Alzheimer's Disease
Conditions
Keywords
Alzheimer Disease, Brain Diseases, Dementia, Neurodegenerative Diseases, Neurocognitive Disorders
Brief summary
This was a phase II, randomized, placebo-controlled, double-blind study to evaluate the efficacy and safety of Semorinemab in participants with prodromal to mild Alzheimer's disease. An optional 96-week open-label extension period was available to participants who completed the double-blind treatment period and who, in the judgment of the investigator, would potentially benefit from open-label Semorinemab treatment.
Interventions
DRUGSemorinemab
Participants will receive Semorinemab intravenously (IV).
DRUGPlacebo
Matching placebo doses of Semorinemab given intravenously (IV).
DRUG[18F]GTP1
\[18F\]GTP1 will be administered as a solution for intravenous (IV) use, as part of positron emission tomography (PET) imaging.
Sponsors
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Additional blinded personnel will include study site personnel who will evaluate participant status, contract research organization (CRO) personnel who will review case report forms (CRFs), and other sponsor agents (with the exception of the interactive voice or web-based response system \[IxRS\] vendor).
Eligibility
Sex/Gender
ALL
Age
50 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age between 50 and 80 years * National Institute on Aging/Alzheimer's Association core clinical criteria for probable Alzheimer's disease (AD) dementia or mild cognitive impairment (prodromal AD) * Evidence of the AD pathological process, by a positive amyloid assessment either on cerebrospinal fluid Aβ1-42 OR amyloid positron emission tomography (PET) scan. Historical amyloid PET scans may be accepted in some cases * Mild AD symptomatology, as defined by a screening Mini-Mental State Examination score of \>= 20 points and Clinical Dementia Rating (CDR) -Global Score of 0.5 or 1 * Abnormal memory function at screening * Availability of a person with sufficient contact with the participant to be able to provide accurate information on the participant's cognitive and functional ability
Exclusion criteria
* Pregnant or breastfeeding * Inability to tolerate magnetic resonance imaging (MRI) procedures or contraindication to MRI * Contraindications to both PET imaging and lumbar dural puncture (must be able to undergo at least one of these procedures to be eligible) * Residence in a skilled nursing facility * Any serious medical condition or abnormality in clinical laboratory tests that remains abnormal on retest and, in the investigator's judgment, precludes the patient's safe participation in and completion of the study, or bias the assessment of the clinical or mental status of the participant to a significant degree * Any evidence of a condition other than AD that may affect cognition * Alcohol or substance abuse within the past 2 years * Use of any experimental therapy within 90 days or 5 half-lives prior to screening, whichever is greater and any passive immunotherapy (immunoglobulin) against tau, except use of RO7105705 in Genentech Study GN39058, as long as the last dose was at least 90 days prior to screening * Use of any passive immunotherapy (immunoglobulin) against Aβ, unless the last dose was at least 1 year prior to screening and any active immunotherapy (vaccine) that is under evaluation to prevent or postpone cognitive decline * Any previous treatment with medications specifically intended to treat Parkinsonian symptoms or any other neurodegenerative disorder within 1 year of screening * Systemic immunosuppressive therapy within 12 months of screening through the entire study period * Typical antipsychotic or neuroleptic medication within 6 months of screening * Daily treatment with any of the following classes of medication, except for intermittent short-term use, which is permitted except within 2 days or 5 half-lives (whichever is longer) prior to any COA: atypical antipsychotics, opiates or opioids, benzodiazepines, barbiturates, hypnotics, or any medication with clinically significant centrally-acting antihistamine or anticholinergic activity * Stimulant medications, unless the dose has been stable within the 6 months prior to screening and is expected to be stable throughout the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline on the CDR-SB | Baseline and 73 Weeks | The Clinical Dementia Rating-Sum of Boxes (CDR-SB) rates impairment in 6 categories (memory, orientation, judgement and problem solving, community affairs, home and hobbies and personal care) on a 5-point scale in which no impairment = 0, questionable impairment = 0.5 and mild, moderate and severe impairment = 1, 2 and 3 respectively. The score range is from 0 to 18 with a high score indicating a high disease severity. The difference in mean change from Baseline to Week 73 between Semorinemab doses and Placebo treated participants was estimated. The difference in mean change from Baseline to Week 73 between Semorinemab doses and Placebo treated participants was estimated. |
| Percentage of Participants With Adverse Events | Up to the data cutoff date 15 January 2021 (up to approximately 39 months) | Percentage of participants with at least one adverse event |
| Change From Baseline on the C-SSRS | Baseline to data cutoff date 15 January 2021 (up to approximately 39 months) | Categories are as defined in the Classification Algorithm for Suicide Assessment (CASA) based on the Columbia Suicide Severity Rating Scale (C-SSRS) questionnaire. SI1: Passive category is Wish to be dead, SI2: Active-Nonspecific (no method, intent or plan), SI3: Active-Method, but no intent or Plan, SI4: Active-Method and intent, but no plan in C-SSRS. The worst post-baseline suicidal ideation is the highest across post-baseline visits, with highest as SI5 and lowest as SI1. Percentages are based on the total number of subjects in a treatment group. Baseline is the last observation prior to initiation of study drug. |
| Other Abnormal MRI Findings | Baseline, Week 9, Week 49, Week 73, Study Treatment Discontinuation, and Week 89 | Other abnormal MRI findings by visit. For the Double Blind Period, baseline is defined as last results prior to initiation of study drug. For the Open Label Extension Period, baseline is defined as last results prior to entering the open label period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Concentrations of Semorinemab at Specified Timepoints | Up to 109 weeks | Serum concentrations of Semorinemab at specified timepoints. |
| Change From Baseline on the Repeatable Battery for Assessment of Neuropsychological Status (RBANS) | Baseline and 73 weeks | The RBANS is a validated neuropsychological assessment has been shown to be a useful tool in both clinical and research settings. The RBANS consists of ten subtests that are combined to provide five indices, one for each of the five domains tested (immediate memory, visuospatial/constructional, language, attention, and delayed memory). Scores range from 40 to 160 and a higher score indicates better cognitive functioning. A decrease in the outcome measure from baseline corresponds to disease worsening. The difference in mean change from Baseline to Week 73 between Semorinemab doses and Placebo treated participants was estimated. |
| Presence of Anti-drug Antibodies During the Study Relative to Their Presence at Baseline | Up to 109 weeks | Presence of anti-drug antibodies during the study relative to their presence at baseline. |
| Change From Baseline on the Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog-13) Subscale Score | Baseline and 73 weeks | The ADAS-Cog-13 assesses multiple cognitive domains including memory, comprehension, praxis, orientation, and spontaneous speech. Most of these are assessed by tests although some are rated by the clinician on a 5-point scale. The ADAS-Cog-13 is the ADAS-Cog-11 with 2 further items: delayed word recall and total digit cancellation. The score range for ADAS-Cog-13 is from 0 to 85 with high scores representing severe dysfunction. The difference in mean change from Baseline to Week 73 between Semorinemab doses and Placebo treated participants was estimated. |
