← Trials/Trial dossier/NCT03289143
TerminatedPhase 2Results posted
A Study to Evaluate the Efficacy and Safety of Semorinemab in Patients With Prodromal to Mild Alzheimer's Disease
A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study of MTAU9937A in Patients With Prodromal to Mild Alzheimer's Disease
Lead sponsor
Asset
Semorinemab
Listed sites
133
Recruiting sites
-
Enrollment
457
actual
Study population
Alzheimer’s disease
Key I/E criteria
•prodromal AD•Amyloid biomarker required (PET/CSF)•MMSE ≥20•MRI contraindications excluded
Primary endpoints
•Clinical Dementia Rating-Sum of Boxes (CDR-SB)•Adverse Events•Change From Baseline on the C-SSRS
Footprint
Where this trial recruits
Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.
Identifiers
Registered as
Eudract number2017-001800-31
Org study IDGN39763
NCT IDNCT03289143
Timeline
Milestones
Study first posted2017-09-20actual
Study start2017-10-04actual
Primary completion2021-01-15actual
Study completion2021-01-15actual
Last update posted2022-03-16actual
Results first posted2022-03-16actual
Assets
Drug assets
Study populations
Who this study enrolls
Alzheimer’s disease
Eligibility
Who can enroll
Minimum age50 Years
Maximum age80 Years
SexAll
Healthy volunteersNot accepted
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
Endpoints (20)
What's being measured
Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.
Coverage by outcome category
Other (unclassified)
8
Global cognition
6
Function / daily living
2
Neuroimaging
2
Safety / tolerability / PK
2
Global cognition
6 endpointsPrimary/protocol endpoint
Change From Baseline on the CDR-SB
Time frame:Baseline and 73 Weeks
Clinical Dementia Rating-Sum of Boxes (CDR-SB)
change from baseline, improvement
Primary/registry result
Change From Baseline on the CDR-SB
Time frame:Baseline and 73 Weeks
Clinical Dementia Rating-Sum of Boxes (CDR-SB)
change from baseline, improvement
Posted result
| Group | Value (mean), Units on a scale | Standard error |
|---|---|---|
| Placebo Double Blind Periodn=105 Participants | 2.19 | 0.226 |
| Dose 1 Semorinemab Double Blind Periodn=77 Participants | 2.36 | 0.268 |
| Dose 2 Semorinemab Double Blind Periodn=113 Participants | 2.36 | 0.222 |
| Dose 3 Semorinemab Double Blind Periodn=74 Participants | 2.41 | 0.27 |
p0.6147Mixed-effect Model Repeated Measures
p0.5778Mixed-effect Model Repeated Measures
p0.5136Mixed-effect Model Repeated Measures
Secondary/protocol endpoint
Change From Baseline on the Repeatable Battery for Assessment of Neuropsychological Status (RBANS)
Time frame:Baseline and 73 weeks
change from baseline, improvement
Secondary/protocol endpoint
Change From Baseline on the Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog-13) Subscale Score
Time frame:Baseline and 73 weeks
ADAS-Cog
change from baseline, improvement
Secondary/registry result
Change From Baseline on the Repeatable Battery for Assessment of Neuropsychological Status (RBANS)
Time frame:Baseline and 73 weeks
change from baseline, improvement
Posted result
| Group | Value (mean), Score on a scale | Standard error |
|---|---|---|
| Placebo Double Blind Periodn=87 Participants | -5.53 | 0.787 |
| Dose 1 Semorinemab Double Blind Periodn=62 Participants | -5.25 | 0.93 |
| Dose 2 Semorinemab Double Blind Periodn=93 Participants | -4.62 | 0.765 |
| Dose 3 Semorinemab Double Blind Periodn=63 Participants | -6.15 | 0.926 |
p0.8198Mixed-effect Model Repeated Measures
p0.3961Mixed-effect Model Repeated Measures
p0.6043Mixed-effect Model Repeated Measures
Secondary/registry result
Change From Baseline on the Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog-13) Subscale Score
Time frame:Baseline and 73 weeks
ADAS-Cog
change from baseline, improvement
Posted result
| Group | Value (mean), Score on a scale | Standard error |
|---|---|---|
| Placebo Double Blind Periodn=94 Participants | 6.56 | 0.777 |
| Dose 1 Semorinemab Double Blind Periodn=67 Participants | 8.68 | 0.937 |
| Dose 2 Semorinemab Double Blind Periodn=97 Participants | 6 | 0.769 |
| Dose 3 Semorinemab Double Blind Periodn=66 Participants | 7.58 | 0.932 |
p0.0783Mixed-effect Model Repeated Measures
