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

NCT ID: NCT05822908

Last Updated: 2025-08-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-02-14
• Study Completion Date: 2028-10-15

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.

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).

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1

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.

Group Type: EXPERIMENTAL

VO659

Intervention Type: DRUG

VO659 is an antisense oligonucleotide targeting CAG repeats in mRNA transcripts

Cohort 2

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.

Group Type: EXPERIMENTAL

VO659

Intervention Type: DRUG

VO659 is an antisense oligonucleotide targeting CAG repeats in mRNA transcripts

Cohort 3

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.

Group Type: EXPERIMENTAL

VO659

Intervention Type: DRUG

VO659 is an antisense oligonucleotide targeting CAG repeats in mRNA transcripts

Cohort 4

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.

Group Type: EXPERIMENTAL

VO659

Intervention Type: DRUG

VO659 is an antisense oligonucleotide targeting CAG repeats in mRNA transcripts

Cohort 5

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.

Group Type: EXPERIMENTAL

VO659

Intervention Type: DRUG

VO659 is an antisense oligonucleotide targeting CAG repeats in mRNA transcripts

Interventions

VO659

VO659 is an antisense oligonucleotide targeting CAG repeats in mRNA transcripts

Intervention Type: DRUG

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Vico Therapeutics B. V.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chief Medical Officer

Role: STUDY_DIRECTOR

VICO Therapeutics

Locations

Rigshospitalet

Copenhagen, , Denmark

Site Status: RECRUITING

Centre Hospitalier Universitaire dÁngers

Angers, , France

Site Status: RECRUITING

CHU Gui de Chauliac Montpellier- Expert Center of Neurogenetic diseases, Department of Neurology

Montpellier, , France

Site Status: RECRUITING

Universtiry Hospitals Pitie Salpetriere - Charles foix - Paris

Paris, , France

Site Status: RECRUITING

Katholisches Klinikum Bochum

Bochum, , Germany

Site Status: RECRUITING

Deutsches Zentrum fur Neurodegenerative Erkrankungen (DZNE)

Bonn, , Germany

Site Status: RECRUITING

Universitatsklinikum Essen - Neurologie

Essen, , Germany

Site Status: RECRUITING

Universitatsklinikum Tübingen

Tübingen, , Germany

Site Status: RECRUITING

Meir Medical Center

Kfar Saba, , Israel

Site Status: RECRUITING

Sourmansky Medical Center

Tel Aviv, , Israel

Site Status: RECRUITING

Leiden University Medical Center LUMC

Leiden, , Netherlands

Site Status: RECRUITING

Radbout University Medical Centre

Nijmegen, , Netherlands

Site Status: RECRUITING

University College London Hospitals NHS Foundation

London, , United Kingdom

Site Status: RECRUITING

John Radcliffe Hospital

Oxford, , United Kingdom

Site Status: RECRUITING

Countries

Denmark; France; Germany; Israel; Netherlands; United Kingdom

Central Contacts

Chief Medical Officer

Role: CONTACT

info@vicotx.com

+31 71 2036800

Facility Contacts

Lena Hjermind, Dr.

Role: primary

Christophe Verny, Prof.

Role: primary

Cecilia Marelli, Dr.

Role: primary

Alexandra Durr, Prof. Dr.

Role: primary

Carsten Saft, Prof.

Role: primary

Jennifer Faber, Dr.

Role: primary

Tim Hagenacker, Prof.

Role: primary

Ludger Scholz, Prof Dr.

Role: primary

Nirit Lev, Dr.

Role: primary

Tanya Gurevich, Prof.

Role: primary

Susanne de Bot, Dr.

Role: primary

Bart van de Warrenburg, Prof.

Role: primary

Paola Giunti, Prof.

Role: primary

Richard Armstrong, Dr.

Role: primary

References

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.

Reference Type: DERIVED

PMID: 38489195 (View on PubMed)

Other Identifiers

2024-514328-18-00

Identifier Type: CTIS

Identifier Source: secondary_id

VO659-CT01

Identifier Type: -

Identifier Source: org_study_id