| Change From Baseline on the Amsterdam Instrumental Activity of Daily Living (iADL) Questionnaire | Baseline and 73 weeks | The Amsterdam iADL questionnaire is an informant-based instrument for measuring iADL problems in participants with dementia. This instrument consists of 70 items, scored on a 5-point scale, that uses item response theory for scoring. Items presented to the informant are tailored to responses to earlier items; thus each administration of the Amsterdam iADL may consist of less than the total of 70 items. The resulting score ranges from 20 to 80 with lower scores indicating poorer performance. A decrease in the outcome measure from baseline corresponds to disease worsening. The difference in mean change from Baseline to Week 73 between Semorinemab doses and Placebo treated participants was estimated. |
| Change From Baseline on the Alzheimer's Disease Cooperative Study Group-Activities of Daily Living Inventory | Baseline and 73 weeks | The ADCS-ADL (Alzheimer's Disease Cooperative Study-Activities of Daily Living) is the scale most widely used to assess functional outcomes in participants with AD. The ADCS-ADL covers both basic ADL (e.g., eating and toileting) and more complex 'instrumental' ADL or iADL (e.g., using the telephone, managing finances and preparing a meal). The ADCS-ADL consists of 23 questions with a score range of 0 to 78 where a higher score represents better function. The difference in mean change from Baseline to Week 73 between Semorinemab doses and Placebo treated participants was estimated. |
Countries
Australia, Belgium, Canada, Denmark, France, Germany, Italy, Netherlands, Poland, Spain, Sweden, United Kingdom, United States
Participant flow
Pre-assignment details
The study consisted of a double-blind treatment period and an optional open-label extension (OLE) period. OLE period was available to participants who completed the double-blind treatment period and who, in the judgment of the investigator, would potentially benefit from open-label semorinemab treatment.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Double Blind Period Matching placebo dose of Semorinemab was administered intravenously in the double-blind treatment period. | 135 |
| Dose 1 Semorinemab Double Blind Period Semorinemab was administered intravenously at dose 1 in the double-blind treatment period. | 94 |
| Dose 2 Semorinemab Double Blind Period Semorinemab was administered intravenously at dose 2 in the double-blind treatment period. | 136 |
| Dose 3 Semorinemab Double Blind Period Semorinemab was administered intravenously at dose 3 in the double-blind treatment period. | 92 |
| Total | 457 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Absence of Consistent and Reliable Caregiver | 0 | 0 | 0 | 1 |
| Overall Study | Adverse Event | 10 | 7 | 6 | 5 |
| Overall Study | Caregiver and Participant Withdrew Consent | 0 | 0 | 1 | 0 |
| Overall Study | Caregiver Passed Away | 1 | 0 | 0 | 0 |
| Overall Study | Caregiver Passed Away & Family Moved Out of State | 0 | 0 | 1 | 0 |
| Overall Study | Caregiver Unavailability | 1 | 1 | 0 | 0 |
| Overall Study | Death | 2 | 0 | 2 | 1 |
| Overall Study | Drug Interrupted for Too Long Due to Prohibited Med | 0 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 2 | 1 | 1 | 0 |
| Overall Study | Medical Monitor Decision | 1 | 0 | 0 | 0 |
| Overall Study | Participant No Longer Has Study Partner | 0 | 0 | 0 | 1 |
| Overall Study | Participant Non-Compliance | 0 | 0 | 1 | 0 |
| Overall Study | Participant Non Compliance With Concomitant Medications | 0 | 0 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 2 | 2 | 2 |
| Overall Study | Protocol Deviation | 2 | 1 | 3 | 1 |
| Overall Study | Research Department Closure | 0 | 0 | 1 | 0 |
| Overall Study | Study Terminated By Sponsor | 101 | 75 | 100 | 69 |
| Overall Study | Withdrawal by Caregiver | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 14 | 6 | 14 | 12 |
Baseline characteristics
| Characteristic | Placebo Double Blind Period | Dose 1 Semorinemab Double Blind Period | Dose 2 Semorinemab Double Blind Period | Dose 3 Semorinemab Double Blind Period | Total |
|---|---|---|---|---|---|
| Age, Continuous | 69.7 Year STANDARD_DEVIATION 7.3 | 70.2 Year STANDARD_DEVIATION 6.7 | 69.3 Year STANDARD_DEVIATION 7.1 | 69.6 Year STANDARD_DEVIATION 6.7 | 69.6 Year STANDARD_DEVIATION 6.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 4 Participants | 5 Participants | 3 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 126 Participants | 80 Participants | 125 Participants | 79 Participants | 410 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 8 Participants | 10 Participants | 6 Participants | 10 Participants | 34 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 6 Participants | 5 Participants | 9 Participants | 24 Participants |
| Race (NIH/OMB) White | 129 Participants | 83 Participants | 128 Participants | 82 Participants | 422 Participants |
| Sex: Female, Male Female | 75 Participants | 51 Participants | 79 Participants | 48 Participants | 253 Participants |
| Sex: Female, Male Male | 60 Participants | 43 Participants | 57 Participants | 44 Participants | 204 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 130 | 0 / 89 | 1 / 132 | 1 / 90 | 1 / 360 |
| other Total, other adverse events | 76 / 130 | 57 / 89 | 88 / 132 | 60 / 90 | 76 / 360 |
| serious Total, serious adverse events | 14 / 130 | 17 / 89 | 17 / 132 | 16 / 90 | 17 / 360 |
Outcome results
Primary
Change From Baseline on the CDR-SB
The Clinical Dementia Rating-Sum of Boxes (CDR-SB) rates impairment in 6 categories (memory, orientation, judgement and problem solving, community affairs, home and hobbies and personal care) on a 5-point scale in which no impairment = 0, questionable impairment = 0.5 and mild, moderate and severe impairment = 1, 2 and 3 respectively. The score range is from 0 to 18 with a high score indicating a high disease severity. The difference in mean change from Baseline to Week 73 between Semorinemab doses and Placebo treated participants was estimated. The difference in mean change from Baseline to Week 73 between Semorinemab doses and Placebo treated participants was estimated.
Time frame: Baseline and 73 Weeks
Population: Modified intent-to-treat (mITT) population included all randomized participants who received at least one dose of study drug and had at least one postbaseline primary efficacy Clinical Dementia Rating-Sum of Boxes (CDR-SB) measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Double Blind Period | Change From Baseline on the CDR-SB | 2.19 Units on a scale | Standard Error 0.226 |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the CDR-SB | 2.36 Units on a scale | Standard Error 0.268 |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the CDR-SB | 2.36 Units on a scale | Standard Error 0.222 |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the CDR-SB | 2.41 Units on a scale | Standard Error 0.27 |
p-value: 0.6147Mixed-effect Model Repeated Measures
p-value: 0.5778Mixed-effect Model Repeated Measures
p-value: 0.5136Mixed-effect Model Repeated Measures
Primary
Change From Baseline on the C-SSRS
Categories are as defined in the Classification Algorithm for Suicide Assessment (CASA) based on the Columbia Suicide Severity Rating Scale (C-SSRS) questionnaire. SI1: Passive category is Wish to be dead, SI2: Active-Nonspecific (no method, intent or plan), SI3: Active-Method, but no intent or Plan, SI4: Active-Method and intent, but no plan in C-SSRS. The worst post-baseline suicidal ideation is the highest across post-baseline visits, with highest as SI5 and lowest as SI1. Percentages are based on the total number of subjects in a treatment group. Baseline is the last observation prior to initiation of study drug.
