Huntington Disease
Conditions
Brief summary
This study will evaluate the long-term safety and tolerability of RO7234292 (RG6042) in participants who have completed other F. Hoffmann-La Roche, Ltd.-sponsored and/or Genentech-sponsored studies in the Huntington's disease (HD) in the development program for RG6042.
Detailed description
Entry into the study should occur at the time the participant completes participation in one of the preceding studies. Upon completion of the inclusion visit, eligible participants will receive either RO7234292 (RG6042) every 8 weeks (Q8W) or RO7234292 (RG6042) every 16 weeks (Q16W) by the bolus intrathecal injection.
Interventions
Intrathecal injection
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
25 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Prior enrollment in a Roche-sponsored or Genentech-sponsored study in HD for the RO7234292 (RG6042) development program that made provision for entry into an OLE study * For women of childbearing potential: agreement to remain abstinent or use contraceptive measures * For men: agreement to remain abstinent or use a condom, and agreement to refrain from donating sperm * Patients who were screened and eligible for the placebo-controlled Phase III Study BN40423 but could not be randomized prior to the close of Study BN40423 enrollment due to challenges relating to the COVID-19 pandemic Inclusion criteria of patients who were screened and eligible for the placebo-controlled Phase III Study BN40423 but could not be randomized prior to the close of Study BN40423 enrollment due to challenges relating to the COVID-19 pandemic: * Manifest HD diagnosis, defined as a DCL score of 4 * Independence Scale (IS) score \>=70 * Genetically confirmed disease by direct DNA testing with a CAP score \>400 * Clinical assessment to ensure individual has intact functional independence at baseline to maintain self-care and core activities of daily living (ADLs).
Exclusion criteria
* Withdrawal of consent from the preceding study * Permanent discontinuation of RO7234292 (RG6042) for any drug-related safety concern during the preceding study or meeting of any study treatment discontinuation criteria specified in the preceding study at the time of enrollment into this study * An ongoing, unresolved, clinically significant medical problem that in the judgment of the investigator would make it unsafe for the patient to participate in this study * Antiplatelet or anticoagulant therapy within 14 days prior to inclusion or anticipated use during the study, including, but not limited to, aspirin, clopidogrel, dipyridamole, warfarin, dabigatran, rivaroxaban, and apixaban * History of bleeding diathesis or coagulopathy * Platelet count less than the lower limit of normal * Concurrent participation in any therapeutic clinical trial * Study treatment (RO7234292/RG6042) is commercially marketed in the patient's country for the patient-specific disease and is accessible to the patient * Pregnant or breastfeeding, or intending to become pregnant during the study or within 5 months after the final dose of study drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Treatment Emergent Adverse Events | Up to Approximately 3 Years | The reported are the treatment-emergent AEs with an onset date up to 5 months after last study drug intake. |
| Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Up to approximately 3 Years | C-SSRS is to assess suicidal ideation and behavior. 4 constructs measured: severity of ideation, intensity of ideation, behavior, and lethality of actual suicide attempts. Yes/No data collected for 10 categories, composite endpoints based on the categories are followed over time to monitor safety. Composite endpoint of suicidal ideation (1-5), n and (%) are the number and % of who experience any of the five suicidal ideation events at least once after receiving the first dose of study medication. Composite endpoint of suicidal behavior (6-10), n and (%) are the number and percent of patients who experience any 1of 5 suicidal behavior events at least 1 after receiving the 5 dose of study medication. Composite endpoint of suicidal ideation or behavior (1-10), n and (%) are the number and % of patients who experience any 1 the 10 suicidal ideation or behavior events at least once after receiving the first dose of study medication. |
| Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | Up to Approximately 3 Years | MoCA contains a series of basic assessments, including attention and visuospatial tasks. The total score ranges from 0-30, where lower scores indicate greater impairment. MOCA01-Total scores are reported. The data presented are absolute scores for baseline and change from baseline for post-baseline assessments. All Arms except Tominersen 120mg Q4W (Period 1) belong to the Milestone Period 2. |
Countries
Austria, Canada, Germany, Italy, Netherlands, Spain, United Kingdom, United States
Participant flow
Recruitment details
The study consists of Period 1 and 2. All participants (17) in the Q4W arm stopped Q4W dosing (Period 1) and 15 participants continued into the two Arms of Period 2. Due to the statistical outputs available, Period 1 and 2 are reported as Milestones below. None of the participants completed the study.
