

RECRUITING

Related Publications (1)

• Estevez-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.

  PMID: 38489195 DERIVED

MeSH Terms

Conditions

Spinocerebellar Ataxias; Machado-Joseph Disease; Huntington Disease; Spinocerebellar Degenerations

Condition Hierarchy (Ancestors)

Cerebellar Ataxia; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Ataxia; Dyskinesias; Neurologic Manifestations; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Basal Ganglia Diseases; Dementia; Chorea; Movement Disorders; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Chief Medical Officer

  VICO Therapeutics

  STUDY DIRECTOR

Central Study Contacts

Chief Medical Officer

CONTACT

+31 71 2036800; info@vicotx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Multiple ascending dose design

Study Record Dates

• First Submitted: March 1, 2023
• First Posted: April 21, 2023
• Study Start: February 14, 2023
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): October 15, 2028
• Last Updated: August 28, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1); IL (2); DE (4); FR (3); NL (2); GB (2)