Time frame: Baseline to data cutoff date 15 January 2021 (up to approximately 39 months)
Population: The safety-evaluable population included all participants who were randomly allocated and received at least one dose of study drug (MTAU9937A or placebo) during the double-blind treatment period with treatment groups defined according to actual treatment received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo Double Blind Period | Change From Baseline on the C-SSRS | SI2/SI4 | 0 Participants |
| Placebo Double Blind Period | Change From Baseline on the C-SSRS | Missing/No Events | 1 Participants |
| Placebo Double Blind Period | Change From Baseline on the C-SSRS | SI4/SI1 | 0 Participants |
| Placebo Double Blind Period | Change From Baseline on the C-SSRS | SI1/SI3 | 0 Participants |
| Placebo Double Blind Period | Change From Baseline on the C-SSRS | SI4/No Event | 0 Participants |
| Placebo Double Blind Period | Change From Baseline on the C-SSRS | SI3/Missing | 0 Participants |
| Placebo Double Blind Period | Change From Baseline on the C-SSRS | SI3/No Event | 1 Participants |
| Placebo Double Blind Period | Change From Baseline on the C-SSRS | SI3/SI4 | 0 Participants |
| Placebo Double Blind Period | Change From Baseline on the C-SSRS | Missing/SI2 | 0 Participants |
| Placebo Double Blind Period | Change From Baseline on the C-SSRS | SI1/No Event | 3 Participants |
| Placebo Double Blind Period | Change From Baseline on the C-SSRS | No Event/ Missing | 1 Participants |
| Placebo Double Blind Period | Change From Baseline on the C-SSRS | No Event/ SI4 | 0 Participants |
| Placebo Double Blind Period | Change From Baseline on the C-SSRS | Missing/SI1 | 0 Participants |
| Placebo Double Blind Period | Change From Baseline on the C-SSRS | SI3/SI3 | 0 Participants |
| Placebo Double Blind Period | Change From Baseline on the C-SSRS | SI3/SI2 | 0 Participants |
| Placebo Double Blind Period | Change From Baseline on the C-SSRS | SI3/SI1 | 0 Participants |
| Placebo Double Blind Period | Change From Baseline on the C-SSRS | SI2/Missing | 0 Participants |
| Placebo Double Blind Period | Change From Baseline on the C-SSRS | SI1/SI2 | 1 Participants |
| Placebo Double Blind Period | Change From Baseline on the C-SSRS | SI2/No Event | 0 Participants |
| Placebo Double Blind Period | Change From Baseline on the C-SSRS | SI1/Missing | 0 Participants |
| Placebo Double Blind Period | Change From Baseline on the C-SSRS | SI1/SI4 | 1 Participants |
| Placebo Double Blind Period | Change From Baseline on the C-SSRS | SI2/SI1 | 0 Participants |
| Placebo Double Blind Period | Change From Baseline on the C-SSRS | SI4/Missing | 0 Participants |
| Placebo Double Blind Period | Change From Baseline on the C-SSRS | No Event/SI3 | 0 Participants |
| Placebo Double Blind Period | Change From Baseline on the C-SSRS | Missing/Missing | 0 Participants |
| Placebo Double Blind Period | Change From Baseline on the C-SSRS | Missing/SI4 | 0 Participants |
| Placebo Double Blind Period | Change From Baseline on the C-SSRS | SI2/SI2 | 0 Participants |
| Placebo Double Blind Period | Change From Baseline on the C-SSRS | No Event/ SI2 | 0 Participants |
| Placebo Double Blind Period | Change From Baseline on the C-SSRS | No Event/SI1 | 3 Participants |
| Placebo Double Blind Period | Change From Baseline on the C-SSRS | No Event/No Event | 119 Participants |
| Placebo Double Blind Period | Change From Baseline on the C-SSRS | SI2/SI3 | 0 Participants |
| Placebo Double Blind Period | Change From Baseline on the C-SSRS | SI1/SI1 | 0 Participants |
| Placebo Double Blind Period | Change From Baseline on the C-SSRS | Missing/SI3 | 0 Participants |
| Placebo Double Blind Period | Change From Baseline on the C-SSRS | SI4/SI3 | 0 Participants |
| Placebo Double Blind Period | Change From Baseline on the C-SSRS | SI4/SI2 | 0 Participants |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI3/No Event | 0 Participants |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI4/Missing | 0 Participants |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | Missing/SI1 | 0 Participants |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | Missing/No Events | 1 Participants |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI2/No Event | 1 Participants |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI2/SI1 | 0 Participants |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI2/SI3 | 0 Participants |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI2/SI4 | 0 Participants |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI2/Missing | 0 Participants |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI3/SI1 | 0 Participants |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | Missing/SI2 | 0 Participants |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI3/SI2 | 0 Participants |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI3/SI4 | 0 Participants |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI3/Missing | 0 Participants |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI4/No Event | 0 Participants |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI4/SI1 | 0 Participants |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI4/SI2 | 0 Participants |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | Missing/SI3 | 0 Participants |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | Missing/Missing | 0 Participants |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | No Event/No Event | 80 Participants |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | No Event/SI1 | 3 Participants |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | No Event/ SI2 | 1 Participants |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | No Event/SI3 | 0 Participants |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | Missing/SI4 | 0 Participants |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI1/SI3 | 0 Participants |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI1/SI4 | 0 Participants |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI1/Missing | 0 Participants |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI2/SI2 | 0 Participants |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI3/SI3 | 0 Participants |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI4/SI3 | 0 Participants |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | No Event/ SI4 | 0 Participants |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | No Event/ Missing | 0 Participants |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI1/No Event | 3 Participants |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI1/SI1 | 0 Participants |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI1/SI2 | 0 Participants |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI4/Missing | 0 Participants |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI1/SI2 | 0 Participants |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI1/SI3 | 0 Participants |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | Missing/SI1 | 0 Participants |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI1/No Event | 1 Participants |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI4/SI1 | 0 Participants |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI1/SI4 | 0 Participants |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI4/SI3 | 0 Participants |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI2/Missing | 0 Participants |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI3/SI3 | 0 Participants |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | No Event/ SI2 | 1 Participants |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI2/SI3 | 0 Participants |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI1/Missing | 0 Participants |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI2/SI1 | 1 Participants |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI2/SI4 | 0 Participants |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | No Event/ SI4 | 0 Participants |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI1/SI1 | 0 Participants |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI2/SI2 | 0 Participants |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI2/No Event | 2 Participants |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | Missing/SI3 | 0 Participants |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | No Event/ Missing | 0 Participants |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | Missing/SI4 | 0 Participants |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | Missing/Missing | 0 Participants |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | Missing/SI2 | 0 Participants |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI3/SI4 | 0 Participants |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI4/No Event | 0 Participants |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | No Event/No Event | 123 Participants |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI4/SI2 | 0 Participants |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI3/SI2 | 0 Participants |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI3/No Event | 0 Participants |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI3/SI1 | 0 Participants |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | No Event/SI1 | 2 Participants |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | No Event/SI3 | 0 Participants |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI3/Missing | 0 Participants |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | Missing/No Events | 2 Participants |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI2/SI3 | 0 Participants |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI2/SI4 | 0 Participants |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI4/SI1 | 0 Participants |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | Missing/No Events | 0 Participants |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI4/SI2 | 0 Participants |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI4/No Event | 0 Participants |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI4/SI3 | 0 Participants |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI1/SI2 | 0 Participants |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI2/SI2 | 1 Participants |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | No Event/ Missing | 1 Participants |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | No Event/No Event | 83 Participants |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | Missing/SI1 | 0 Participants |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | Missing/SI3 | 0 Participants |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | Missing/SI4 | 0 Participants |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI2/SI1 | 0 Participants |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | Missing/Missing | 0 Participants |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | No Event/SI1 | 4 Participants |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | No Event/ SI2 | 0 Participants |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI1/No Event | 1 Participants |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI1/SI3 | 0 Participants |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI2/No Event | 0 Participants |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI3/SI2 | 0 Participants |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI1/Missing | 0 Participants |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI1/SI1 | 0 Participants |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI1/SI4 | 0 Participants |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI4/Missing | 0 Participants |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI3/SI4 | 0 Participants |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI3/No Event | 0 Participants |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI3/SI1 | 0 Participants |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | No Event/SI3 | 0 Participants |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI3/SI3 | 0 Participants |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | Missing/SI2 | 0 Participants |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI2/Missing | 0 Participants |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | SI3/Missing | 0 Participants |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the C-SSRS | No Event/ SI4 | 0 Participants |
| Dose 2 Semorinemab Open Label Extension Period | Change From Baseline on the C-SSRS | SI3/No Event | 1 Participants |
| Dose 2 Semorinemab Open Label Extension Period | Change From Baseline on the C-SSRS | SI2/SI3 | 0 Participants |
| Dose 2 Semorinemab Open Label Extension Period | Change From Baseline on the C-SSRS | Missing/SI4 | 0 Participants |
| Dose 2 Semorinemab Open Label Extension Period | Change From Baseline on the C-SSRS | SI3/SI2 | 0 Participants |
| Dose 2 Semorinemab Open Label Extension Period | Change From Baseline on the C-SSRS | SI2/SI1 | 2 Participants |
| Dose 2 Semorinemab Open Label Extension Period | Change From Baseline on the C-SSRS | SI3/SI4 | 0 Participants |
| Dose 2 Semorinemab Open Label Extension Period | Change From Baseline on the C-SSRS | Missing/SI2 | 0 Participants |
| Dose 2 Semorinemab Open Label Extension Period | Change From Baseline on the C-SSRS | Missing/SI3 | 0 Participants |
| Dose 2 Semorinemab Open Label Extension Period | Change From Baseline on the C-SSRS | SI1/SI2 | 0 Participants |
| Dose 2 Semorinemab Open Label Extension Period | Change From Baseline on the C-SSRS | SI4/SI1 | 0 Participants |
| Dose 2 Semorinemab Open Label Extension Period | Change From Baseline on the C-SSRS | No Event/SI1 | 5 Participants |
| Dose 2 Semorinemab Open Label Extension Period | Change From Baseline on the C-SSRS | No Event/ Missing | 1 Participants |
| Dose 2 Semorinemab Open Label Extension Period | Change From Baseline on the C-SSRS | No Event/ SI4 | 0 Participants |
| Dose 2 Semorinemab Open Label Extension Period | Change From Baseline on the C-SSRS | Missing/SI1 | 0 Participants |
| Dose 2 Semorinemab Open Label Extension Period | Change From Baseline on the C-SSRS | SI4/No Event | 0 Participants |
| Dose 2 Semorinemab Open Label Extension Period | Change From Baseline on the C-SSRS | Missing/No Events | 3 Participants |
| Dose 2 Semorinemab Open Label Extension Period | Change From Baseline on the C-SSRS | No Event/No Event | 336 Participants |
| Dose 2 Semorinemab Open Label Extension Period | Change From Baseline on the C-SSRS | Missing/Missing | 0 Participants |
| Dose 2 Semorinemab Open Label Extension Period | Change From Baseline on the C-SSRS | SI4/Missing | 0 Participants |
| Dose 2 Semorinemab Open Label Extension Period | Change From Baseline on the C-SSRS | SI4/SI3 | 1 Participants |
| Dose 2 Semorinemab Open Label Extension Period | Change From Baseline on the C-SSRS | SI2/No Event | 1 Participants |
| Dose 2 Semorinemab Open Label Extension Period | Change From Baseline on the C-SSRS | SI1/SI3 | 0 Participants |
| Dose 2 Semorinemab Open Label Extension Period | Change From Baseline on the C-SSRS | SI1/SI4 | 0 Participants |
| Dose 2 Semorinemab Open Label Extension Period | Change From Baseline on the C-SSRS | SI3/SI3 | 0 Participants |
| Dose 2 Semorinemab Open Label Extension Period | Change From Baseline on the C-SSRS | SI3/Missing | 0 Participants |
| Dose 2 Semorinemab Open Label Extension Period | Change From Baseline on the C-SSRS | SI3/SI1 | 0 Participants |
| Dose 2 Semorinemab Open Label Extension Period | Change From Baseline on the C-SSRS | SI1/Missing | 0 Participants |
| Dose 2 Semorinemab Open Label Extension Period | Change From Baseline on the C-SSRS | SI1/No Event | 8 Participants |
| Dose 2 Semorinemab Open Label Extension Period | Change From Baseline on the C-SSRS | SI4/SI2 | 0 Participants |
| Dose 2 Semorinemab Open Label Extension Period | Change From Baseline on the C-SSRS | SI1/SI1 | 1 Participants |
| Dose 2 Semorinemab Open Label Extension Period | Change From Baseline on the C-SSRS | SI2/SI2 | 0 Participants |
| Dose 2 Semorinemab Open Label Extension Period | Change From Baseline on the C-SSRS | No Event/SI3 | 0 Participants |
| Dose 2 Semorinemab Open Label Extension Period | Change From Baseline on the C-SSRS | SI2/SI4 | 0 Participants |
| Dose 2 Semorinemab Open Label Extension Period | Change From Baseline on the C-SSRS | No Event/ SI2 | 1 Participants |
| Dose 2 Semorinemab Open Label Extension Period | Change From Baseline on the C-SSRS | SI2/Missing | 0 Participants |
Primary
Other Abnormal MRI Findings
Other abnormal MRI findings by visit. For the Double Blind Period, baseline is defined as last results prior to initiation of study drug. For the Open Label Extension Period, baseline is defined as last results prior to entering the open label period.
Time frame: Baseline, Week 9, Week 49, Week 73, Study Treatment Discontinuation, and Week 89
Population: The safety-evaluable population included all participants who were randomly allocated and received at least one dose of study drug (MTAU9937A or placebo) during the double-blind treatment period with treatment groups defined according to actual treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Double Blind Period | Other Abnormal MRI Findings | Cerebrovascular Pathology, Study Treatment Early Discontinuation | 0 Number of participants |
| Placebo Double Blind Period | Other Abnormal MRI Findings | Superficial Hemosiderosis, Baseline | 3 Number of participants |
| Placebo Double Blind Period | Other Abnormal MRI Findings | Territorial Infarct, Study Treatment Early Discontinuation | 0 Number of participants |
| Placebo Double Blind Period | Other Abnormal MRI Findings | Intracranial Tumor, Week 9 | 0 Number of participants |
| Placebo Double Blind Period | Other Abnormal MRI Findings | Superficial Hemosiderosis, Week 9 | 3 Number of participants |
| Placebo Double Blind Period | Other Abnormal MRI Findings | Cerebrovascular Pathology, Baseline | 3 Number of participants |
| Placebo Double Blind Period | Other Abnormal MRI Findings | Lacunar Infarct, Week 73 | 0 Number of participants |
| Placebo Double Blind Period | Other Abnormal MRI Findings | Lacunar Infarct, Week 9 | 0 Number of participants |
| Placebo Double Blind Period | Other Abnormal MRI Findings | Territorial Infarct, Week 49 | 0 Number of participants |
| Placebo Double Blind Period | Other Abnormal MRI Findings | Superficial Hemosiderosis, Week 73 | 0 Number of participants |
| Placebo Double Blind Period | Other Abnormal MRI Findings | CNS Trauma, Week 73 | 0 Number of participants |
| Placebo Double Blind Period | Other Abnormal MRI Findings | Lucunar Infarct, Study Treatment Early Discontinuation | 1 Number of participants |
| Placebo Double Blind Period | Other Abnormal MRI Findings | Territorial Infarct, Week 9 | 0 Number of participants |
| Placebo Double Blind Period | Other Abnormal MRI Findings | Cerebrovascular Pathology, Week 73 | 0 Number of participants |
| Placebo Double Blind Period | Other Abnormal MRI Findings | Intracranial Tumor, Baseline | 0 Number of participants |
| Placebo Double Blind Period | Other Abnormal MRI Findings | Vasogenic Edema/Sulcal Effusion, Week 73 | 1 Number of participants |
| Placebo Double Blind Period | Other Abnormal MRI Findings | Vasogenic Edema/Sulcal Effusion, Week 9 | 0 Number of participants |
| Placebo Double Blind Period | Other Abnormal MRI Findings | Vasogenic Edema/Sulcal Effusion, Week 49 | 0 Number of participants |
| Placebo Double Blind Period | Other Abnormal MRI Findings | Vasogenic Edema/Sulcal Effusion, Baseline | 0 Number of participants |
| Placebo Double Blind Period | Other Abnormal MRI Findings | Intracranial Tumor, Study Treatment Early Discontinuation | 0 Number of participants |
| Placebo Double Blind Period | Other Abnormal MRI Findings | Cerebrovascular Pathology, Week 49 | 0 Number of participants |
| Placebo Double Blind Period | Other Abnormal MRI Findings | Territorial Infarct, Baseline | 3 Number of participants |
| Placebo Double Blind Period | Other Abnormal MRI Findings | Superficial Hemosiderosis, Study Treatment Early Discontinuation | 1 Number of participants |
| Placebo Double Blind Period | Other Abnormal MRI Findings | Cerebrovascular Pathology, Week 9 | 0 Number of participants |
| Placebo Double Blind Period | Other Abnormal MRI Findings | CNS Trauma, Week 49 | 0 Number of participants |
| Placebo Double Blind Period | Other Abnormal MRI Findings | Vasogenic Edema/Sulcal Effusion, Study Treatment Early Discontinuation | 0 Number of participants |
| Placebo Double Blind Period | Other Abnormal MRI Findings | Intracranial Tumor, Week 49 | 0 Number of participants |
| Placebo Double Blind Period | Other Abnormal MRI Findings | Territorial Infarct, Week 73 | 0 Number of participants |
| Placebo Double Blind Period | Other Abnormal MRI Findings | CNS Trauma, Baseline | 0 Number of participants |
| Placebo Double Blind Period | Other Abnormal MRI Findings | CSN Trauma, Study Treatment Early Discontinuation | 0 Number of participants |
| Placebo Double Blind Period | Other Abnormal MRI Findings | Lacunar Infarct, Week 49 | 0 Number of participants |
| Placebo Double Blind Period | Other Abnormal MRI Findings | Intracranial Tumor, Week 73 | 1 Number of participants |
| Placebo Double Blind Period | Other Abnormal MRI Findings | Lacunar Infarct, Baseline | 13 Number of participants |
| Placebo Double Blind Period | Other Abnormal MRI Findings | CNS Trauma, Week 9 | 0 Number of participants |
| Placebo Double Blind Period | Other Abnormal MRI Findings | Superficial Hemosiderosis, Week 49 | 1 Number of participants |
| Dose 1 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Lacunar Infarct, Week 9 | 1 Number of participants |
| Dose 1 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Lacunar Infarct, Baseline | 3 Number of participants |
| Dose 1 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Territorial Infarct, Week 49 | 0 Number of participants |
| Dose 1 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Vasogenic Edema/Sulcal Effusion, Study Treatment Early Discontinuation | 0 Number of participants |
| Dose 1 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Vasogenic Edema/Sulcal Effusion, Week 49 | 0 Number of participants |
| Dose 1 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Territorial Infarct, Week 73 | 0 Number of participants |
| Dose 1 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Cerebrovascular Pathology, Week 73 | 0 Number of participants |
| Dose 1 Semorinemab Double Blind Period | Other Abnormal MRI Findings | CNS Trauma, Week 73 | 0 Number of participants |
| Dose 1 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Intracranial Tumor, Week 73 | 0 Number of participants |
| Dose 1 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Superficial Hemosiderosis, Week 73 | 1 Number of participants |
| Dose 1 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Lacunar Infarct, Week 73 | 1 Number of participants |
| Dose 1 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Superficial Hemosiderosis, Baseline | 0 Number of participants |
| Dose 1 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Superficial Hemosiderosis, Study Treatment Early Discontinuation | 0 Number of participants |
| Dose 1 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Vasogenic Edema/Sulcal Effusion, Baseline | 0 Number of participants |
| Dose 1 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Territorial Infarct, Baseline | 1 Number of participants |
| Dose 1 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Cerebrovascular Pathology, Week 9 | 1 Number of participants |
| Dose 1 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Territorial Infarct, Study Treatment Early Discontinuation | 0 Number of participants |
| Dose 1 Semorinemab Double Blind Period | Other Abnormal MRI Findings | CNS Trauma, Week 9 | 0 Number of participants |
| Dose 1 Semorinemab Double Blind Period | Other Abnormal MRI Findings | CNS Trauma, Baseline | 0 Number of participants |
| Dose 1 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Intracranial Tumor, Week 9 | 0 Number of participants |
| Dose 1 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Lucunar Infarct, Study Treatment Early Discontinuation | 0 Number of participants |
| Dose 1 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Superficial Hemosiderosis, Week 49 | 1 Number of participants |
| Dose 1 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Vasogenic Edema/Sulcal Effusion, Week 73 | 0 Number of participants |
| Dose 1 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Territorial Infarct, Week 9 | 0 Number of participants |
| Dose 1 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Intracranial Tumor, Study Treatment Early Discontinuation | 0 Number of participants |
| Dose 1 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Vasogenic Edema/Sulcal Effusion, Week 9 | 0 Number of participants |
| Dose 1 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Intracranial Tumor, Baseline | 0 Number of participants |
| Dose 1 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Cerebrovascular Pathology, Week 49 | 0 Number of participants |
| Dose 1 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Cerebrovascular Pathology, Baseline | 0 Number of participants |
| Dose 1 Semorinemab Double Blind Period | Other Abnormal MRI Findings | CNS Trauma, Week 49 | 0 Number of participants |
| Dose 1 Semorinemab Double Blind Period | Other Abnormal MRI Findings | CSN Trauma, Study Treatment Early Discontinuation | 0 Number of participants |
| Dose 1 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Intracranial Tumor, Week 49 | 0 Number of participants |
| Dose 1 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Superficial Hemosiderosis, Week 9 | 0 Number of participants |
| Dose 1 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Lacunar Infarct, Week 49 | 0 Number of participants |
| Dose 1 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Cerebrovascular Pathology, Study Treatment Early Discontinuation | 0 Number of participants |
| Dose 2 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Lacunar Infarct, Baseline | 11 Number of participants |
| Dose 2 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Cerebrovascular Pathology, Baseline | 2 Number of participants |
| Dose 2 Semorinemab Double Blind Period | Other Abnormal MRI Findings | CNS Trauma, Baseline | 0 Number of participants |
| Dose 2 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Intracranial Tumor, Baseline | 3 Number of participants |
| Dose 2 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Lacunar Infarct, Week 73 | 0 Number of participants |
| Dose 2 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Superficial Hemosiderosis, Baseline | 2 Number of participants |
| Dose 2 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Vasogenic Edema/Sulcal Effusion, Baseline | 0 Number of participants |
| Dose 2 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Cerebrovascular Pathology, Week 9 | 0 Number of participants |
| Dose 2 Semorinemab Double Blind Period | Other Abnormal MRI Findings | CNS Trauma, Week 9 | 0 Number of participants |
| Dose 2 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Intracranial Tumor, Week 9 | 0 Number of participants |
| Dose 2 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Lacunar Infarct, Week 9 | 0 Number of participants |
| Dose 2 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Superficial Hemosiderosis, Week 9 | 0 Number of participants |
| Dose 2 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Territorial Infarct, Week 9 | 0 Number of participants |
| Dose 2 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Vasogenic Edema/Sulcal Effusion, Week 9 | 1 Number of participants |
| Dose 2 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Cerebrovascular Pathology, Week 49 | 0 Number of participants |
| Dose 2 Semorinemab Double Blind Period | Other Abnormal MRI Findings | CNS Trauma, Week 49 | 0 Number of participants |
| Dose 2 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Intracranial Tumor, Week 49 | 0 Number of participants |
| Dose 2 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Lacunar Infarct, Week 49 | 0 Number of participants |
| Dose 2 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Superficial Hemosiderosis, Week 49 | 1 Number of participants |
| Dose 2 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Territorial Infarct, Week 49 | 0 Number of participants |
| Dose 2 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Vasogenic Edema/Sulcal Effusion, Week 49 | 0 Number of participants |
| Dose 2 Semorinemab Double Blind Period | Other Abnormal MRI Findings | CNS Trauma, Week 73 | 0 Number of participants |
| Dose 2 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Intracranial Tumor, Week 73 | 0 Number of participants |
| Dose 2 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Superficial Hemosiderosis, Week 73 | 0 Number of participants |
| Dose 2 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Territorial Infarct, Week 73 | 0 Number of participants |
| Dose 2 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Vasogenic Edema/Sulcal Effusion, Week 73 | 0 Number of participants |
| Dose 2 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Cerebrovascular Pathology, Study Treatment Early Discontinuation | 0 Number of participants |
| Dose 2 Semorinemab Double Blind Period | Other Abnormal MRI Findings | CSN Trauma, Study Treatment Early Discontinuation | 0 Number of participants |
| Dose 2 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Intracranial Tumor, Study Treatment Early Discontinuation | 0 Number of participants |
| Dose 2 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Lucunar Infarct, Study Treatment Early Discontinuation | 0 Number of participants |
| Dose 2 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Superficial Hemosiderosis, Study Treatment Early Discontinuation | 0 Number of participants |
| Dose 2 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Territorial Infarct, Study Treatment Early Discontinuation | 0 Number of participants |
| Dose 2 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Vasogenic Edema/Sulcal Effusion, Study Treatment Early Discontinuation | 0 Number of participants |
| Dose 2 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Territorial Infarct, Baseline | 0 Number of participants |
