Authorised Phase I and Phase II (Integrated)- First administration to humans Spinocerebellar ataxia types 1, 3 and Huntington's disease

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

EU CTIS ID: 2024-514328-18-00

What this study is testing

To evaluate the safety and tolerability of multiple doses and regimens of intrathecal (IT) lumbar bolus administrations of VO659 in participants with clinically manifest spinocerebellar ataxia (SCA)1, SCA3, or Huntington’s disease (HD)

Phase I and Phase II (Integrated)- First administration to humans

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

Informed Consent 1. Provide written informed consent (signed and dated). Participants should be assessed for their ability to give informed consent using the Evaluation to Sign Consent tool.
Age 2. Is ≥25 and ≤60 years of age, of any gender, at the time of signing the informed consent.
Type of Indications and Disease Characteristics 3. Have SCA1, SCA3 or HD meeting 1 of the following criteria: a. SCA1 and SCA3: mild to moderate disease with a Scale for Assessment and Rating of Ataxia (SARA) score of ≥3 and ≤18 b. 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 details, see Section 8.6.1). For each indication the requirements are: a. SCA1: ≥41 contiguous, uninterrupted CAG repeats in Ataxin 1 gene / mRNA transcript (ATXN1) b. SCA3: ≥61 repeats in Ataxin 3 gene / mRNA transcript (ATXN3) c. HD: ≥40 CAG repeats in Huntingtin gene/mRNA transcript (HTT). NOTE: Genetic testing will be performed during screening, which will serve as a reference for criterion.
Have good general health, in the opinion of the investigator, apart from having SCA1, SCA3, or HD. NOTE: Patients with a chronic illness (e.g., hypertension) will be eligible if in the opinion of the investigator, the illness is stable and well-controlled and will not impact the primary objectives of the trial.
Weight 6. Body weight of ≥50 kg and body mass index within the range of ≥17.5 and <32.5 kg/m2 (inclusive).

You likely can't join if

Medical Conditions 1. Have any condition that would prevent participation in trial assessments.
Have any known history of hypersensitivity or allergies to the antisense oligonucleotide (VO659) or any excipient contained in the IMP.
Have any significant (moderate or severe) acute or chronic liver or kidney disease.
Have deviations of any of the following laboratory parameters at screening:  Aspartate aminotransferase >2.0 x Upper Limit of normal range (ULN)  Alanine aminotransferase >2.0 x ULN  Total bilirubin > 1.5 x ULN  Platelets <100,000/µl (i.e., <100 x 109 /L)  Estimated glomerular filtration rate <45 mL/min/1.73m2 based on the modification of diet in renal disease formula (see Section 10.5)
Have uncompensated cardiovascular disorder, any past or present cardiac arrhythmia, QTcF values on screening ECG of > 450 ms for males and > 470 ms for females, familial history of long QT syndrome or sudden unexpected death.
Have a history of uncontrolled hypokalaemia or hypomagnesaemia.

See the full eligibility criteria

Who can join

Informed Consent 1. Provide written informed consent (signed and dated). Participants should be assessed for their ability to give informed consent using the Evaluation to Sign Consent tool.
Age 2. Is ≥25 and ≤60 years of age, of any gender, at the time of signing the informed consent.
Type of Indications and Disease Characteristics 3. Have SCA1, SCA3 or HD meeting 1 of the following criteria: a. SCA1 and SCA3: mild to moderate disease with a Scale for Assessment and Rating of Ataxia (SARA) score of ≥3 and ≤18 b. 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 details, see Section 8.6.1). For each indication the requirements are: a. SCA1: ≥41 contiguous, uninterrupted CAG repeats in Ataxin 1 gene / mRNA transcript (ATXN1) b. SCA3: ≥61 repeats in Ataxin 3 gene / mRNA transcript (ATXN3) c. HD: ≥40 CAG repeats in Huntingtin gene/mRNA transcript (HTT). NOTE: Genetic testing will be performed during screening, which will serve as a reference for criterion.
Have good general health, in the opinion of the investigator, apart from having SCA1, SCA3, or HD. NOTE: Patients with a chronic illness (e.g., hypertension) will be eligible if in the opinion of the investigator, the illness is stable and well-controlled and will not impact the primary objectives of the trial.
Weight 6. Body weight of ≥50 kg and body mass index within the range of ≥17.5 and <32.5 kg/m2 (inclusive).
Reproductive status and Contraceptive/Barrier Requirements 7. Is willing to follow contraceptive requirements per local regulations regarding the methods of contraception for those participating in clinical trials. In case local regulations deviate from the contraception methods listed in Section 10.4, local regulations apply and will be described in the Informed Consent Form. a. Male participants: Applicable for Europe (NOTE: details according to the Clinical Trial Facilitation Group [CTFG] Contraception Guidance Version 1.1, issued 2020; see Section 10.4): Non-sterilised males who are sexually active with a female partner of childbearing potential: Agreement to use a condom as a method of contraception during the entire period from first IMP (VO659) administration up to 90 days after the last IMP administration and not to donate sperm during this period. Additionally, contraception for the female partner of childbearing potential should be considered. b. Female participants: Applicable for Europe (NOTE: Details according to CTFG Contraception Guidance version 1.1, issued 2020; see Section 10.4): Women of childbearing potential: a negative result in a pregnancy test at screening and prior to each IMP administration AND agreement to practice a highly effective method of contraception during the entire period from informed consent up to 6 months after the last IMP administration. A woman is considered of childbearing potential, i.e., fertile, following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A postmenopausal state is defined as no menses for at least 12 months without an alternative medical cause. Women under the age of 55 years must have both no menses for at least 12 months and a follicle-stimulating hormone (FSH) level >40m IU/mL (while not on any therapy that may interfere with FSH levels) in order to confirm menopause. In the absence of 12 months of amenorrhea, an FSH measurement in itself is insufficient to establish menopause.