p0.6010Mixed-effect Model Repeated Measures
p0.3961Mixed-effect Model Repeated Measures
Function / daily living
2 endpointsSecondary/protocol endpoint
Change From Baseline on the Alzheimer's Disease Cooperative Study Group-Activities of Daily Living Inventory
Time frame:Baseline and 73 weeks
ADCS-Activities of Daily Living (ADCS-ADL)
change from baseline, improvement
Secondary/registry result
Change From Baseline on the Alzheimer's Disease Cooperative Study Group-Activities of Daily Living Inventory
Time frame:Baseline and 73 weeks
ADCS-Activities of Daily Living (ADCS-ADL)
change from baseline, improvement
Posted result
| Group | Value (mean), Score on a scale | Standard error |
|---|---|---|
| Placebo Double Blind Periodn=104 Participants | -8.55 | 0.996 |
| Dose 1 Semorinemab Double Blind Periodn=76 Participants | -9.52 | 1.179 |
| Dose 2 Semorinemab Double Blind Periodn=112 Participants | -7.75 | 0.986 |
| Dose 3 Semorinemab Double Blind Periodn=74 Participants | -7.99 | 1.183 |
p0.5235Mixed-effect Model Repeated Measures
p0.5612Mixed-effect Model Repeated Measures
p0.7130Mixed-effect Model Repeated Measures
Neuroimaging
2 endpointsPrimary/protocol endpoint
Other Abnormal MRI Findings
Time frame:Baseline, Week 9, Week 49, Week 73, Study Treatment Discontinuation, and Week 89
descriptive
Primary/registry result
Other Abnormal MRI Findings
Time frame:Baseline, Week 9, Week 49, Week 73, Study Treatment Discontinuation, and Week 89
descriptive
Posted result
| Group | Value (number), Number of participants | Reported bounds |
|---|---|---|
| Placebo Double Blind PeriodCerebrovascular Pathology, Baselinen=135 Participants | 3 | - |
| CNS Trauma, Baselinen=135 Participants | 0 | - |
| Intracranial Tumor, Baselinen=135 Participants | 0 | - |
| Lacunar Infarct, Baselinen=135 Participants | 13 | - |
| Superficial Hemosiderosis, Baselinen=135 Participants | 3 | - |
| Territorial Infarct, Baselinen=135 Participants | 3 | - |
| Vasogenic Edema/Sulcal Effusion, Baselinen=135 Participants | 0 | - |
| Cerebrovascular Pathology, Week 9n=135 Participants | 0 | - |
| CNS Trauma, Week 9n=135 Participants | 0 | - |
| Intracranial Tumor, Week 9n=135 Participants | 0 | - |
| Lacunar Infarct, Week 9n=135 Participants | 0 | - |
| Superficial Hemosiderosis, Week 9n=135 Participants | 3 | - |
| Territorial Infarct, Week 9n=135 Participants | 0 | - |
| Vasogenic Edema/Sulcal Effusion, Week 9n=135 Participants | 0 | - |
| Cerebrovascular Pathology, Week 49n=135 Participants | 0 | - |
| CNS Trauma, Week 49n=135 Participants | 0 | - |
| Intracranial Tumor, Week 49n=135 Participants | 0 | - |
| Lacunar Infarct, Week 49n=135 Participants | 0 | - |
| Superficial Hemosiderosis, Week 49n=135 Participants | 1 | - |
| Territorial Infarct, Week 49n=135 Participants | 0 | - |
| Vasogenic Edema/Sulcal Effusion, Week 49n=135 Participants | 0 | - |
| Cerebrovascular Pathology, Week 73n=135 Participants | 0 | - |
| CNS Trauma, Week 73n=135 Participants | 0 | - |
| Intracranial Tumor, Week 73n=135 Participants | 1 | - |
| Lacunar Infarct, Week 73n=135 Participants | 0 | - |
| Superficial Hemosiderosis, Week 73n=135 Participants | 0 | - |
| Territorial Infarct, Week 73n=135 Participants | 0 | - |
| Vasogenic Edema/Sulcal Effusion, Week 73n=135 Participants | 1 | - |
| Cerebrovascular Pathology, Study Treatment Early Discontinuationn=135 Participants | 0 | - |
| CSN Trauma, Study Treatment Early Discontinuationn=135 Participants | 0 | - |
| Intracranial Tumor, Study Treatment Early Discontinuationn=135 Participants | 0 | - |
| Lucunar Infarct, Study Treatment Early Discontinuationn=135 Participants | 1 | - |
| Superficial Hemosiderosis, Study Treatment Early Discontinuationn=135 Participants | 1 | - |
| Territorial Infarct, Study Treatment Early Discontinuationn=135 Participants | 0 | - |
| Vasogenic Edema/Sulcal Effusion, Study Treatment Early Discontinuationn=135 Participants | 0 | - |
| Dose 1 Semorinemab Double Blind PeriodCerebrovascular Pathology, Baselinen=94 Participants | 0 | - |
| CNS Trauma, Baselinen=94 Participants | 0 | - |
| Intracranial Tumor, Baselinen=94 Participants | 0 | - |