| Dose 2 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Cerebrovascular Pathology, Week 73 | 0 Number of participants |
| Dose 3 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Lucunar Infarct, Study Treatment Early Discontinuation | 0 Number of participants |
| Dose 3 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Cerebrovascular Pathology, Study Treatment Early Discontinuation | 0 Number of participants |
| Dose 3 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Intracranial Tumor, Week 49 | 0 Number of participants |
| Dose 3 Semorinemab Double Blind Period | Other Abnormal MRI Findings | CNS Trauma, Week 49 | 0 Number of participants |
| Dose 3 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Superficial Hemosiderosis, Baseline | 0 Number of participants |
| Dose 3 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Lacunar Infarct, Week 9 | 0 Number of participants |
| Dose 3 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Lacunar Infarct, Baseline | 6 Number of participants |
| Dose 3 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Intracranial Tumor, Week 73 | 0 Number of participants |
| Dose 3 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Cerebrovascular Pathology, Week 49 | 0 Number of participants |
| Dose 3 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Superficial Hemosiderosis, Week 73 | 1 Number of participants |
| Dose 3 Semorinemab Double Blind Period | Other Abnormal MRI Findings | CNS Trauma, Week 73 | 0 Number of participants |
| Dose 3 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Vasogenic Edema/Sulcal Effusion, Week 49 | 0 Number of participants |
| Dose 3 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Intracranial Tumor, Baseline | 2 Number of participants |
| Dose 3 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Territorial Infarct, Week 73 | 0 Number of participants |
| Dose 3 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Territorial Infarct, Week 49 | 0 Number of participants |
| Dose 3 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Vasogenic Edema/Sulcal Effusion, Week 73 | 0 Number of participants |
| Dose 3 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Superficial Hemosiderosis, Week 49 | 0 Number of participants |
| Dose 3 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Lacunar Infarct, Week 49 | 0 Number of participants |
| Dose 3 Semorinemab Double Blind Period | Other Abnormal MRI Findings | CSN Trauma, Study Treatment Early Discontinuation | 0 Number of participants |
| Dose 3 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Vasogenic Edema/Sulcal Effusion, Week 9 | 0 Number of participants |
| Dose 3 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Territorial Infarct, Week 9 | 0 Number of participants |
| Dose 3 Semorinemab Double Blind Period | Other Abnormal MRI Findings | CNS Trauma, Baseline | 1 Number of participants |
| Dose 3 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Intracranial Tumor, Study Treatment Early Discontinuation | 0 Number of participants |
| Dose 3 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Superficial Hemosiderosis, Week 9 | 1 Number of participants |
| Dose 3 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Intracranial Tumor, Week 9 | 0 Number of participants |
| Dose 3 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Cerebrovascular Pathology, Week 73 | 0 Number of participants |
| Dose 3 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Superficial Hemosiderosis, Study Treatment Early Discontinuation | 0 Number of participants |
| Dose 3 Semorinemab Double Blind Period | Other Abnormal MRI Findings | CNS Trauma, Week 9 | 0 Number of participants |
| Dose 3 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Cerebrovascular Pathology, Week 9 | 0 Number of participants |
| Dose 3 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Cerebrovascular Pathology, Baseline | 1 Number of participants |
| Dose 3 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Territorial Infarct, Study Treatment Early Discontinuation | 0 Number of participants |
| Dose 3 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Lacunar Infarct, Week 73 | 0 Number of participants |
| Dose 3 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Vasogenic Edema/Sulcal Effusion, Study Treatment Early Discontinuation | 0 Number of participants |
| Dose 3 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Vasogenic Edema/Sulcal Effusion, Baseline | 0 Number of participants |
| Dose 3 Semorinemab Double Blind Period | Other Abnormal MRI Findings | Territorial Infarct, Baseline | 0 Number of participants |
| Dose 2 Semorinemab Open Label Extension Period | Other Abnormal MRI Findings | CNS Trauma, Baseline | 1 Number of participants |
| Dose 2 Semorinemab Open Label Extension Period | Other Abnormal MRI Findings | Territorial Infarct, Baseline | 4 Number of participants |
| Dose 2 Semorinemab Open Label Extension Period | Other Abnormal MRI Findings | Vasogenic Edema/Sulcal Effusion, Baseline | 0 Number of participants |
| Dose 2 Semorinemab Open Label Extension Period | Other Abnormal MRI Findings | Superficial Hemosiderosis, Baseline | 7 Number of participants |
| Dose 2 Semorinemab Open Label Extension Period | Other Abnormal MRI Findings | Intracranial Tumor, Week 89 OLE | 1 Number of participants |
| Dose 2 Semorinemab Open Label Extension Period | Other Abnormal MRI Findings | Cerebrovascular Pathology, Week 89 Open Label Extension (OLE) | 0 Number of participants |
| Dose 2 Semorinemab Open Label Extension Period | Other Abnormal MRI Findings | Lacunar Infarct, Week 89 OLE | 0 Number of participants |
| Dose 2 Semorinemab Open Label Extension Period | Other Abnormal MRI Findings | Superficial Hemosiderosis, Week 89 OLE | 0 Number of participants |
| Dose 2 Semorinemab Open Label Extension Period | Other Abnormal MRI Findings | Territorial Infarct, Week 89 OLE | 0 Number of participants |
| Dose 2 Semorinemab Open Label Extension Period | Other Abnormal MRI Findings | Cerebrovascular Pathology, Baseline | 5 Number of participants |
| Dose 2 Semorinemab Open Label Extension Period | Other Abnormal MRI Findings | Vasogenic Edema/Sulcal Effusion, Week 89 OLE | 1 Number of participants |
| Dose 2 Semorinemab Open Label Extension Period | Other Abnormal MRI Findings | Lacunar Infarct, Baseline | 23 Number of participants |
| Dose 2 Semorinemab Open Label Extension Period | Other Abnormal MRI Findings | CNS Trauma, Week 89 OLE | 0 Number of participants |
| Dose 2 Semorinemab Open Label Extension Period | Other Abnormal MRI Findings | Intracranial Tumor, Baseline | 4 Number of participants |
Primary
Percentage of Participants With Adverse Events
Percentage of participants with at least one adverse event
Time frame: Up to the data cutoff date 15 January 2021 (up to approximately 39 months)
Population: The safety-evaluable population included all participants who were randomly allocated and received at least one dose of study drug (MTAU9937A or placebo) during the double-blind treatment period with treatment groups defined according to actual treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Double Blind Period | Percentage of Participants With Adverse Events | 93.1 Percentage of participants |
| Dose 1 Semorinemab Double Blind Period | Percentage of Participants With Adverse Events | 88.8 Percentage of participants |
| Dose 2 Semorinemab Double Blind Period | Percentage of Participants With Adverse Events | 94.7 Percentage of participants |
| Dose 3 Semorinemab Double Blind Period | Percentage of Participants With Adverse Events | 92.2 Percentage of participants |
| Dose 2 Semorinemab Open Label Extension Period | Percentage of Participants With Adverse Events | 47.5 Percentage of participants |
Secondary
Change From Baseline on the Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog-13) Subscale Score
The ADAS-Cog-13 assesses multiple cognitive domains including memory, comprehension, praxis, orientation, and spontaneous speech. Most of these are assessed by tests although some are rated by the clinician on a 5-point scale. The ADAS-Cog-13 is the ADAS-Cog-11 with 2 further items: delayed word recall and total digit cancellation. The score range for ADAS-Cog-13 is from 0 to 85 with high scores representing severe dysfunction. The difference in mean change from Baseline to Week 73 between Semorinemab doses and Placebo treated participants was estimated.
Time frame: Baseline and 73 weeks
Population: Modified intent-to-treat (mITT) population included all randomized participants who received at least one dose of study drug and had at least one postbaseline primary efficacy Clinical Dementia Rating-Sum of Boxes (CDR-SB) measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Double Blind Period | Change From Baseline on the Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog-13) Subscale Score | 6.56 Score on a scale | Standard Error 0.777 |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog-13) Subscale Score | 8.68 Score on a scale | Standard Error 0.937 |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog-13) Subscale Score | 6 Score on a scale | Standard Error 0.769 |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog-13) Subscale Score | 7.58 Score on a scale | Standard Error 0.932 |
p-value: 0.0783Mixed-effect Model Repeated Measures
p-value: 0.601Mixed-effect Model Repeated Measures
p-value: 0.3961Mixed-effect Model Repeated Measures
Secondary
Change From Baseline on the Alzheimer's Disease Cooperative Study Group-Activities of Daily Living Inventory
The ADCS-ADL (Alzheimer's Disease Cooperative Study-Activities of Daily Living) is the scale most widely used to assess functional outcomes in participants with AD. The ADCS-ADL covers both basic ADL (e.g., eating and toileting) and more complex 'instrumental' ADL or iADL (e.g., using the telephone, managing finances and preparing a meal). The ADCS-ADL consists of 23 questions with a score range of 0 to 78 where a higher score represents better function. The difference in mean change from Baseline to Week 73 between Semorinemab doses and Placebo treated participants was estimated.
