A Study to Evaluate the Safety, Biomarkers, and Efficacy of Tominersen in Individuals with Prodromal and Early Manifest Huntington’s Disease

Phase 1

• Conditions: Huntington's disease (HD); MedDRA version: 20.0Level: PTClassification code 10070668Term: Huntington's diseaseSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

• Registration Number: EUCTR2022-001991-32-PL
• Lead Sponsor: F.Hoffmann-La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-12-05
• Last Update Posted: 10 June 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

- Age 25-50 years
- Huntington’s disease (HD) gene expansion mutation carrier status
- Either:
- Prodromal HD or Early Manifest HD
- Estimated glomerular filtration rate >= 60 mL/min/1.73 m2 in at least one out of two maximum screening samples
- Total body weight > 40 kg and a body mass index within the range of 18-32 kg/m2
- Ability to read the words red, blue, and green and be fluent in the language of the Informed Consent and the tests used at the study site
- Ability to walk unassisted without a cane or walker and move about without a wheelchair on a daily basis as determined at screening and baseline visit (Day 1)
- Ability to undergo and tolerate MRI scans
- Ability to tolerate blood draws and lumbar punctures (LPs)
- Stable medical, psychiatric, and neurologic status as assessed by physician for at least 12 weeks prior to screening and at the time of enrollment
- Negative hepatitis B surface antigen test at screening
- Negative hepatitis C virus (HCV) antibody test at screening, or a positive HCV antibody test followed by a negative HCV ribonucleic acid (RNA) test at screening
- For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception and agree to refrain from donating eggs during the treatment period and for 5 months after the final dose of the study drug. Female participants must refrain from donating eggs during this same period
- For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom and agree to refrain from donating sperm during the treatment period and for 5 months after the final dose of the study drug to avoid exposing the embryo. Male participants must refrain from donating sperm during this same period

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 300
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

- History of attempted suicide or suicidal ideation with plan that required hospital visit and/or change in level of care within 12 months prior to screening
- Active psychosis, confusional state, or violent behavior, including aggression that could cause harm to self or others, over the 12 weeks prior to screening
- Clinical diagnosis of chronic migraines as per the International Headache Society Classification of Headache Disorders
- Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 5 months after the final dose of study drug
- Presence of an implanted shunt for the drainage of CSF or an implanted central nervous system (CNS) catheter
- Hydrocephalus
- History of deep brain stimulation
- Known human immunodeficiency viruses (HIV) infection
- An infection requiring oral or intravenous antibiotics within 14 days prior to screening, during screening and prior to randomization
- Anti-retroviral medications, including anti-retroviral medication taken as prophylaxis within 12 months of study enrollment
- Current or previous use of an antisense oligonucleotide (ASO) or any huntingtin protein (HTT) lowering therapy
- Treatment with investigational therapy within 4 weeks or 5 drug-elimination half-lives, whichever is longer, prior to screening
- Current or previous history of a primary independent psychotic disorder
- Current use of anti-psychotics for motor symptoms or mood stabilization and/or tetrabenazine, valbenazine, or deutetrabenazine at a dose that has not been stable for at least 12 weeks prior to screening or is anticipated to change during the study, including at screening
- Cholinesterase inhibitors, memantine, or riluzole use within 12 weeks from initiation of study treatment
- Current use of amantadine, anti-depressant or benzodiazepine at a dose that has not been stable for at least 12 weeks prior to screening or is anticipated to change during the study, including at screening
- Current use of supplements used to treat HD symptoms, including in an experimental setting, at a dose that has not been stable for at least 6 weeks prior to screening or is anticipated to change during the study, including at screening
- Anti-platelet or anticoagulant therapy within 14 days prior to screening
- History of bleeding diathesis or coagulopathy
- Platelet count less than the lower limit of normal
- History of gene therapy, cell transplantation, or brain surgery
- Planned brain surgery during the study
- Concurrent or planned participation in any interventional clinical study, including explicit pharmacological and non-pharmacological interventions. Observational studies are acceptable; however, data collection is not permitted between screening and baseline visits and throughout the duration of the study
- Poor peripheral venous access
- Scoliosis or spinal deformity or surgery making intrathecal (IT) injection not feasible in an outpatient setting and potentially interfering with distribution of tominersen up the neuraxis
- Malignancy within 5 years prior to screening, except basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated
- Preexisting intra-axial or extra-axial lesions as assessed by a centrally read MRI scan during the screening period

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified