CompletedPhase 2Results posted

A Study of Semorinemab in Patients With Moderate Alzheimer's Disease

A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study of MTAU9937A in Patients With Moderate Alzheimer's Disease

Lead sponsor

Genentech, Inc.

Asset

Semorinemab

Listed sites

Recruiting sites

Enrollment

272

actual

Study population

Alzheimer’s disease

Key I/E criteria

•Alzheimer's disease•Amyloid biomarker required (PET/CSF)•MMSE 16-21•MRI contraindications excluded

Primary endpoints

•ADAS-Cog•ADCS-Activities of Daily Living (ADCS-ADL)

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

Org study IDGN40040

NCT IDNCT03828747

Timeline

Milestones

Study start2019-01-25actual

Study first posted2019-02-04actual

Primary completion2021-07-20actual

Results first posted2022-10-03actual

Study completion2023-08-30actual

Last update posted2024-09-24actual

Assets

Drug assets

Semorinemab

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age50 Years

Maximum age85 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•National Institute on Aging/Alzheimer's Association core clinical criteria for probable AD dementia

•Evidence of the AD pathological process, by a positive amyloid assessment either on CSF Aβ1-42 as measured on Elecsys β-Amyloid(1-42) Test System OR amyloid PET scan

•AD dementia of moderate severity, as defined by a screening MMSE score of 16-21 points, inclusive, and a CDR-GS of 1 or 2

•Availability of a person with sufficient contact with the participant to be able to provide accurate information on the participant's cognitive, behavioral and functional ability

Exclusion criteria

•Pregnant or breastfeeding

•Inability to tolerate MRI procedures or contraindication to MRI

•Contraindication to PET imaging

•Residence in a skilled nursing facility

•Any serious medical condition or abnormality in clinical laboratory tests that, 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

•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, or any passive immunotherapy against tau

•Use of any passive immunotherapy (immunoglobulin) against Aβ, unless the last dose was at least 1 year prior to screening or any active immunotherapy (vaccine) that is under evaluation to prevent or postpone cognitive decline

•Any other biologic therapy or previous treatment with medications specifically intended to treat Parkinsonian symptoms or any other non-AD 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): 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 (28)

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

Global cognition

Other (unclassified)

Function / daily living

Safety / tolerability / PK

Global cognition

12 endpoints

Primary/protocol endpoint

Change From Baseline to Last Visit of Double-Blind Treatment Period in Cognitive Function as Measured by the Alzheimer's Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11)

Time frame:Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2

ADAS-Cog

change from baseline, improvement

Primary/registry result

Change From Baseline to Last Visit of Double-Blind Treatment Period in Cognitive Function as Measured by the Alzheimer's Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11)

Time frame:Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a scale	Standard error
SemorinemabBaselinen=123 Participants	23.93	0.533
Change from Baseline at Week 49 (includes Cohort 1 and 2)n=102 Participants	3.96	0.658
Change from Baseline at Week 61 (only Cohort 2)n=38 Participants	5.71	0.907
PlaceboBaselinen=115 Participants	24.09	0.589
Change from Baseline at Week 49 (includes Cohort 1 and 2)n=96 Participants	6.85	0.643
Change from Baseline at Week 61 (only Cohort 2)n=30 Participants	8.47	0.965

Least Squares Mean Difference-2.8995% CI-4.56 - -1.21p0.0008Mixed Models Analysis

Change from Baseline at Week 49

Least Squares Mean Difference-2.7595% CI-5.31 - -0.20p0.0351Mixed Models Analysis

Change from Baseline at Week 61

Secondary/protocol endpoint

Change From Baseline to Last Visit of Double-Blind Treatment Period on the Clinical Dementia Rating-Sum of Boxes (CDR-SB)

Time frame:Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE)

Time frame:Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Secondary/protocol endpoint

Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period in Cognitive Function as Measured by the Alzheimer's Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11)

Time frame:Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period on the Clinical Dementia Rating-Sum of Boxes (CDR-SB)

Time frame:Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Secondary/protocol endpoint

Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE)

Time frame:Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Secondary/registry result

Change From Baseline to Last Visit of Double-Blind Treatment Period on the Clinical Dementia Rating-Sum of Boxes (CDR-SB)

Time frame:Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a scale	Standard error
SemorinemabBaselinen=123 Participants	6.23	0.156
Change from Baseline at Week 49 (includes Cohort 1 and 2)n=109 Participants	1.80	0.217
Change from Baseline at Week 61 (only Cohort 2)n=40 Participants	2.45	0.367
PlaceboBaselinen=115 Participants	6.51	0.182
Change from Baseline at Week 49 (includes Cohort 1 and 2)n=101 Participants	1.54	0.214
Change from Baseline at Week 61 (only Cohort 2)n=33 Participants	2.28	0.393

Least Squares Mean Difference0.2695% CI-0.29 - 0.82p0.3501Mixed Models Analysis

Change from Baseline at Week 49

Least Squares Mean Difference0.1795% CI-0.87 - 1.22p0.7431Mixed Models Analysis

Change from Baseline at Week 61

Secondary/registry result

Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE)

Time frame:Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a scale	Standard error
SemorinemabBaselinen=123 Participants	18.38	0.182
Change from Baseline at Week 49 (includes Cohort 1 and 2)n=105 Participants	-2.86	0.330
Change from Baseline at Week 61 (only Cohort 2)n=39 Participants	-3.14	0.429
PlaceboBaselinen=115 Participants	18.15	0.197
Change from Baseline at Week 49 (includes Cohort 1 and 2)n=97 Participants	-3.12	0.325
Change from Baseline at Week 61 (only Cohort 2)n=29 Participants	-4.22	0.466

Least Squares Mean Difference0.2795% CI-0.58 - 1.11p0.5366Mixed Models Analysis

Change from Baseline at Week 49

Least Squares Mean Difference1.0895% CI-0.15 - 2.30p0.0851Mixed Models Analysis

Change from Baseline at Week 61

Secondary/registry result

Time frame:Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Semorinemabn=135 Participants	NA	-
Placebon=132 Participants	NA	-

Secondary/registry result

Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period on the Clinical Dementia Rating-Sum of Boxes (CDR-SB)

Time frame:Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Semorinemabn=135 Participants	NA	-
Placebon=132 Participants	NA	-

Secondary/registry result

Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE)

Time frame:Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Semorinemabn=135 Participants	NA	-
Placebon=132 Participants	NA	-

Function / daily living

4 endpoints

Primary/protocol endpoint

Change From Baseline to Last Visit of Double-Blind Treatment Period in Functional Capacities as Measured by the Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL)

Time frame:Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Primary/registry result

Change From Baseline to Last Visit of Double-Blind Treatment Period in Functional Capacities as Measured by the Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL)

Time frame:Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a scale	Standard error
SemorinemabBaselinen=123 Participants	62.03	0.764
Change from Baseline at Week 49 (includes Cohort 1 and 2)n=107 Participants	-7.63	1.002
Change from Baseline at Week 61 (only Cohort 2)n=40 Participants	-9.29	1.343
PlaceboBaselinen=115 Participants	59.74	0.842
Change from Baseline at Week 49 (includes Cohort 1 and 2)n=101 Participants	-6.80	0.974
Change from Baseline at Week 61 (only Cohort 2)n=33 Participants	-7.57	1.462

Least Squares Mean Difference-0.8395% CI-3.39 - 1.72p0.5207Mixed Models Analysis

Change from Baseline at Week 49

Least Squares Mean Difference-1.7295% CI-5.50 - 2.07p0.3704Mixed Models Analysis

Change from Baseline at Week 61

Secondary/protocol endpoint

Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period in Functional Capacities as Measured by the Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL)

Time frame:Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Secondary/registry result

Time frame:Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Semorinemabn=135 Participants	NA	-
Placebon=132 Participants	NA	-

Safety / tolerability / PK

4 endpoints

Secondary/protocol endpoint

Percentage of Participants With Adverse Events

Time frame:Baseline up to end of study (approximately 4 years and 7 months)

threshold achievement, event

Secondary/protocol endpoint

Relationship Between ADA Status and Percentage of Participants With Adverse Events

Time frame:Up to 57 weeks for Cohort 1, and up to 69 weeks for Cohort 2.

threshold achievement, event

Secondary/registry result

Percentage of Participants With Adverse Events

Time frame:Baseline up to end of study (approximately 4 years and 7 months)

threshold achievement, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Semorinemabn=135 Participants	112	-
Placebon=132 Participants	107	-
Semorinemab (Open-label Extension)n=199 Participants	170	-

Secondary/registry result

Relationship Between ADA Status and Percentage of Participants With Adverse Events

Time frame:Up to 57 weeks for Cohort 1, and up to 69 weeks for Cohort 2.

threshold achievement, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Semorinemabn=135 Participants	NA	-
Placebon=132 Participants	NA	-

Other (unclassified)

8 endpoints

Secondary/protocol endpoint/low confidence

Serum Concentration of RO7105705 at Specified Timepoints

Time frame:Weeks 1,3,5,9,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,3,5,9,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.

concentration, descriptive

Secondary/protocol endpoint/low confidence

Incidence of Anti-drug Antibodies (ADAs) During the Study Relative to the Prevalence of ADAs at Baseline

Time frame:Weeks 1,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.

event count, event

Secondary/protocol endpoint/low confidence

Relationship Between ADA Status and Serum Concentration of RO7105705 at Specified Timepoints

Time frame:Weeks 1,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.

concentration, descriptive

Secondary/protocol endpoint/low confidence

Relationship Between ADA Status and Incidence of Anti-Drug Antibodies (ADAs) During the Study Relative to the Prevalence of ADAs at Baseline

Time frame:Weeks 1,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.

event count, event

Secondary/registry result/low confidence

Serum Concentration of RO7105705 at Specified Timepoints

Time frame:Weeks 1,3,5,9,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,3,5,9,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.

concentration, descriptive

Posted result

Group	Value (geometric_mean), Microgram per milliliter (µg/ml)	Geometric coefficient of variation
SemorinemabWeek 1 predosen=130 Participants	NA	NA
Week 1 postdosen=129 Participants	1610	27.9
Week 3 predosen=127 Participants	546	32.1
Week 3 postdosen=128 Participants	1980	32.6
Week 5 predosen=127 Participants	951	30.4
Week 5 postdosen=125 Participants	2260	47.0
Week 9 predosen=116 Participants	935	32.2
Week 9 postdosen=117 Participants	2520	27.2
Week 13 predosen=118 Participants	943	32.9
Week 13 postdosen=114 Participants	2480	31.2
Week 25 predosen=110 Participants	996	37.1
Week 25 postdosen=108 Participants	2420	37.9
Week 37 predosen=107 Participants	981	45.4
Week 37 postdosen=107 Participants	2430	31.1
Week 49 predosen=101 Participants	1020	35.2
Week 49 postdosen=36 Participants	2650	34.2
Week 61n=40 Participants	1100	26.8

Secondary/registry result/low confidence

Incidence of Anti-drug Antibodies (ADAs) During the Study Relative to the Prevalence of ADAs at Baseline

Time frame:Weeks 1,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
SemorinemabBaseline (BL) - positive samplen=133 Participants	0	-
BL - negative samplen=133 Participants	133	-
Post-BL - positive treatment emergent ADAn=128 Participants	0	-
Post-BL - negative treatment emergent ADAn=128 Participants	128	-
PlaceboBaseline (BL) - positive samplen=129 Participants	1	-
BL - negative samplen=129 Participants	128	-

Secondary/registry result/low confidence

Relationship Between ADA Status and Serum Concentration of RO7105705 at Specified Timepoints

Time frame:Weeks 1,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.

concentration, descriptive

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Semorinemabn=135 Participants	NA	-
Placebon=132 Participants	NA	-

Secondary/registry result/low confidence

Relationship Between ADA Status and Incidence of Anti-Drug Antibodies (ADAs) During the Study Relative to the Prevalence of ADAs at Baseline

Time frame:Weeks 1,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
SemorinemabPositive Sample at BLn=135 Participants	0	-
Positive Sample post BLn=135 Participants	NA	-
PlaceboPositive Sample at BLn=132 Participants	1	-
Positive Sample post BLn=132 Participants	NA	-

Publications (3)

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

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.