Time frame: Baseline and 73 weeks
Population: Modified intent-to-treat (mITT) population included all randomized participants who received at least one dose of study drug and had at least one postbaseline primary efficacy Clinical Dementia Rating-Sum of Boxes (CDR-SB) measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Double Blind Period | Change From Baseline on the Alzheimer's Disease Cooperative Study Group-Activities of Daily Living Inventory | -8.55 Score on a scale | Standard Error 0.996 |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the Alzheimer's Disease Cooperative Study Group-Activities of Daily Living Inventory | -9.52 Score on a scale | Standard Error 1.179 |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the Alzheimer's Disease Cooperative Study Group-Activities of Daily Living Inventory | -7.75 Score on a scale | Standard Error 0.986 |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the Alzheimer's Disease Cooperative Study Group-Activities of Daily Living Inventory | -7.99 Score on a scale | Standard Error 1.183 |
p-value: 0.5235Mixed-effect Model Repeated Measures
p-value: 0.5612Mixed-effect Model Repeated Measures
p-value: 0.713Mixed-effect Model Repeated Measures
Secondary
Change From Baseline on the Amsterdam Instrumental Activity of Daily Living (iADL) Questionnaire
The Amsterdam iADL questionnaire is an informant-based instrument for measuring iADL problems in participants with dementia. This instrument consists of 70 items, scored on a 5-point scale, that uses item response theory for scoring. Items presented to the informant are tailored to responses to earlier items; thus each administration of the Amsterdam iADL may consist of less than the total of 70 items. The resulting score ranges from 20 to 80 with lower scores indicating poorer performance. A decrease in the outcome measure from baseline corresponds to disease worsening. The difference in mean change from Baseline to Week 73 between Semorinemab doses and Placebo treated participants was estimated.
Time frame: Baseline and 73 weeks
Population: Modified intent-to-treat (mITT) population included all randomized participants who received at least one dose of study drug and had at least one postbaseline primary efficacy Clinical Dementia Rating-Sum of Boxes (CDR-SB) measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Double Blind Period | Change From Baseline on the Amsterdam Instrumental Activity of Daily Living (iADL) Questionnaire | -6.59 Score on a scale | Standard Error 0.856 |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the Amsterdam Instrumental Activity of Daily Living (iADL) Questionnaire | -6.55 Score on a scale | Standard Error 0.999 |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the Amsterdam Instrumental Activity of Daily Living (iADL) Questionnaire | -6.92 Score on a scale | Standard Error 0.824 |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the Amsterdam Instrumental Activity of Daily Living (iADL) Questionnaire | -7.31 Score on a scale | Standard Error 1.013 |
p-value: 0.9749Mixed-effect Model Repeated Measures
p-value: 0.7718Mixed-effect Model Repeated Measures
p-value: 0.5789Mixed-effect Model Repeated Measures
Secondary
Change From Baseline on the Repeatable Battery for Assessment of Neuropsychological Status (RBANS)
The RBANS is a validated neuropsychological assessment has been shown to be a useful tool in both clinical and research settings. The RBANS consists of ten subtests that are combined to provide five indices, one for each of the five domains tested (immediate memory, visuospatial/constructional, language, attention, and delayed memory). Scores range from 40 to 160 and a higher score indicates better cognitive functioning. A decrease in the outcome measure from baseline corresponds to disease worsening. The difference in mean change from Baseline to Week 73 between Semorinemab doses and Placebo treated participants was estimated.
Time frame: Baseline and 73 weeks
Population: Modified intent-to-treat (mITT) population included all randomized participants who received at least one dose of study drug and had at least one postbaseline primary efficacy Clinical Dementia Rating-Sum of Boxes (CDR-SB) measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Double Blind Period | Change From Baseline on the Repeatable Battery for Assessment of Neuropsychological Status (RBANS) | -5.53 Score on a scale | Standard Error 0.787 |
| Dose 1 Semorinemab Double Blind Period | Change From Baseline on the Repeatable Battery for Assessment of Neuropsychological Status (RBANS) | -5.25 Score on a scale | Standard Error 0.93 |
| Dose 2 Semorinemab Double Blind Period | Change From Baseline on the Repeatable Battery for Assessment of Neuropsychological Status (RBANS) | -4.62 Score on a scale | Standard Error 0.765 |
| Dose 3 Semorinemab Double Blind Period | Change From Baseline on the Repeatable Battery for Assessment of Neuropsychological Status (RBANS) | -6.15 Score on a scale | Standard Error 0.926 |
p-value: 0.8198Mixed-effect Model Repeated Measures
p-value: 0.3961Mixed-effect Model Repeated Measures
p-value: 0.6043Mixed-effect Model Repeated Measures
Secondary
Presence of Anti-drug Antibodies During the Study Relative to Their Presence at Baseline
Presence of anti-drug antibodies during the study relative to their presence at baseline.
Time frame: Up to 109 weeks
Population: The immunogenicity analyses will include participants with at least one predose and one postdose ADA assessment, with participants grouped according to treatment arm.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Double Blind Period | Presence of Anti-drug Antibodies During the Study Relative to Their Presence at Baseline | Baseline | 0 Percentage of participants |
| Dose 1 Semorinemab Double Blind Period | Presence of Anti-drug Antibodies During the Study Relative to Their Presence at Baseline | Baseline | 0 Percentage of participants |
| Dose 1 Semorinemab Double Blind Period | Presence of Anti-drug Antibodies During the Study Relative to Their Presence at Baseline | Post-baseline | 0 Percentage of participants |
| Dose 2 Semorinemab Double Blind Period | Presence of Anti-drug Antibodies During the Study Relative to Their Presence at Baseline | Post-baseline | 0 Percentage of participants |
| Dose 2 Semorinemab Double Blind Period | Presence of Anti-drug Antibodies During the Study Relative to Their Presence at Baseline | Baseline | 0 Percentage of participants |
| Dose 3 Semorinemab Double Blind Period | Presence of Anti-drug Antibodies During the Study Relative to Their Presence at Baseline | Baseline | 0 Percentage of participants |
| Dose 3 Semorinemab Double Blind Period | Presence of Anti-drug Antibodies During the Study Relative to Their Presence at Baseline | Post-baseline | 0 Percentage of participants |
Secondary
Serum Concentrations of Semorinemab at Specified Timepoints
Serum concentrations of Semorinemab at specified timepoints.