What rules you out

Medical Conditions 1. Have any condition that would prevent participation in trial assessments.
Have any known history of hypersensitivity or allergies to the antisense oligonucleotide (VO659) or any excipient contained in the IMP.
Have any significant (moderate or severe) acute or chronic liver or kidney disease.
Have deviations of any of the following laboratory parameters at screening:  Aspartate aminotransferase >2.0 x Upper Limit of normal range (ULN)  Alanine aminotransferase >2.0 x ULN  Total bilirubin > 1.5 x ULN  Platelets <100,000/µl (i.e., <100 x 109 /L)  Estimated glomerular filtration rate <45 mL/min/1.73m2 based on the modification of diet in renal disease formula (see Section 10.5)
Have uncompensated cardiovascular disorder, any past or present cardiac arrhythmia, QTcF values on screening ECG of > 450 ms for males and > 470 ms for females, familial history of long QT syndrome or sudden unexpected death.
Have a history of uncontrolled hypokalaemia or hypomagnesaemia.
Have a history of hospitalisation for any major medical or surgical procedure involving general anaesthesia within 6 weeks of screening or planned during the trial.
Have long-term neurological consequences of COVID-19 / SARS-CoV-2 infection that have not resolved or stabilised at the time of screening.
Have a history of attempted suicide, or suicidal ideation with a plan that required hospital admission and/or change in level of care within 12 months prior to screening. For patients with (i) a suicide ideation score ≥4 on the Columbia Suicide Severity Rating Scale (C-SSRS) within the last 12 months, or (ii) suicidal behaviours within the last 12 months (as measured by the answer “Yes” on any of the C-SSRS Suicidal Behaviour Items), a risk assessment should be done by an appropriately-qualified mental health professional (e.g., a psychiatrist or licensed clinical psychologist) to assess whether it is safe for the patient to participate in the trial.
Have a history of psychosis, bipolar disorder or schizophrenia and patients deemed to be at significant risk of an acute depressive episode, confusional state or violent behaviour.
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.
Have an acute infection or febrile illness at the time of each dosing, or ongoing systemic antiviral or antimicrobial therapy that will not be completed at least 3 days prior to dosing.
Prior/Concomitant Therapy 20. Presence of an implanted shunt for the drainage of CSF or an implanted central nervous system (CNS) catheter
Treatment with another IMP, biological agent, or device within 3 months prior to screening, or 5 half-lives of the investigational agent, whichever is longer
Riluzole use unless stable dose for at least 4 weeks prior to screening and with a dose regimen that is not anticipated to change during the trial.
Treatment for spasticity unless stable dose for at least 4 weeks prior to screening and with a dose regimen that is not anticipated to change during the trial
Antidepressant or benzodiazepine use unless stable dose for at least 12 weeks prior to screening and with a dose regimen that is not anticipated to change during the trial
Current or recent (within the last 3 months) use of antipsychotics (prescribed for psychosis) acetylcholinesterase inhibitors, memantine or amantadine. Use of antipsychotics (prescribed for treatment of motor symptoms) and/or tetrabenazine/deutetrabenazine and valproic acid are not permitted unless stable for at least 12 weeks prior to screening and with a dose regimen that is not anticipated to change during the trial.
Drugs known to prolong the QT interval (see Section 10.7), unless the treatment stopped at least five times the respective drug’s 1/2 in advance of the first dosing with VO659.
Supplement use (e.g., coenzyme Q10, vitamins, creatine), unless stable dose for 6 weeks prior to screening and with a dose regimen that is not anticipated to change during the trial.
Antiplatelet or anticoagulant therapy within 14 days prior to screening or anticipated use during the trial, including but not limited to dipyridamole, warfarin, dabigatran, rivaroxaban, apixaban, and edoxaban; aspirin ≤100 mg/day or clopidogrel are permitted