Pre-assignment details
Periods 1 and 2 are sequential. 15 from 17 participants from Period 1 Q4W were re-randomized to receive Tominersen 120 mg Q8W or Q16W in Period 2 randomly and blinded. .
Participants by arm
| Arm | Count |
|---|---|
| Tominersen 120mg Q4W Participants received open-label RO7234292 Q4W in this Arm | 17 |
| Tominersen 120mg Q8W Participants received open-label RO7234292 Q8W in this Arm | 138 |
| Tominersen 120mg Q16W Participants received open-label RO7234292 Q16W in this Arm | 81 |
| Total | 236 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 0 |
| Overall Study | Death | 1 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 2 | 0 |
| Overall Study | Participant declined follow-up visit | 0 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 3 | 0 |
| Overall Study | Pregnancy | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 1 | 0 |
| Overall Study | Sponsor's decision | 12 | 99 | 61 |
| Overall Study | Withdrawal by Subject | 3 | 30 | 18 |
Baseline characteristics
| Characteristic | Tominersen 120mg Q4W | Total | Tominersen 120mg Q8W | Tominersen 120mg Q16W |
|---|---|---|---|---|
| Age, Continuous Period 1 | 50.4 Years STANDARD_DEVIATION 8.9 | 50.4 Years STANDARD_DEVIATION 8.9 | — | — |
| Age, Continuous Period 2 | — | 48.2 Years STANDARD_DEVIATION 10.5 | 47.9 Years STANDARD_DEVIATION 9.8 | 48.4 Years STANDARD_DEVIATION 11.2 |
| Ethnicity (NIH/OMB) Period 1 Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Period 1 Not Hispanic or Latino | 17 Participants | 17 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Period 1 Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Period 2 Hispanic or Latino | 0 Participants | 20 Participants | 13 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Period 2 Not Hispanic or Latino | 0 Participants | 199 Participants | 125 Participants | 74 Participants |
| Ethnicity (NIH/OMB) Period 2 Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Period 1 American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Period 1 Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Period 1 Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Period 1 More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Period 1 Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Period 1 Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Period 1 White | 17 Participants | 17 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Period 2 American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Period 2 Asian | 0 Participants | 3 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Period 2 Black or African American | 0 Participants | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Period 2 More than one race | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Period 2 Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Period 2 Unknown or Not Reported | 0 Participants | 4 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Period 2 White | 0 Participants | 208 Participants | 132 Participants | 76 Participants |
| Sex: Female, Male Period 1 Female | 6 Participants | 6 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Period 1 Male | 11 Participants | 11 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Period 2 Female | 0 Participants | 108 Participants | 71 Participants | 37 Participants |
| Sex: Female, Male Period 2 Male | 0 Participants | 111 Participants | 67 Participants | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 14 | 0 / 143 | 1 / 88 |
| other Total, other adverse events | 12 / 14 | 99 / 143 | 56 / 88 |
| serious Total, serious adverse events | 1 / 14 | 17 / 143 | 9 / 88 |
Outcome results
Primary
Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA)
MoCA contains a series of basic assessments, including attention and visuospatial tasks. The total score ranges from 0-30, where lower scores indicate greater impairment. MOCA01-Total scores are reported. The data presented are absolute scores for baseline and change from baseline for post-baseline assessments. All Arms except Tominersen 120mg Q4W (Period 1) belong to the Milestone Period 2.
Time frame: Up to Approximately 3 Years
Population: Safety Population. Data evaluable participants were reported, all other data are not available. Only those participants who contributed and whose data were analyzed for data are reported in the table.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tominersen 120mg Q4W | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Baseline | 24.50 Score of a Scale | Standard Deviation 3.98 |
| Tominersen 120mg Q4W | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 33 | 3.00 Score of a Scale | — |
| Tominersen 120mg Q4W | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 25 | 3.00 Score of a Scale | — |
| Tominersen 120mg Q4W | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 17 | -4.00 Score of a Scale | — |
| Tominersen 120 mg Q8W | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 129 | -0.75 Score of a Scale | Standard Deviation 1.22 |
| Tominersen 120 mg Q8W | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 65 | -0.09 Score of a Scale | Standard Deviation 2.09 |
| Tominersen 120 mg Q8W | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 17 | 0.46 Score of a Scale | Standard Deviation 2.19 |
| Tominersen 120 mg Q8W | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 145 | 0.33 Score of a Scale | Standard Deviation 1.53 |
| Tominersen 120 mg Q8W | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 97 | -0.47 Score of a Scale | Standard Deviation 2.06 |
| Tominersen 120 mg Q8W | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 49 | 0.33 Score of a Scale | Standard Deviation 2.33 |
| Tominersen 120 mg Q8W | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 81 | 0.59 Score of a Scale | Standard Deviation 1.3 |
| Tominersen 120 mg Q8W | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Baseline | 25.08 Score of a Scale | Standard Deviation 3.49 |
| Tominersen 120 mg Q8W | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 113 | 0.18 Score of a Scale | Standard Deviation 1.94 |
| Tominersen 120 mg Q8W | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 33 | 0.16 Score of a Scale | Standard Deviation 1.74 |
| Tominersen 120 mg Q16W | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 17 | 0.16 Score of a Scale | Standard Deviation 2.58 |
| Tominersen 120 mg Q16W | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 49 | -0.39 Score of a Scale | Standard Deviation 2.83 |
| Tominersen 120 mg Q16W | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 97 | -0.97 Score of a Scale | Standard Deviation 3.12 |
| Tominersen 120 mg Q16W | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 129 | -0.50 Score of a Scale | Standard Deviation 1.95 |
| Tominersen 120 mg Q16W | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 81 | -0.38 Score of a Scale | Standard Deviation 3.31 |
| Tominersen 120 mg Q16W | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Baseline | 24.92 Score of a Scale | Standard Deviation 3.47 |
| Tominersen 120 mg Q16W | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 65 | -0.08 Score of a Scale | Standard Deviation 2.56 |
| Tominersen 120 mg Q16W | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 33 | 0.28 Score of a Scale | Standard Deviation 2.61 |
| Tominersen 120 mg Q16W | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 113 | -0.36 Score of a Scale | Standard Deviation 2.65 |
| Tominersen 120mg Q8W (With Loading) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 81 | -0.09 Score of a Scale | Standard Deviation 1.95 |
| Tominersen 120mg Q8W (With Loading) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 113 | 0.10 Score of a Scale | Standard Deviation 2.62 |
| Tominersen 120mg Q8W (With Loading) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 17 | 0.19 Score of a Scale | Standard Deviation 2.56 |
| Tominersen 120mg Q8W (With Loading) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 145 | -4.83 Score of a Scale | Standard Deviation 5.91 |
| Tominersen 120mg Q8W (With Loading) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 33 | 0.35 Score of a Scale | Standard Deviation 1.76 |
| Tominersen 120mg Q8W (With Loading) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 49 | -0.08 Score of a Scale | Standard Deviation 2.26 |
| Tominersen 120mg Q8W (With Loading) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 65 | -0.08 Score of a Scale | Standard Deviation 1.91 |
| Tominersen 120mg Q8W (With Loading) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Baseline | 24.62 Score of a Scale | Standard Deviation 4.44 |
| Tominersen 120mg Q8W (With Loading) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 129 | -0.15 Score of a Scale | Standard Deviation 3.48 |
| Tominersen 120mg Q8W (With Loading) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 97 | 0.45 Score of a Scale | Standard Deviation 2.2 |
| Tominersen 120mg Q8W (Prior BP40410) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 81 | -2.00 Score of a Scale | — |
| Tominersen 120mg Q8W (Prior BP40410) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 17 | -1.00 Score of a Scale | Standard Deviation 1 |
| Tominersen 120mg Q8W (Prior BP40410) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 49 | -0.67 Score of a Scale | Standard Deviation 3.06 |
| Tominersen 120mg Q8W (Prior BP40410) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 65 | -5.00 Score of a Scale | — |
| Tominersen 120mg Q8W (Prior BP40410) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Baseline | 25.33 Score of a Scale | Standard Deviation 1.53 |
| Tominersen 120mg Q8W (Prior BP40410) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 33 | 0.67 Score of a Scale | Standard Deviation 2.08 |
| Tominersen 120mg Q16W (Prior Q4W) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 97 | 0.24 Score of a Scale | Standard Deviation 2.46 |
| Tominersen 120mg Q16W (Prior Q4W) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 81 | 0.25 Score of a Scale | Standard Deviation 2.57 |
| Tominersen 120mg Q16W (Prior Q4W) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 49 | -0.40 Score of a Scale | Standard Deviation 2.68 |
| Tominersen 120mg Q16W (Prior Q4W) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 33 | -0.90 Score of a Scale | Standard Deviation 2.76 |
| Tominersen 120mg Q16W (Prior Q4W) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 129 | -0.11 Score of a Scale | Standard Deviation 1.9 |
| Tominersen 120mg Q16W (Prior Q4W) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 17 | -0.57 Score of a Scale | Standard Deviation 2.01 |
| Tominersen 120mg Q16W (Prior Q4W) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 65 | -0.43 Score of a Scale | Standard Deviation 2.86 |
| Tominersen 120mg Q16W (Prior Q4W) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 113 | 0.19 Score of a Scale | Standard Deviation 2.51 |
| Tominersen 120mg Q16W (Prior Q4W) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Baseline | 23.43 Score of a Scale | Standard Deviation 4.49 |
| Tominersen 120mg Q16W (Prior Q4W) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 145 | 0.00 Score of a Scale | — |
| Tominersen 120mg Q16W (No Loading) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 33 | 0.32 Score of a Scale | Standard Deviation 2.44 |
| Tominersen 120mg Q16W (No Loading) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Baseline | 24.03 Score of a Scale | Standard Deviation 3.88 |
| Tominersen 120mg Q16W (No Loading) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 17 | -0.17 Score of a Scale | Standard Deviation 2.79 |
| Tominersen 120mg Q16W (No Loading) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 49 | -0.13 Score of a Scale | Standard Deviation 2.53 |
| Tominersen 120mg Q16W (No Loading) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 65 | 0.27 Score of a Scale | Standard Deviation 2.85 |
| Tominersen 120mg Q16W (No Loading) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 81 | -0.24 Score of a Scale | Standard Deviation 2.9 |
| Tominersen 120mg Q16W (No Loading) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 97 | -0.46 Score of a Scale | Standard Deviation 3.01 |
| Tominersen 120mg Q16W (No Loading) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 113 | 0.36 Score of a Scale | Standard Deviation 3.01 |
| Tominersen 120mg Q16W (No Loading) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 129 | 2.20 Score of a Scale | Standard Deviation 3.19 |
| Tominersen 120mg Q16W (Prior BP40410) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 65 | 0.50 Score of a Scale | Standard Deviation 3.54 |
| Tominersen 120mg Q16W (Prior BP40410) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 49 | 3.00 Score of a Scale | Standard Deviation 3.46 |
| Tominersen 120mg Q16W (Prior BP40410) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Baseline | 19.75 Score of a Scale | Standard Deviation 4.35 |
| Tominersen 120mg Q16W (Prior BP40410) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 33 | 2.25 Score of a Scale | Standard Deviation 2.22 |
| Tominersen 120mg Q16W (Prior BP40410) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 17 | 3.25 Score of a Scale | Standard Deviation 2.36 |