| Lacunar Infarct, Baselinen=94 Participants | 3 | - |
| Superficial Hemosiderosis, Baselinen=94 Participants | 0 | - |
| Territorial Infarct, Baselinen=94 Participants | 1 | - |
| Vasogenic Edema/Sulcal Effusion, Baselinen=94 Participants | 0 | - |
| Cerebrovascular Pathology, Week 9n=94 Participants | 1 | - |
| CNS Trauma, Week 9n=94 Participants | 0 | - |
| Intracranial Tumor, Week 9n=94 Participants | 0 | - |
| Lacunar Infarct, Week 9n=94 Participants | 1 | - |
| Superficial Hemosiderosis, Week 9n=94 Participants | 0 | - |
| Territorial Infarct, Week 9n=94 Participants | 0 | - |
| Vasogenic Edema/Sulcal Effusion, Week 9n=94 Participants | 0 | - |
| Cerebrovascular Pathology, Week 49n=94 Participants | 0 | - |
| CNS Trauma, Week 49n=94 Participants | 0 | - |
| Intracranial Tumor, Week 49n=94 Participants | 0 | - |
| Lacunar Infarct, Week 49n=94 Participants | 0 | - |
| Superficial Hemosiderosis, Week 49n=94 Participants | 1 | - |
| Territorial Infarct, Week 49n=94 Participants | 0 | - |
| Vasogenic Edema/Sulcal Effusion, Week 49n=94 Participants | 0 | - |
| Cerebrovascular Pathology, Week 73n=94 Participants | 0 | - |
| CNS Trauma, Week 73n=94 Participants | 0 | - |
| Intracranial Tumor, Week 73n=94 Participants | 0 | - |
| Lacunar Infarct, Week 73n=94 Participants | 1 | - |
| Superficial Hemosiderosis, Week 73n=94 Participants | 1 | - |
| Territorial Infarct, Week 73n=94 Participants | 0 | - |
| Vasogenic Edema/Sulcal Effusion, Week 73n=94 Participants | 0 | - |
| Cerebrovascular Pathology, Study Treatment Early Discontinuationn=94 Participants | 0 | - |
| CSN Trauma, Study Treatment Early Discontinuationn=94 Participants | 0 | - |
| Intracranial Tumor, Study Treatment Early Discontinuationn=94 Participants | 0 | - |
| Lucunar Infarct, Study Treatment Early Discontinuationn=94 Participants | 0 | - |
| Superficial Hemosiderosis, Study Treatment Early Discontinuationn=94 Participants | 0 | - |
| Territorial Infarct, Study Treatment Early Discontinuationn=94 Participants | 0 | - |
| Vasogenic Edema/Sulcal Effusion, Study Treatment Early Discontinuationn=94 Participants | 0 | - |
| Dose 2 Semorinemab Double Blind PeriodCerebrovascular Pathology, Baselinen=136 Participants | 2 | - |
| CNS Trauma, Baselinen=136 Participants | 0 | - |
| Intracranial Tumor, Baselinen=136 Participants | 3 | - |
| Lacunar Infarct, Baselinen=136 Participants | 11 | - |
| Superficial Hemosiderosis, Baselinen=136 Participants | 2 | - |
| Territorial Infarct, Baselinen=136 Participants | 0 | - |
| Vasogenic Edema/Sulcal Effusion, Baselinen=136 Participants | 0 | - |
| Cerebrovascular Pathology, Week 9n=136 Participants | 0 | - |
| CNS Trauma, Week 9n=136 Participants | 0 | - |
| Intracranial Tumor, Week 9n=136 Participants | 0 | - |
| Lacunar Infarct, Week 9n=136 Participants | 0 | - |
| Superficial Hemosiderosis, Week 9n=136 Participants | 0 | - |
| Territorial Infarct, Week 9n=136 Participants | 0 | - |
| Vasogenic Edema/Sulcal Effusion, Week 9n=136 Participants | 1 | - |
| Cerebrovascular Pathology, Week 49n=136 Participants | 0 | - |
| CNS Trauma, Week 49n=136 Participants | 0 | - |
| Intracranial Tumor, Week 49n=136 Participants | 0 | - |
| Lacunar Infarct, Week 49n=136 Participants | 0 | - |
| Superficial Hemosiderosis, Week 49n=136 Participants | 1 | - |
| Territorial Infarct, Week 49n=136 Participants | 0 | - |
| Vasogenic Edema/Sulcal Effusion, Week 49n=136 Participants | 0 | - |
| Cerebrovascular Pathology, Week 73n=136 Participants | 0 | - |
| CNS Trauma, Week 73n=136 Participants | 0 | - |
| Intracranial Tumor, Week 73n=136 Participants | 0 | - |
| Lacunar Infarct, Week 73n=136 Participants | 0 | - |
| Superficial Hemosiderosis, Week 73n=136 Participants | 0 | - |
| Territorial Infarct, Week 73n=136 Participants | 0 | - |
| Vasogenic Edema/Sulcal Effusion, Week 73n=136 Participants | 0 | - |
| Cerebrovascular Pathology, Study Treatment Early Discontinuationn=136 Participants | 0 | - |
| CSN Trauma, Study Treatment Early Discontinuationn=136 Participants | 0 | - |
| Intracranial Tumor, Study Treatment Early Discontinuationn=136 Participants | 0 | - |
| Lucunar Infarct, Study Treatment Early Discontinuationn=136 Participants | 0 | - |
| Superficial Hemosiderosis, Study Treatment Early Discontinuationn=136 Participants | 0 | - |
| Territorial Infarct, Study Treatment Early Discontinuationn=136 Participants | 0 | - |
| Vasogenic Edema/Sulcal Effusion, Study Treatment Early Discontinuationn=136 Participants | 0 | - |
| Dose 3 Semorinemab Double Blind PeriodCerebrovascular Pathology, Baselinen=92 Participants | 1 | - |
| CNS Trauma, Baselinen=92 Participants | 1 | - |
| Intracranial Tumor, Baselinen=92 Participants | 2 | - |
| Lacunar Infarct, Baselinen=92 Participants | 6 | - |
| Superficial Hemosiderosis, Baselinen=92 Participants | 0 | - |
| Territorial Infarct, Baselinen=92 Participants | 0 | - |
| Vasogenic Edema/Sulcal Effusion, Baselinen=92 Participants | 0 | - |
| Cerebrovascular Pathology, Week 9n=92 Participants | 0 | - |
| CNS Trauma, Week 9n=92 Participants | 0 | - |
| Intracranial Tumor, Week 9n=92 Participants | 0 | - |
| Lacunar Infarct, Week 9n=92 Participants | 0 | - |
| Superficial Hemosiderosis, Week 9n=92 Participants | 1 | - |
| Territorial Infarct, Week 9n=92 Participants | 0 | - |
| Vasogenic Edema/Sulcal Effusion, Week 9n=92 Participants | 0 | - |
| Cerebrovascular Pathology, Week 49n=92 Participants | 0 | - |
| CNS Trauma, Week 49n=92 Participants | 0 | - |
| Intracranial Tumor, Week 49n=92 Participants | 0 | - |
| Lacunar Infarct, Week 49n=92 Participants | 0 | - |
| Superficial Hemosiderosis, Week 49n=92 Participants | 0 | - |
| Territorial Infarct, Week 49n=92 Participants | 0 | - |
| Vasogenic Edema/Sulcal Effusion, Week 49n=92 Participants | 0 | - |
| Cerebrovascular Pathology, Week 73n=92 Participants | 0 | - |
| CNS Trauma, Week 73n=92 Participants | 0 | - |
| Intracranial Tumor, Week 73n=92 Participants | 0 | - |
| Lacunar Infarct, Week 73n=92 Participants | 0 | - |
| Superficial Hemosiderosis, Week 73n=92 Participants | 1 | - |
| Territorial Infarct, Week 73n=92 Participants | 0 | - |
| Vasogenic Edema/Sulcal Effusion, Week 73n=92 Participants | 0 | - |
| Cerebrovascular Pathology, Study Treatment Early Discontinuationn=92 Participants | 0 | - |
| CSN Trauma, Study Treatment Early Discontinuationn=92 Participants | 0 | - |
| Intracranial Tumor, Study Treatment Early Discontinuationn=92 Participants | 0 | - |
| Lucunar Infarct, Study Treatment Early Discontinuationn=92 Participants | 0 | - |
| Superficial Hemosiderosis, Study Treatment Early Discontinuationn=92 Participants | 0 | - |
| Territorial Infarct, Study Treatment Early Discontinuationn=92 Participants | 0 | - |
| Vasogenic Edema/Sulcal Effusion, Study Treatment Early Discontinuationn=92 Participants | 0 | - |
| Dose 2 Semorinemab Open Label Extension PeriodCerebrovascular Pathology, Baselinen=360 Participants | 5 | - |
| CNS Trauma, Baselinen=360 Participants | 1 | - |
| Intracranial Tumor, Baselinen=360 Participants | 4 | - |
| Lacunar Infarct, Baselinen=360 Participants | 23 | - |
| Superficial Hemosiderosis, Baselinen=360 Participants | 7 | - |
| Territorial Infarct, Baselinen=360 Participants | 4 | - |
| Vasogenic Edema/Sulcal Effusion, Baselinen=360 Participants | 0 | - |
| Cerebrovascular Pathology, Week 89 Open Label Extension (OLE)n=360 Participants | 0 | - |
| CNS Trauma, Week 89 OLEn=360 Participants | 0 | - |
| Intracranial Tumor, Week 89 OLEn=360 Participants | 1 | - |
| Lacunar Infarct, Week 89 OLEn=360 Participants | 0 | - |
| Superficial Hemosiderosis, Week 89 OLEn=360 Participants | 0 | - |
| Territorial Infarct, Week 89 OLEn=360 Participants | 0 | - |
| Vasogenic Edema/Sulcal Effusion, Week 89 OLEn=360 Participants | 1 | - |
Safety / tolerability / PK
2 endpointsPrimary/protocol endpoint
Percentage of Participants With Adverse Events
Time frame:Up to the data cutoff date 15 January 2021 (up to approximately 39 months)
threshold achievement, event
Primary/registry result
Percentage of Participants With Adverse Events
Time frame:Up to the data cutoff date 15 January 2021 (up to approximately 39 months)
threshold achievement, event
Posted result
| Group | Value (number), Percentage of participants | Reported bounds |