Time frame: Up to 109 weeks
Population: The PK-evaluable population is defined as patients who received Semorinemab treatment and had at least one measureable PK concentration.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 9, 30 Minutes Postdose | 889 ug/mL | Standard Deviation 321 |
| Placebo Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 1, 1 Hour Postdose | 472 ug/mL | Standard Deviation 131 |
| Placebo Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 65, 0-4 Hours Predose | 405 ug/mL | Standard Deviation 127 |
| Placebo Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 13, 0-4 Hours Predose | 360 ug/mL | Standard Deviation 105 |
| Placebo Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 77 OLE, 2 hours Postdose | 1830 ug/mL | Standard Deviation 552 |
| Placebo Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 49, 30 Minutes Postdose | 871 ug/mL | Standard Deviation 260 |
| Placebo Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 13, 30 Minutes Postdose | 998 ug/mL | Standard Deviation 896 |
| Placebo Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 3, 0-4 hours Predose | 184 ug/mL | Standard Deviation 52.7 |
| Placebo Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 49, 0-4 Hours Predose | 377 ug/mL | Standard Deviation 105 |
| Placebo Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 33, 30 Minutes Postdose | 801 ug/mL | Standard Deviation 260 |
| Placebo Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 17, 0-4 Hours Predose | 386 ug/mL | Standard Deviation 116 |
| Placebo Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 93 OLE, 30 Minutes Postdose | 1920 ug/mL | Standard Deviation 431 |
| Placebo Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 33, 0-4 Hours Predose | 404 ug/mL | Standard Deviation 134 |
| Placebo Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 17, 30 Minutes Postdose | 819 ug/mL | Standard Deviation 242 |
| Placebo Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 77 OLE, 1 hour Postdose | 1700 ug/mL | Standard Deviation 523 |
| Placebo Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 3, 30 min Post dose | 718 ug/mL | Standard Deviation 198 |
| Placebo Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 93 OLE, 0-4 Hours Pre-dose | 632 ug/mL | Standard Deviation 37.5 |
| Placebo Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 77 OLE, 0-4 Hours Predose | 180 ug/mL | Standard Deviation 71 |
| Placebo Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 5, 0-4 Hours Predose | 318 ug/mL | Standard Deviation 81.5 |
| Placebo Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 1, 2 Hours Postdose | 476 ug/mL | Standard Deviation 123 |
| Placebo Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 1, 0-4 Hours Predose | NA ug/mL | — |
| Placebo Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 5, 30 min Postdose | 908 ug/mL | Standard Deviation 508 |
| Placebo Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 77 OLE, 4 hours Postdose | 1850 ug/mL | Standard Deviation 516 |
| Placebo Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 73 | 327 ug/mL | Standard Deviation 154 |
| Placebo Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 9, 0-4 hours Predose | 344 ug/mL | Standard Deviation 128 |
| Placebo Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 1, 4 Hours postdose | 463 ug/mL | Standard Deviation 135 |
| Placebo Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 65, 30 Minutes Postdose | 963 ug/mL | Standard Deviation 401 |
| Dose 1 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 73, 1 Hour Postdose | 1910 ug/mL | — |
| Dose 1 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 1, 2 Hours Postdose | 1510 ug/mL | Standard Deviation 419 |
| Dose 1 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 1, 0-4 Hours Predose | NA ug/mL | — |
| Dose 1 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 1, 1 Hour Postdose | 1580 ug/mL | Standard Deviation 496 |
| Dose 1 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 1, 4 Hours postdose | 1370 ug/mL | Standard Deviation 405 |
| Dose 1 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 3, 0-4 hours Predose | 601 ug/mL | Standard Deviation 211 |
| Dose 1 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 3, 30 min Post dose | 2320 ug/mL | Standard Deviation 581 |
| Dose 1 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 5, 0-4 Hours Predose | 955 ug/mL | Standard Deviation 256 |
| Dose 1 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 5, 30 min Postdose | 2780 ug/mL | Standard Deviation 695 |
| Dose 1 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 9, 0-4 hours Predose | 961 ug/mL | Standard Deviation 288 |
| Dose 1 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 9, 30 Minutes Postdose | 2790 ug/mL | Standard Deviation 757 |
| Dose 1 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 13, 0-4 Hours Predose | 1060 ug/mL | Standard Deviation 333 |
| Dose 1 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 13, 30 Minutes Postdose | 2900 ug/mL | Standard Deviation 668 |
| Dose 1 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 17, 0-4 Hours Predose | 1040 ug/mL | Standard Deviation 316 |
| Dose 1 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 17, 30 Minutes Postdose | 2930 ug/mL | Standard Deviation 902 |
| Dose 1 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 33, 0-4 Hours Predose | 960 ug/mL | Standard Deviation 277 |
| Dose 1 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 33, 30 Minutes Postdose | 2540 ug/mL | Standard Deviation 853 |
| Dose 1 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 49, 0-4 Hours Predose | 1060 ug/mL | Standard Deviation 332 |
| Dose 1 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 49, 30 Minutes Postdose | 2810 ug/mL | Standard Deviation 967 |
| Dose 1 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 65, 0-4 Hours Predose | 1170 ug/mL | Standard Deviation 276 |
| Dose 1 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 65, 30 Minutes Postdose | 2930 ug/mL | Standard Deviation 830 |
| Dose 1 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 73 | 1030 ug/mL | Standard Deviation 451 |
| Dose 1 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 73, 0-4 Hours Predose | 382 ug/mL | — |
| Dose 1 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 73, 2 Hours Postdose | 1740 ug/mL | — |
| Dose 1 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 73, 4 Hours Postdose | 1710 ug/mL | — |
| Dose 1 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 77 OLE, 0-4 Hours Predose | 724 ug/mL | Standard Deviation 167 |
| Dose 1 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 77 OLE, 1 hour Postdose | 2460 ug/mL | Standard Deviation 868 |
| Dose 1 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 77 OLE, 2 hours Postdose | 2270 ug/mL | Standard Deviation 442 |
| Dose 1 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 77 OLE, 4 hours Postdose | 2270 ug/mL | Standard Deviation 480 |
| Dose 1 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 93 OLE, 0-4 Hours Pre-dose | 1040 ug/mL | Standard Deviation 113 |
| Dose 1 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 93 OLE, 30 Minutes Postdose | 2570 ug/mL | Standard Deviation 91.9 |
| Dose 1 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 109 OLE, 0-4 Hours Predose | 1270 ug/mL | — |
| Dose 1 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 109 OLE, 30 Minutes Postdose | 3330 ug/mL | — |
| Dose 2 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 93 OLE, 0-4 Hours Pre-dose | 1290 ug/mL | Standard Deviation 307 |
| Dose 2 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 65, 30 Minutes Postdose | 4710 ug/mL | Standard Deviation 1450 |
| Dose 2 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 5, 30 min Postdose | 4860 ug/mL | Standard Deviation 1250 |
| Dose 2 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 77 OLE, 2 hours Postdose | 2510 ug/mL | Standard Deviation 579 |
| Dose 2 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 73 | 1830 ug/mL | Standard Deviation 752 |
| Dose 2 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 1, 2 Hours Postdose | 2600 ug/mL | Standard Deviation 707 |
| Dose 2 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 5, 0-4 Hours Predose | 1920 ug/mL | Standard Deviation 614 |
| Dose 2 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 1, 0-4 Hours Predose | NA ug/mL | — |
| Dose 2 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 77 OLE, 4 hours Postdose | 2790 ug/mL | Standard Deviation 558 |
| Dose 2 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 3, 30 min Post dose | 4190 ug/mL | Standard Deviation 1010 |
| Dose 2 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 1, 1 Hour Postdose | 2690 ug/mL | Standard Deviation 689 |
| Dose 2 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 17, 30 Minutes Postdose | 4770 ug/mL | Standard Deviation 1270 |
| Dose 2 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 17, 0-4 Hours Predose | 1890 ug/mL | Standard Deviation 522 |
| Dose 2 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 77 OLE, 0-4 Hours Predose | 1030 ug/mL | Standard Deviation 345 |
| Dose 2 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 33, 0-4 Hours Predose | 2050 ug/mL | Standard Deviation 648 |
| Dose 2 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 17 | 1750 ug/mL | — |
| Dose 2 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 3, 0-4 hours Predose | 1100 ug/mL | Standard Deviation 449 |
| Dose 2 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 33, 30 Minutes Postdose | 4800 ug/mL | Standard Deviation 1200 |
| Dose 2 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 13, 30 Minutes Postdose | 4880 ug/mL | Standard Deviation 1250 |
| Dose 2 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 93 OLE, 30 Minutes Postdose | 2880 ug/mL | Standard Deviation 492 |
| Dose 2 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 49, 0-4 Hours Predose | 2160 ug/mL | Standard Deviation 605 |
| Dose 2 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 13, 0-4 Hours Predose | 1910 ug/mL | Standard Deviation 545 |
| Dose 2 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 77 OLE, 1 hour Postdose | 2670 ug/mL | Standard Deviation 707 |
| Dose 2 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 49, 30 Minutes Postdose | 4960 ug/mL | Standard Deviation 1030 |
| Dose 2 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 65 | 2100 ug/mL | — |
| Dose 2 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 9, 30 Minutes Postdose | 4960 ug/mL | Standard Deviation 1270 |
| Dose 2 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 1, 4 Hours postdose | 2570 ug/mL | Standard Deviation 785 |
| Dose 2 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 65, 0-4 Hours Predose | 2020 ug/mL | Standard Deviation 681 |
| Dose 2 Semorinemab Double Blind Period | Serum Concentrations of Semorinemab at Specified Timepoints | Week 9, 0-4 hours Predose | 1840 ug/mL | Standard Deviation 513 |