Prior treatment with an antisense oligonucleotide (including small interfering RNA (siRNA)).
Have 1 or more pathogenic mutation(s) in another polyglutamine (polyQ) disease gene, i.e., ATXN2, calcium voltage-gated channel subunit Alpha1 A gene / mRNA transcript (CACNA1A), Ataxin 7 gene / mRNA transcript (ATXN7), TATA-box binding protein gene / mRNA transcript (TBP), androgen receptor gene/mRNA transcript (AR), Ataxin 1 gene/mRNA transcript (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. Pathogenic mutations are defined as: ≥41 contiguous, uninterrupted CAG repeats in ATXN1; ≥61 repeats in ATXN3; ≥36 CAG repeats in HTT; ≥38 CAG repeats in AR; ≥48 CAG repeats in ATN1; ≥33 CAG repeats in ATXN2; ≥34 CAG repeats in ATXN 7; ≥20 CAG repeats in CACNA1A; ≥41 CAG repeats in TBP.
History of gene therapy or cell transplantation or any experimental brain surgery.
Adenoviral vector-based vaccination within 45 days of the first dosing.
History of chemical meningitis
Prior/Concurrent Clinical Trial Experience 33. Concurrent or planned concurrent participation in any other clinical trial evaluating IMPs; for observational and non-interventional trials, the same applies, unless approved by the Sponsor’s Medical Expert or Medical Monitor.
Other Exclusions. Pregnant or breast-feeding (lactating) women or women who plan to become pregnant or breast-feed during the trial.
Have a history of any drug or alcohol abuse in the past 5 years or regular daily alcohol consumption, in any form, of more than 24 g (for men) or 12 g (for women). NOTE: 24 g of alcohol corresponds to approximately 500 mL of usual beer or 250 mL of usual wine; 12 g of alcohol corresponds to approximately 250 mL of usual beer or 125 mL of usual wine.
Have a positive urine drug screen for amphetamines, barbiturates, cocaine, opiates, cannabinoids, or benzodiazepines at the screening visit. NOTE: benzodiazepines are acceptable if consistent with the declared concomitant medication which may include benzodiazepine use with a stable dose for at least 12 weeks prior to screening – see exclusion criterion No.24. NOTE: cannabinoids/tetrahydrocannabinol (THC) are acceptable if use is stable for at least 12 weeks prior to screening and for a medical but not recreational purposes.
Is unable to undergo and tolerate MRI scans, e.g., due to metal implants including MRIincompatible intrauterine devices, claustrophobia, any movement disorder of a severity that precludes MRI scans or jeopardises the quality of the MRI scan, or any other condition that renders MRI scans intolerable for the patient.
Have a close affiliation with the Sponsor or the trial site, e.g., a close relative of the investigator, dependent person (e.g., employee or student of the trial site).
Have clinical diagnosis of moderate or severe chronic migraines or history of the postlumbar-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 a history of bleeding diathesis or coagulopathy, or a 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 a history of any malignancy or obligatory precancerous condition of any organ system, except cervical carcinoma of Stage 1B or less, or non-invasive basal cell or squamous cell skin carcinoma that has been successfully treated.
Have inherited or acquired immunodeficiency, including human immunodeficiency virus infection
Have positive serology for hepatitis B surface antigen or active hepatitis C infection.

The study team makes the final eligibility decision.

Where it's taking place

Israel
United Kingdom

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 18-64 years. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include Israel; United Kingdom. Enter your location above to see the nearest site and check your eligibility.

Explore other conditions

Obesity Type 2 diabetes Type 1 diabetes Prediabetes Weight loss Metabolic syndrome High cholesterol High triglycerides High blood pressure PCOS Hypothyroidism Thyroid disease Gout Fatty liver disease (NAFLD/NASH)Heart failure Coronary artery disease

BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.