|---|---|---|
| Placebo Double Blind Periodn=130 Participants | 93.1 | - |
| Dose 1 Semorinemab Double Blind Periodn=89 Participants | 88.8 | - |
| Dose 2 Semorinemab Double Blind Periodn=132 Participants | 94.7 | - |
| Dose 3 Semorinemab Double Blind Periodn=90 Participants | 92.2 | - |
| Dose 2 Semorinemab Open Label Extension Periodn=360 Participants | 47.5 | - |
Other (unclassified)
8 endpointsPrimary/protocol endpoint/low confidence
Change From Baseline on the C-SSRS
Time frame:Baseline to data cutoff date 15 January 2021 (up to approximately 39 months)
change from baseline, improvement
Primary/registry result/low confidence
Change From Baseline on the C-SSRS
Time frame:Baseline to data cutoff date 15 January 2021 (up to approximately 39 months)
change from baseline, improvement
Posted result
| Group | Value (count_of_participants), Participants | Reported bounds |
|---|---|---|
| Placebo Double Blind PeriodMissing/No Eventsn=130 Participants | 1 | - |
| Missing/SI1n=130 Participants | 0 | - |
| Missing/SI2n=130 Participants | 0 | - |
| Missing/SI3n=130 Participants | 0 | - |
| Missing/SI4n=130 Participants | 0 | - |
| Missing/Missingn=130 Participants | 0 | - |
| No Event/No Eventn=130 Participants | 119 | - |
| No Event/SI1n=130 Participants | 3 | - |
| No Event/ SI2n=130 Participants | 0 | - |
| No Event/SI3n=130 Participants | 0 | - |
| No Event/ SI4n=130 Participants | 0 | - |
| No Event/ Missingn=130 Participants | 1 | - |
| SI1/No Eventn=130 Participants | 3 | - |
| SI1/SI1n=130 Participants | 0 | - |
| SI1/SI2n=130 Participants | 1 | - |
| SI1/SI3n=130 Participants | 0 | - |
| SI1/SI4n=130 Participants | 1 | - |
| SI1/Missingn=130 Participants | 0 | - |
| SI2/No Eventn=130 Participants | 0 | - |
| SI2/SI1n=130 Participants | 0 | - |
| SI2/SI2n=130 Participants | 0 | - |
| SI2/SI3n=130 Participants | 0 | - |
| SI2/SI4n=130 Participants | 0 | - |
| SI2/Missingn=130 Participants | 0 | - |
| SI3/No Eventn=130 Participants | 1 | - |
| SI3/SI1n=130 Participants | 0 | - |
| SI3/SI2n=130 Participants | 0 | - |
| SI3/SI3n=130 Participants | 0 | - |
| SI3/SI4n=130 Participants | 0 | - |
| SI3/Missingn=130 Participants | 0 | - |
| SI4/No Eventn=130 Participants | 0 | - |
| SI4/SI1n=130 Participants | 0 | - |
| SI4/SI2n=130 Participants | 0 | - |
| SI4/SI3n=130 Participants | 0 | - |
| SI4/Missingn=130 Participants | 0 | - |
| Dose 1 Semorinemab Double Blind PeriodMissing/No Eventsn=89 Participants | 1 | - |
| Missing/SI1n=89 Participants | 0 | - |
| Missing/SI2n=89 Participants | 0 | - |
| Missing/SI3n=89 Participants | 0 | - |
| Missing/SI4n=89 Participants | 0 | - |
| Missing/Missingn=89 Participants | 0 | - |
| No Event/No Eventn=89 Participants | 80 | - |
| No Event/SI1n=89 Participants | 3 | - |
| No Event/ SI2n=89 Participants | 1 | - |
| No Event/SI3n=89 Participants | 0 | - |
| No Event/ SI4n=89 Participants | 0 | - |
| No Event/ Missingn=89 Participants | 0 | - |
| SI1/No Eventn=89 Participants | 3 | - |
| SI1/SI1n=89 Participants | 0 | - |
| SI1/SI2n=89 Participants | 0 | - |
| SI1/SI3n=89 Participants | 0 | - |
| SI1/SI4n=89 Participants | 0 | - |
| SI1/Missingn=89 Participants | 0 | - |
| SI2/No Eventn=89 Participants | 1 | - |
| SI2/SI1n=89 Participants | 0 | - |
| SI2/SI2n=89 Participants | 0 | - |
| SI2/SI3n=89 Participants | 0 | - |
| SI2/SI4n=89 Participants | 0 | - |
| SI2/Missingn=89 Participants | 0 | - |
| SI3/No Eventn=89 Participants | 0 | - |
| SI3/SI1n=89 Participants | 0 | - |
| SI3/SI2n=89 Participants | 0 | - |
| SI3/SI3n=89 Participants | 0 | - |
| SI3/SI4n=89 Participants | 0 | - |
| SI3/Missingn=89 Participants | 0 | - |
| SI4/No Eventn=89 Participants | 0 | - |
| SI4/SI1n=89 Participants | 0 | - |
| SI4/SI2n=89 Participants | 0 | - |
| SI4/SI3n=89 Participants | 0 | - |
| SI4/Missingn=89 Participants | 0 | - |
| Dose 2 Semorinemab Double Blind PeriodMissing/No Eventsn=132 Participants | 2 | - |
| Missing/SI1n=132 Participants | 0 | - |
| Missing/SI2n=132 Participants | 0 | - |
| Missing/SI3n=132 Participants | 0 | - |
| Missing/SI4n=132 Participants | 0 | - |
| Missing/Missingn=132 Participants | 0 | - |