| Tominersen 120mg Q16W (Prior BP40410) | Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA) | MOCA01-Total Week 81 | 0.50 Score of a Scale | Standard Deviation 3.54 |
Primary
Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS)
C-SSRS is to assess suicidal ideation and behavior. 4 constructs measured: severity of ideation, intensity of ideation, behavior, and lethality of actual suicide attempts. Yes/No data collected for 10 categories, composite endpoints based on the categories are followed over time to monitor safety. Composite endpoint of suicidal ideation (1-5), n and (%) are the number and % of who experience any of the five suicidal ideation events at least once after receiving the first dose of study medication. Composite endpoint of suicidal behavior (6-10), n and (%) are the number and percent of patients who experience any 1of 5 suicidal behavior events at least 1 after receiving the 5 dose of study medication. Composite endpoint of suicidal ideation or behavior (1-10), n and (%) are the number and % of patients who experience any 1 the 10 suicidal ideation or behavior events at least once after receiving the first dose of study medication.
Time frame: Up to approximately 3 Years
Population: Safety Population. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) are included. All other data were not evaluable due to participants' discontinuation
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tominersen 120mg Q4W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation (1-5) -Active Suicidal Ideation with Specific Plan and Intent | 0 Number of participants |
| Tominersen 120mg Q4W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation (1-5) -Non-specific Active Suicidal Thoughts | 0 Number of participants |
| Tominersen 120mg Q4W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation (1-5) -Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act | 0 Number of participants |
| Tominersen 120mg Q4W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation (1-5) -Active Suicidal Ideation with Intent to Act, without Specific Plan | 0 Number of participants |
| Tominersen 120mg Q4W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation (1-5) -Wish to Be Dead | 1 Number of participants |
| Tominersen 120mg Q4W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Behavior (6-10) -Preparatory Acts or Behavior | 0 Number of participants |
| Tominersen 120mg Q4W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Behavior (6-10) -Aborted Attempt | 0 Number of participants |
| Tominersen 120mg Q4W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Behavior (6-10) -Interrupted Attempt | 0 Number of participants |
| Tominersen 120mg Q4W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Behavior (6-10) -Non-fatal Suicide Attempt | 0 Number of participants |
| Tominersen 120mg Q4W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Behavior (6-10) -Completed Suicide | 0 Number of participants |
| Tominersen 120mg Q4W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation or Behavior (1-10) | 1 Number of participants |
| Tominersen 120mg Q4W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Self-injurious Behavior without Suicidal Intent | 0 Number of participants |
| Tominersen 120mg Q4W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Treatment-Emergent Suicidal Ideation | 0 Number of participants |
| Tominersen 120mg Q4W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Treatment-Emergent Serious Suicidal Ideation | 0 Number of participants |
| Tominersen 120mg Q4W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Emergence of Serious Suicidal Ideation | 0 Number of participants |
| Tominersen 120mg Q4W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Emergence of Suicidal Behavior | 0 Number of participants |
| Tominersen 120 mg Q8W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Behavior (6-10) -Preparatory Acts or Behavior | 1 Number of participants |
| Tominersen 120 mg Q8W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Behavior (6-10) -Aborted Attempt | 0 Number of participants |
| Tominersen 120 mg Q8W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Behavior (6-10) -Interrupted Attempt | 1 Number of participants |
| Tominersen 120 mg Q8W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Treatment-Emergent Serious Suicidal Ideation | 3 Number of participants |
| Tominersen 120 mg Q8W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Behavior (6-10) -Non-fatal Suicide Attempt | 2 Number of participants |
| Tominersen 120 mg Q8W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Behavior (6-10) -Completed Suicide | 0 Number of participants |
