VO659-CT01
Recruiting
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
This is a first-in-human clinical trial to look at the safety, tolerabilty, Pharmacokinetics and Pharmacodynamics of 4 doses of a new study drug called VO659, an ASO. This will be done in people with genetic disorders called spinocerebellar ataxia type 1(SCA), type 3(SCA3) or Huntington’s disease.
Another aim is to determine the concentrations of the study drug in the CSF and blood after single and multiple doses. Study drug will be given by lumbar(spine) injections.
Dose level 1 and 2 will only be done on SCA3. Then level 3-5 will include SCA1 and HD. Before each level the findings will be reviewed by a committee. This is known as a basket study which we have not seen before.
VO659 will target only the mutant allele.
This an open label.
Phase: 1 & 2
Subtype: Interventional Therapeutic
Primary Purpose: Treatment
Intervention Type: nucleic acid therapy
Primary Intervention: VO659
Mode of Action: mHTT Lowering, ASO
Duration: 45-58 weeks dependant on which group a participante is in.
Ages Eligible
for Study:
25 Years to 60 Years (Adult )
Sexes Eligible
for Study:
All
Accepts Healthy Volunteers:
No
- 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 HD with the following criteria:: 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. : ≥36 CAG repeats in the HTT gene.
- Please note there will be additional inclusion 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
- 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.
LOCATIONS
COUNTRIES
DENMARK
FRANCE
TRIAL SITE: Angers, France
Email: info@vicotx.com
TRIAL SITE: Montpellier, France
Email: info@vicotx.com
TRIAL SITE: Paris, France
Email: info@vicotx.com
GERMANY
TRIAL SITE: Bochum, Germany
Email: info@vicotx.com
TRIAL SITE: Bonn, Germany
Email: info@vicotx.com
TRIAL SITE: Essen, Germany
Email: info@vicotx.com
ISRAEL
TRIAL SITE: Kfar Saba, Israel
Email: info@vicotx.com
TRIAL SITE: Tel Aviv, Israel
Email: info@vicotx.com
NETHERLANDS
TRIAL SITE: Leiden, Netherlands
Email: info@vicotx.com
TRIAL SITE: Nijmegen, Netherlands
Email: info@vicotx.com
