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This study will test the safety, tolerability, pharmacokinetics and pharmacodynamics of RO7234292 administered intrathecally to adult patients with Huntington's Disease.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| RO7234292 Monthly | Experimental | RO7234292 is administered every 28 days intrathecally for 14 months. |
|
| RO7234292 Bimonthly | Experimental | RO7234292 is administered every 56 days intrathecally for 14 months following 2 monthly doses to serve as a loading dose. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| RO7234292 (RG6042) | Drug | Intrathecal injection |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Adverse Events | Adverse Events include Adverse Events that started at or after Date/Time of First Exposure to Treatment and procedure-related Adverse Events occurring before the start of treatment. | From baseline up to 18 months |
| Measure | Description | Time Frame |
|---|---|---|
| RO7234292 CSF Trough Concentrations by Study Day Prior to Monthly and Bimonthly IT Administration of 120 mg RO7234292 (Primary Analysis) | From baseline to Day 421 | |
| CSF mHTT Protein Concentration Logarithmic Value Change in Geometric Mean (95%CI) From Baseline |
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Key Inclusion Criteria:
Key Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The University of British Columbia; The Centre for Huntington Disease | Vancouver | British Columbia | V6T 2B5 | Canada | ||
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Participant eligibility for the study was determined within 4 weeks prior to participant entry into the Treatment Period.
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| ID | Title | Description |
|---|---|---|
| FG000 | RO7234292 Monthly | RO7234292 was administered intrathecally every 28 days for 14 months. |
| FG001 | RO7234292 Bimonthly | RO7234292 was administered intrathecally every 56 days for 14 months following 2 monthly doses to serve as a loading dose. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 30, 2018 |
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The results of the planned analysis related to mHTT protein levels in CSF are reported
| From Baseline to Day 421 |
| Mean Percentage Change in Ventricular Volume Boundary Shift Integral From Baseline to 15 Months | Baseline up to 15 months |
| Mean Percentage Change in Caudate Volume Boundary Shift Integral From Baseline to 15 Months | Baseline up to 15 months |
| Mean Percentage Change in Whole Brain Volume Boundary Shift Integral From Baseline to 15 Months | Baseline up to 15 months |
| EEG Parameters: Mean Change From Baseline to 15 Months in Absolute Power [8-12Hz] | Baseline to 15 Months |
| Mean Change From Baseline in Huntington's Disease Cognitive Assessment Battery Composite Score | HD Cognitive Assessment Battery (HD-CAB) was developed to assess cognitive dysfunction in late premanifest and early manifest HD patients. HD-CAB combines scores from six cognitive tests: SDMT, Self-Paced Tapping, Emotional Recognition, CANTAB One Touch Stocking, Hopkins Verbal Learning Test - Revised, and Trail-Making Test. A multi-component score is derived by transforming the subject's score on each cognitive test to a z-score. Using z-scores permits the combination of test scores with different scales. Unlike other measures that use an external reference population to create z-scores, HD-CAB uses the baseline data of the study. Individually, for each of the six cognitive tests, the study baseline mean is subtracted from the subject's score, and this value is divided by the study baseline standard deviation. The six z-scores are averaged to produce the HD-CAB score. A positive change from baseline indicates improvement in cognitive function; a negative change indicates worsening. | Baseline to 15 Months |
| Charité - Universitätsmedizin Berlin, Campus Charité Mitte; Klinik für Psychiatrie und Psychotherapi |
| Berlin |
| 10117 |
| Germany |
| St. Josef and St. Elisabeth GmbH ; Klinikum Bochum, Zentralapotheke | Bochum | 44791 | Germany |
| Universitaetsklinikum Ulm | Ulm | 89081 | Germany |
| NIHR Welcome Trust Birmingham CRF - University Hospitals Birmingham; Department of Neuropsychiatry | Birmingham | B15 2FG | United Kingdom |
| University of Cambridge - John van Geest Centre for Brain Repair | Cambridge | CB2 0PY | United Kingdom |
| Cardiff University School of Medicine; Institute of Psychological Medicine Clinical Neurosciences | Cardiff | CF24 4HQ | United Kingdom |
| Leonard Wolfson Experimental Neurology Centre | London | WC1N 3BG | United Kingdom |
| Central Manchester University Hospitals NHS Foundation Trust; Manchester Centre for Genomic Medicine | Manchester | M13 9WL | United Kingdom |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | RO7234292 Monthly | RO7234292 was administered intrathecally every 28 days for 14 months. |
| BG001 | RO7234292 Bimonthly | RO7234292 was administered intrathecally every 56 days for 14 months following 2 monthly doses to serve as a loading dose. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Race/Ethnicity, Customized | One participant's race is known, was reported but cannot be classified in Roche database | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants With Adverse Events | Adverse Events include Adverse Events that started at or after Date/Time of First Exposure to Treatment and procedure-related Adverse Events occurring before the start of treatment. | Safety population comprising all participants that were randomized and received at least one dose of RO7234292. | Posted | Number | Percentage of participants | From baseline up to 18 months |
|
|
| |||||||||||||||||||||||||||||
| Secondary | RO7234292 CSF Trough Concentrations by Study Day Prior to Monthly and Bimonthly IT Administration of 120 mg RO7234292 (Primary Analysis) | CSF Trough Concentrations were reported following study drug administration. Data for Bi-monthly arm was not collected on days 57, 113, 169, 225, 281, 337, 393. Here "Number Analyzed" represents number of participants from whom samples were collected and analyzed. | Posted | Geometric Mean | Full Range | ng/mL | From baseline to Day 421 |
|
| ||||||||||||||||||||||||||||||
| Secondary | CSF mHTT Protein Concentration Logarithmic Value Change in Geometric Mean (95%CI) From Baseline | The results of the planned analysis related to mHTT protein levels in CSF are reported | ITT Population. The data for Bi-monthly arm was not collected on days 113, 169, 225, 281, 337, 393. Here "Number Analyzed" represents number of participants from whom samples were collected and analyzed | Posted | Geometric Mean | 95% Confidence Interval | Log (10) fmol/L | From Baseline to Day 421 |
|
| |||||||||||||||||||||||||||||
| Secondary | Mean Percentage Change in Ventricular Volume Boundary Shift Integral From Baseline to 15 Months | Here "Number of Participants Analyzed" represents number of participants from whom data were collected and analyzed. Only data that passed the QC imaging process were included in the analysis. | Posted | Mean | Standard Deviation | Percentage change | Baseline up to 15 months |