| Tominersen 120 mg Q8W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Emergence of Suicidal Behavior | 3 Number of participants |
| Tominersen 120 mg Q8W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation or Behavior (1-10) | 16 Number of participants |
| Tominersen 120 mg Q8W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation (1-5) -Wish to Be Dead | 16 Number of participants |
| Tominersen 120 mg Q8W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Emergence of Serious Suicidal Ideation | 2 Number of participants |
| Tominersen 120 mg Q8W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation (1-5) -Non-specific Active Suicidal Thoughts | 9 Number of participants |
| Tominersen 120 mg Q8W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Self-injurious Behavior without Suicidal Intent | 1 Number of participants |
| Tominersen 120 mg Q8W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation (1-5) -Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act | 7 Number of participants |
| Tominersen 120 mg Q8W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation (1-5) -Active Suicidal Ideation with Intent to Act, without Specific Plan | 3 Number of participants |
| Tominersen 120 mg Q8W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation (1-5) -Active Suicidal Ideation with Specific Plan and Intent | 2 Number of participants |
| Tominersen 120 mg Q8W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Treatment-Emergent Suicidal Ideation | 14 Number of participants |
| Tominersen 120 mg Q16W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation or Behavior (1-10) | 3 Number of participants |
| Tominersen 120 mg Q16W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Behavior (6-10) -Preparatory Acts or Behavior | 0 Number of participants |
| Tominersen 120 mg Q16W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Treatment-Emergent Suicidal Ideation | 2 Number of participants |
| Tominersen 120 mg Q16W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation (1-5) -Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act | 1 Number of participants |
| Tominersen 120 mg Q16W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Behavior (6-10) -Aborted Attempt | 0 Number of participants |
| Tominersen 120 mg Q16W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Emergence of Suicidal Behavior | 0 Number of participants |
| Tominersen 120 mg Q16W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation (1-5) -Wish to Be Dead | 3 Number of participants |
| Tominersen 120 mg Q16W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Behavior (6-10) -Interrupted Attempt | 0 Number of participants |
| Tominersen 120 mg Q16W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Self-injurious Behavior without Suicidal Intent | 0 Number of participants |
| Tominersen 120 mg Q16W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation (1-5) -Active Suicidal Ideation with Specific Plan and Intent | 0 Number of participants |
| Tominersen 120 mg Q16W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Behavior (6-10) -Non-fatal Suicide Attempt | 0 Number of participants |
| Tominersen 120 mg Q16W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Treatment-Emergent Serious Suicidal Ideation | 1 Number of participants |
| Tominersen 120 mg Q16W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation (1-5) -Non-specific Active Suicidal Thoughts | 1 Number of participants |
| Tominersen 120 mg Q16W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Behavior (6-10) -Completed Suicide | 0 Number of participants |
| Tominersen 120 mg Q16W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation (1-5) -Active Suicidal Ideation with Intent to Act, without Specific Plan | 1 Number of participants |
| Tominersen 120 mg Q16W | Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Emergence of Serious Suicidal Ideation | 1 Number of participants |
Primary
Percentage of Participants With Treatment Emergent Adverse Events
The reported are the treatment-emergent AEs with an onset date up to 5 months after last study drug intake.
Time frame: Up to Approximately 3 Years
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tominersen 120mg Q4W | Percentage of Participants With Treatment Emergent Adverse Events | 71.4 Percentage of Participants |
| Tominersen 120 mg Q8W | Percentage of Participants With Treatment Emergent Adverse Events | 83.9 Percentage of Participants |
| Tominersen 120 mg Q16W | Percentage of Participants With Treatment Emergent Adverse Events | 81.8 Percentage of Participants |