| No Event/No Eventn=132 Participants | 123 | - |
| No Event/SI1n=132 Participants | 2 | - |
| No Event/ SI2n=132 Participants | 1 | - |
| No Event/SI3n=132 Participants | 0 | - |
| No Event/ SI4n=132 Participants | 0 | - |
| No Event/ Missingn=132 Participants | 0 | - |
| SI1/No Eventn=132 Participants | 1 | - |
| SI1/SI1n=132 Participants | 0 | - |
| SI1/SI2n=132 Participants | 0 | - |
| SI1/SI3n=132 Participants | 0 | - |
| SI1/SI4n=132 Participants | 0 | - |
| SI1/Missingn=132 Participants | 0 | - |
| SI2/No Eventn=132 Participants | 2 | - |
| SI2/SI1n=132 Participants | 1 | - |
| SI2/SI2n=132 Participants | 0 | - |
| SI2/SI3n=132 Participants | 0 | - |
| SI2/SI4n=132 Participants | 0 | - |
| SI2/Missingn=132 Participants | 0 | - |
| SI3/No Eventn=132 Participants | 0 | - |
| SI3/SI1n=132 Participants | 0 | - |
| SI3/SI2n=132 Participants | 0 | - |
| SI3/SI3n=132 Participants | 0 | - |
| SI3/SI4n=132 Participants | 0 | - |
| SI3/Missingn=132 Participants | 0 | - |
| SI4/No Eventn=132 Participants | 0 | - |
| SI4/SI1n=132 Participants | 0 | - |
| SI4/SI2n=132 Participants | 0 | - |
| SI4/SI3n=132 Participants | 0 | - |
| SI4/Missingn=132 Participants | 0 | - |
| Dose 3 Semorinemab Double Blind PeriodMissing/No Eventsn=90 Participants | 0 | - |
| Missing/SI1n=90 Participants | 0 | - |
| Missing/SI2n=90 Participants | 0 | - |
| Missing/SI3n=90 Participants | 0 | - |
| Missing/SI4n=90 Participants | 0 | - |
| Missing/Missingn=90 Participants | 0 | - |
| No Event/No Eventn=90 Participants | 83 | - |
| No Event/SI1n=90 Participants | 4 | - |
| No Event/ SI2n=90 Participants | 0 | - |
| No Event/SI3n=90 Participants | 0 | - |
| No Event/ SI4n=90 Participants | 0 | - |
| No Event/ Missingn=90 Participants | 1 | - |
| SI1/No Eventn=90 Participants | 1 | - |
| SI1/SI1n=90 Participants | 0 | - |
| SI1/SI2n=90 Participants | 0 | - |
| SI1/SI3n=90 Participants | 0 | - |
| SI1/SI4n=90 Participants | 0 | - |
| SI1/Missingn=90 Participants | 0 | - |
| SI2/No Eventn=90 Participants | 0 | - |
| SI2/SI1n=90 Participants | 0 | - |
| SI2/SI2n=90 Participants | 1 | - |
| SI2/SI3n=90 Participants | 0 | - |
| SI2/SI4n=90 Participants | 0 | - |
| SI2/Missingn=90 Participants | 0 | - |
| SI3/No Eventn=90 Participants | 0 | - |
| SI3/SI1n=90 Participants | 0 | - |
| SI3/SI2n=90 Participants | 0 | - |
| SI3/SI3n=90 Participants | 0 | - |
| SI3/SI4n=90 Participants | 0 | - |
| SI3/Missingn=90 Participants | 0 | - |
| SI4/No Eventn=90 Participants | 0 | - |
| SI4/SI1n=90 Participants | 0 | - |
| SI4/SI2n=90 Participants | 0 | - |
| SI4/SI3n=90 Participants | 0 | - |
| SI4/Missingn=90 Participants | 0 | - |
| Dose 2 Semorinemab Open Label Extension PeriodMissing/No Eventsn=360 Participants | 3 | - |
| Missing/SI1n=360 Participants | 0 | - |
| Missing/SI2n=360 Participants | 0 | - |
| Missing/SI3n=360 Participants | 0 | - |
| Missing/SI4n=360 Participants | 0 | - |
| Missing/Missingn=360 Participants | 0 | - |
| No Event/No Eventn=360 Participants | 336 | - |
| No Event/SI1n=360 Participants | 5 | - |
| No Event/ SI2n=360 Participants | 1 | - |
| No Event/SI3n=360 Participants | 0 | - |
| No Event/ SI4n=360 Participants | 0 | - |
| No Event/ Missingn=360 Participants | 1 | - |
| SI1/No Eventn=360 Participants | 8 | - |
| SI1/SI1n=360 Participants | 1 | - |
| SI1/SI2n=360 Participants | 0 | - |
| SI1/SI3n=360 Participants | 0 | - |
| SI1/SI4n=360 Participants | 0 | - |
| SI1/Missingn=360 Participants | 0 | - |
| SI2/No Eventn=360 Participants | 1 | - |
| SI2/SI1n=360 Participants | 2 | - |
| SI2/SI2n=360 Participants | 0 | - |
| SI2/SI3n=360 Participants | 0 | - |
| SI2/SI4n=360 Participants | 0 | - |
| SI2/Missingn=360 Participants | 0 | - |
| SI3/No Eventn=360 Participants | 1 | - |
| SI3/SI1n=360 Participants | 0 | - |
| SI3/SI2n=360 Participants | 0 | - |
| SI3/SI3n=360 Participants | 0 | - |
| SI3/SI4n=360 Participants | 0 | - |
| SI3/Missingn=360 Participants | 0 | - |
| SI4/No Eventn=360 Participants | 0 | - |
| SI4/SI1n=360 Participants | 0 | - |
| SI4/SI2n=360 Participants | 0 | - |
| SI4/SI3n=360 Participants | 1 | - |
| SI4/Missingn=360 Participants | 0 | - |
Secondary/protocol endpoint/low confidence
Change From Baseline on the Amsterdam Instrumental Activity of Daily Living (iADL) Questionnaire
Time frame:Baseline and 73 weeks
change from baseline, improvement
Secondary/protocol endpoint/low confidence
Serum Concentrations of Semorinemab at Specified Timepoints
Time frame:Up to 109 weeks
concentration, descriptive
Secondary/protocol endpoint/low confidence
Presence of Anti-drug Antibodies During the Study Relative to Their Presence at Baseline
Time frame:Up to 109 weeks
descriptive
Secondary/registry result/low confidence
Change From Baseline on the Amsterdam Instrumental Activity of Daily Living (iADL) Questionnaire
Time frame:Baseline and 73 weeks
change from baseline, improvement
Posted result
| Group | Value (mean), Score on a scale | Standard error |
|---|---|---|
| Placebo Double Blind Periodn=95 Participants | -6.59 | 0.856 |
| Dose 1 Semorinemab Double Blind Periodn=70 Participants | -6.55 | 0.999 |
| Dose 2 Semorinemab Double Blind Periodn=109 Participants | -6.92 | 0.824 |
| Dose 3 Semorinemab Double Blind Periodn=67 Participants | -7.31 | 1.013 |
p0.9749Mixed-effect Model Repeated Measures
p0.7718Mixed-effect Model Repeated Measures
p0.5789Mixed-effect Model Repeated Measures
Secondary/registry result/low confidence
Serum Concentrations of Semorinemab at Specified Timepoints
Time frame:Up to 109 weeks
concentration, descriptive
Posted result
| Group | Value (mean), ug/mL | Standard deviation |
|---|---|---|
| Dose 1 Semorinemab Double Blind and Open Label Extension PeriodsWeek 1, 0-4 Hours Predosen=87 Participants | NA | NA |
| Week 1, 1 Hour Postdosen=87 Participants | 472 | 131 |
| Week 1, 2 Hours Postdosen=86 Participants | 476 | 123 |
| Week 1, 4 Hours postdosen=86 Participants | 463 | 135 |
| Week 3, 0-4 hours Predosen=89 Participants | 184 | 52.7 |
| Week 3, 30 min Post dosen=88 Participants | 718 | 198 |
| Week 5, 0-4 Hours Predosen=88 Participants | 318 | 81.5 |
| Week 5, 30 min Postdosen=86 Participants | 908 | 508 |
| Week 9, 0-4 hours Predosen=88 Participants | 344 | 128 |
| Week 9, 30 Minutes Postdosen=89 Participants | 889 | 321 |
| Week 13, 0-4 Hours Predosen=87 Participants | 360 | 105 |
| Week 13, 30 Minutes Postdosen=86 Participants | 998 | 896 |
| Week 17, 0-4 Hours Predosen=84 Participants | 386 | 116 |
| Week 17, 30 Minutes Postdosen=84 Participants | 819 | 242 |
| Week 33, 0-4 Hours Predosen=83 Participants | 404 | 134 |
| Week 33, 30 Minutes Postdosen=82 Participants | 801 | 260 |
| Week 49, 0-4 Hours Predosen=78 Participants | 377 | 105 |
| Week 49, 30 Minutes Postdosen=77 Participants | 871 | 260 |
| Week 65, 0-4 Hours Predosen=67 Participants | 405 | 127 |
| Week 65, 30 Minutes Postdosen=67 Participants | 963 | 401 |
| Week 73n=71 Participants | 327 | 154 |
| Week 77 OLE, 0-4 Hours Predosen=13 Participants | 180 | 71.0 |
| Week 77 OLE, 1 hour Postdosen=12 Participants | 1700 | 523 |
| Week 77 OLE, 2 hours Postdosen=13 Participants | 1830 | 552 |
| Week 77 OLE, 4 hours Postdosen=11 Participants | 1850 | 516 |
| Week 93 OLE, 0-4 Hours Pre-dosen=2 Participants | 632 | 37.5 |
| Week 93 OLE, 30 Minutes Postdosen=2 Participants | 1920 | 431 |
| Dose 2 Semorinemab Double Blind and Open Label Extension PeriodsWeek 1, 0-4 Hours Predosen=132 Participants | NA | NA |
| Week 1, 1 Hour Postdosen=132 Participants | 1580 | 496 |
| Week 1, 2 Hours Postdosen=130 Participants | 1510 | 419 |
| Week 1, 4 Hours postdosen=128 Participants | 1370 | 405 |
| Week 3, 0-4 hours Predosen=131 Participants | 601 | 211 |
| Week 3, 30 min Post dosen=130 Participants | 2320 | 581 |
| Week 5, 0-4 Hours Predosen=131 Participants | 955 | 256 |
| Week 5, 30 min Postdosen=130 Participants | 2780 | 695 |
| Week 9, 0-4 hours Predosen=130 Participants | 961 | 288 |
| Week 9, 30 Minutes Postdosen=129 Participants | 2790 | 757 |
| Week 13, 0-4 Hours Predosen=128 Participants | 1060 | 333 |
| Week 13, 30 Minutes Postdosen=127 Participants | 2900 | 668 |
| Week 17, 0-4 Hours Predosen=127 Participants | 1040 | 316 |
| Week 17, 30 Minutes Postdosen=126 Participants | 2930 | 902 |
| Week 33, 0-4 Hours Predosen=126 Participants | 960 | 277 |
| Week 33, 30 Minutes Postdosen=126 Participants | 2540 | 853 |
| Week 49, 0-4 Hours Predosen=119 Participants | 1060 | 332 |
| Week 49, 30 Minutes Postdosen=117 Participants | 2810 | 967 |
| Week 65, 0-4 Hours Predosen=101 Participants | 1170 | 276 |
| Week 65, 30 Minutes Postdosen=100 Participants | 2930 | 830 |
| Week 73n=104 Participants | 1030 | 451 |
| Week 73, 0-4 Hours Predosen=1 Participants | 382 | NA |
| Week 73, 1 Hour Postdosen=1 Participants | 1910 | NA |
| Week 73, 2 Hours Postdosen=1 Participants | 1740 | NA |
| Week 73, 4 Hours Postdosen=1 Participants | 1710 | NA |
| Week 77 OLE, 0-4 Hours Predosen=20 Participants | 724 | 167 |
| Week 77 OLE, 1 hour Postdosen=20 Participants | 2460 | 868 |
| Week 77 OLE, 2 hours Postdosen=20 Participants | 2270 | 442 |
| Week 77 OLE, 4 hours Postdosen=20 Participants | 2270 | 480 |
| Week 93 OLE, 0-4 Hours Pre-dosen=2 Participants | 1040 | 113 |
| Week 93 OLE, 30 Minutes Postdosen=2 Participants | 2570 | 91.9 |
| Week 109 OLE, 0-4 Hours Predosen=1 Participants | 1270 | NA |
| Week 109 OLE, 30 Minutes Postdosen=1 Participants | 3330 | NA |
| Dose 3 Semorinemab Double Blind and Open Label Extension PeriodsWeek 1, 0-4 Hours Predosen=90 Participants | NA | NA |
| Week 1, 1 Hour Postdosen=90 Participants | 2690 | 689 |
| Week 1, 2 Hours Postdosen=90 Participants | 2600 | 707 |
| Week 1, 4 Hours postdosen=89 Participants | 2570 | 785 |
| Week 3, 0-4 hours Predosen=89 Participants | 1100 | 449 |
| Week 3, 30 min Post dosen=88 Participants | 4190 | 1010 |
| Week 5, 0-4 Hours Predosen=87 Participants | 1920 | 614 |
| Week 5, 30 min Postdosen=85 Participants | 4860 | 1250 |
| Week 9, 0-4 hours Predosen=83 Participants | 1840 | 513 |
| Week 9, 30 Minutes Postdosen=85 Participants | 4960 | 1270 |
| Week 13, 0-4 Hours Predosen=86 Participants | 1910 | 545 |
| Week 13, 30 Minutes Postdosen=86 Participants | 4880 | 1250 |
| Week 17n=1 Participants | 1750 | NA |
| Week 17, 0-4 Hours Predosen=83 Participants | 1890 | 522 |
| Week 17, 30 Minutes Postdosen=86 Participants | 4770 | 1270 |
| Week 33, 0-4 Hours Predosen=83 Participants | 2050 | 648 |
| Week 33, 30 Minutes Postdosen=80 Participants | 4800 | 1200 |
| Week 49, 0-4 Hours Predosen=79 Participants | 2160 | 605 |
| Week 49, 30 Minutes Postdosen=80 Participants | 4960 | 1030 |
| Week 65n=1 Participants | 2100 | NA |
| Week 65, 0-4 Hours Predosen=66 Participants | 2020 | 681 |
| Week 65, 30 Minutes Postdosen=67 Participants | 4710 | 1450 |
| Week 73n=69 Participants | 1830 | 752 |
| Week 77 OLE, 0-4 Hours Predosen=13 Participants | 1030 | 345 |
| Week 77 OLE, 1 hour Postdosen=12 Participants | 2670 | 707 |
| Week 77 OLE, 2 hours Postdosen=13 Participants | 2510 | 579 |
| Week 77 OLE, 4 hours Postdosen=12 Participants | 2790 | 558 |
| Week 93 OLE, 0-4 Hours Pre-dosen=4 Participants | 1290 | 307 |
| Week 93 OLE, 30 Minutes Postdosen=4 Participants | 2880 | 492 |
Secondary/registry result/low confidence
Presence of Anti-drug Antibodies During the Study Relative to Their Presence at Baseline
Time frame:Up to 109 weeks
descriptive
Posted result
| Group | Value (number), Percentage of participants | Reported bounds |
|---|---|---|
| Placebo Double Blind PeriodBaselinen=127 Participants | 0 | - |
| Dose 1 Semorinemab Double Blind PeriodBaselinen=87 Participants | 0 | - |
| Post-baselinen=86 Participants | 0 | - |
| Dose 2 Semorinemab Double Blind PeriodBaselinen=132 Participants | 0 | - |
| Post-baselinen=128 Participants | 0 | - |
| Dose 3 Semorinemab Double Blind PeriodBaselinen=90 Participants | 0 | - |
| Post-baselinen=88 Participants | 0 | - |
Publications (6)
Bibliography
Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.
Registry references + supporting bibliography
- PMID35696185via DERIVED
- PMID36641609via DERIVED
- PMID39513754via DERIVED
- PMID37325545via DERIVED
- PMID40603145via DERIVED
- PMID38606196via DERIVED
Provenance
Sources
Trial identity, design, statusClinicalTrials.gov API v2
Snapshot dateJuly 21, 2026
Endpoint classificationDelfa ADRD endpoint taxonomy
Results tableClinicalTrials.gov results section
Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.