|
| ||||||||||||||||||||||||||||||
| Secondary | Mean Percentage Change in Caudate Volume Boundary Shift Integral From Baseline to 15 Months | Here "Number of Participants Analyzed" represents number of participants from whom data were collected and analyzed. | Posted | Mean | Standard Deviation | Percentage change | Baseline up to 15 months |
|
| ||||||||||||||||||||||||||||||
| Secondary | Mean Percentage Change in Whole Brain Volume Boundary Shift Integral From Baseline to 15 Months | Here "Number of Participants Analyzed" represents number of participants from whom data were collected and analyzed. | Posted | Mean | Standard Deviation | Percentage change | Baseline up to 15 months |
|
| ||||||||||||||||||||||||||||||
| Secondary | EEG Parameters: Mean Change From Baseline to 15 Months in Absolute Power [8-12Hz] | Posted | Mean | Standard Deviation | log10(mircrovolts^2) | Baseline to 15 Months |
|
| |||||||||||||||||||||||||||||||
| Secondary | Mean Change From Baseline in Huntington's Disease Cognitive Assessment Battery Composite Score | HD Cognitive Assessment Battery (HD-CAB) was developed to assess cognitive dysfunction in late premanifest and early manifest HD patients. HD-CAB combines scores from six cognitive tests: SDMT, Self-Paced Tapping, Emotional Recognition, CANTAB One Touch Stocking, Hopkins Verbal Learning Test - Revised, and Trail-Making Test. A multi-component score is derived by transforming the subject's score on each cognitive test to a z-score. Using z-scores permits the combination of test scores with different scales. Unlike other measures that use an external reference population to create z-scores, HD-CAB uses the baseline data of the study. Individually, for each of the six cognitive tests, the study baseline mean is subtracted from the subject's score, and this value is divided by the study baseline standard deviation. The six z-scores are averaged to produce the HD-CAB score. A positive change from baseline indicates improvement in cognitive function; a negative change indicates worsening. | Posted | Mean | Standard Deviation | z-score | Baseline to 15 Months |
|
From baseline to up to 18 months
Safety population comprising all participants that were randomized and received at least one dose of RO7234292
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | RO7234292 Monthly | RO7234292 was administered intrathecally every 28 days for 14 months. | 1 | 23 | 4 | 23 | 22 | 23 |
| EG001 | RO7234292 Bimonthly | RO7234292 was administered intrathecally every 56 days for 14 months following 2 monthly doses to serve as a loading dose. | 0 | 23 | 3 | 23 | 22 | 23 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fall | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
| |
| Skin laceration | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
| |
| Myelitis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Cervical vertebral fracture | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
| |
| Chest injury | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
| |
| Concussion | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
| |
| Meningitis chemical | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
| |
| Rib fracture | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
| |
| Spinal column injury | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
| |
| Thoracic vertebral fracture | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Hemiparesis | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Hydrocephalus | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Hyporeflexia | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Neuritis | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Radiculopathy | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Completed suicide | Psychiatric disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Suicide attempt | Psychiatric disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vertigo | Ear and labyrinth disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Gait disturbance | General disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Injection site pain | General disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Puncture site pain | General disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Ear infection | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
| |
| Head injury | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
| |
| Ligament sprain | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
| |
| Limb injury | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
| |
| Post lumbar puncture syndrome | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
| |
| Procedural headache | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
| |
| Procedural pain | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
| |
| Skin abrasion | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
| |
| Skin laceration | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
| |
| CSF protein increased | Investigations | MedDRA 22.1 | Systematic Assessment |
| |
| CSF white blood cell count increased | Investigations | MedDRA 22.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Balance disorder | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Cerebral ventricle dilatation | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Dysarthria | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Dyskinesia | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Hyperkinesia | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Lumbar radiculopathy | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Motor dysfunction | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Parkinsonism | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Presyncope | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Syncope | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Depressed mood | Psychiatric disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 22.1 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA 22.1 | Systematic Assessment |
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| Irritability | Psychiatric disorders | MedDRA 22.1 | Systematic Assessment |
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| Tension | Psychiatric disorders | MedDRA 22.1 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA 22.1 | Systematic Assessment |
|
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Hoffmann-La Roche | 800 821-8590 | genentech@druginfo.com |
| Oct 7, 2020 |
| Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D006816 | Huntington Disease |
| ID | Term |
|---|---|
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D003704 | Dementia |
| D002819 | Chorea |
| D020820 | Dyskinesias |
| D009069 | Movement Disorders |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| C000718631 | tominersen |
Not provided
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| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Other |
|
|
|
|
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
|