Huntington Disease
Conditions
Keywords
Prodromal and Early Manifest Huntington's Disease
Brief summary
This study will evaluate the safety, biomarkers, and efficacy of tominersen compared with placebo in participants with prodromal and early manifest Huntington's Disease (HD).
Interventions
DRUGTominersen
Tominersen will be administered at the dose and schedule specified in the protocol.
DRUGPlacebo
Matching placebo administered IT, Q16W during the DB period.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
25 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
DB Period: * HD gene expansion mutation carrier status with a cytosine-adenine-guanine-age product (CAP) score of 400-500 inclusive * Either: * Prodromal HD (defined as Diagnostic Confidence Level (DCL) 2 to 3, Independence Scale (IS) ≥70, and TFC ≥8); Or * Early manifest HD (defined as DCL 4, IS ≥70, and TFC ≥8) * Total body weight \> 40 kilograms (kg) and a body mass index (BMI) within the range of 18-32 kilograms per meter square (kg/m\^2) * Study companion OLE Period: * Participants must have completed the DB treatment period * Participants must remain in the DB Safety follow-up period until OLE period starts
Exclusion criteria
DB Period: * Current or previous use of an antisense oligonucleotide (ASO) (including small interfering ribonucleic acid \[RNA\]) or any HTT lowering therapy (including tominersen) * Anti-platelet or anticoagulant therapy within 14 days prior to screening or anticipated use during the study, including, but not limited to, aspirin (unless ≤ 81 milligrams per day \[mg/day\]), clopidogrel, dipyridamole, warfarin, dabigatran, rivaroxaban, apixaban, and heparin * History of gene therapy, cell transplantation, or brain surgery * Hydrocephalus * Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 5 months after the final dose of study drug * History of attempted suicide or suicidal ideation with plan (i.e., active suicidal ideation) that required hospital visit and/or change in level of care within 12 months prior to screening OLE Period: * Early discontinuation from the DB treatment and the safety follow-up (SFU) periods * Pregnant or breastfeeding, or with the intention of becoming pregnant during the study or within the timeframe in which contraception is required * Current or previous use of an ASO other than tominersen (including small interfering RNA) or any other HTT-lowering therapy * Hydrocephalus * Received any active investigational treatment other than tominersen during or since completion of the DB treatment period Key inclusions/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DB Period: Incidence and Severity of Adverse Events (AEs), With Severity Determined According to the AE Severity Grading Scale | Up to approximately 36 months | — |
| DB Period: Change From Baseline in Clinical Laboratory Results - Cerebrospinal Fluid (CSF) White Blood Cell (WBC) | Baseline visit (Day 1), and Months 4, 8, 9, 12, 16 | — |
| DB Period: Change From Baseline in Clinical Laboratory Results - CSF Protein | Baseline visit (Day 1), and Months 4, 8, 9, 12, 16 | — |
| DB Period: Change From Baseline in Structural Magnetic Resonance Imaging (MRI) Assessing Any New Abnormalities Including Radiographic Features Consistent With Hydrocephalus and Other Relevant MRI Safety Findings | Baseline, Months 4, 8, 12, 16 and up to approximately 36 months | — |
| DB Period: Percentage Change From Baseline in Geometric Means of CSF Mutant Huntingtin (mHTT) Protein Levels at Month 9 | Baseline, Month 9 | — |
| DB Period: Change From Baseline in Composite Unified Huntington's Disease Rating Scale (cUHDRS) Scores (non-U.S. Sites) at 16 Months | Baseline to 16 months | Change in scores on the scale. |
| DB Period: Change From Baseline in Total Functional Capacity (TFC) Scores (U.S. Sites) at 16 Months | Baseline to 16 months | Change in scores on the scale. |
| OLE Period: Incidence and Severity of AEs, With Severity Determined According to the AE Severity Grading Scale | Up to approximately 29 months | — |
| OLE Period: Change Over Time in Clinical Laboratory Results - CSF WBC | Up to approximately 24 months | — |
| OLE Period: Change Over Time in Clinical Laboratory Results - CSF Protein | Up to approximately 24 months | — |
| OLE Period: Change From Baseline in Structural MRI Assessing Any New Abnormalities, Including Radiographic Features Consistent With Hydrocephalus and Other Relevant MRI Safety Findings | Up to approximately 29 months | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| DB Period: Change From Baseline in Montreal Cognitive Assessment (MoCA) Scores | Baseline, Months 4, 8, 12, 16 and up to approximately 36 months | — |
| DB Period: Percentage of Participants With Suicidal Ideation or Behavior (I/B), as Assessed by C-SSRS Score at Each Visit, Including Detailed Focus on Any Individual Cases Identified as Having Severe I/B During the Study Conduct | Up to approximately 36 months | C-SSRS=Columbia-suicide Severity Rating Scale |
| DB Period: Change From Baseline at 16 Months in TFC (non-U.S. Sites) Scores | Baseline to 16 months | — |
| DB Period: Change From Baseline at 16 Months in cUHDRS (U.S. Sites) Scores | Baseline to 16 months | — |
| DB Period: Change From Baseline at 16 Months in Symbol Digit Modalities Test (SDMT) Scores | Baseline to 16 months | — |
| DB Period: Change From Baseline at 16 Months in Stroop Word Reading (SWR) Score | Baseline to 16 months | — |
| DB Period: Change From Baseline at 16 Months in Total Motor Score (TMS) | Baseline to 16 months | — |
| DB Period: Change From Baseline in CSF Neurofilament Light Chain (NfL) Levels at 16 Months | Baseline to 16 months | — |
| DB Period: Incidence of Anti-drug Antibodies (ADAs) at Specified Timepoints Relative to the Prevalence of ADAs at Baseline | Baseline up to approximately 36 months | — |
| DB Period: Titers Determined if ADAs are Identified | Baseline up to approximately 36 months | — |
| OLE Period: Change Over Time in TFC Score | Up to approximately 29 months | — |
| OLE Period: Change Over Time in cUHDRS Score | Up to approximately 29 months | — |
| OLE Period: Change Over Time in SDMT Score | Up to approximately 29 months | — |
| OLE Period: Change Over Time in TMS | Up to approximately 29 months | — |
| OLE Period: Change Over Time in SWR Score | Up to approximately 29 months | — |
| OLE Period: Change Over Time in MoCA Score | Up to approximately 29 months | — |
| OLE Period: Percentage of Participants With Suicidal I/B, as Assessed by C-SSRS Score at Each Visit, Including Detailed Focus on Any Individual Cases Identified as Having Severe I/B During the Study Conduct | Up to approximately 29 months | — |
| OLE Period: Incidence of ADAs at Specified Timepoints | Up to approximately 29 months | — |
Countries
Argentina, Australia, Austria, Canada, Denmark, France, Germany, Italy, New Zealand, Poland, Portugal, Spain, Switzerland, United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Outcome results
None listed