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This Phase II, multicenter, randomized, double-blind, placebo-controlled, parallel-group study will evaluate the clinical efficacy, safety, pharmacokinetics, and pharmacodynamics of semorinemab in patients with moderate AD. The study consists of a screening period, a double-blind treatment period, an optional open-label extension (OLE) period, and a safety follow-up period. There may be up to two study cohorts.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Semorinemab | Experimental | Semorinemab will be administered intravenously in the double-blind treatment period, and semorinemab will be administered intravenously in the optional open-label extension period. |
|
| Placebo | Placebo Comparator | Placebo will be administered intravenously in the double-blind treatment period and semorinemab will be administered intravenously in the optional open-label extension. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Semorinemab | Drug | Participants will receive semorinemab every 2 weeks (Q2W) for the first three doses of the double-blind treatment period and every 4 weeks (Q4W) thereafter during the double-blind treatment period. Semorinemab will be administered Q4W in the OLE period. |
| Measure | Description | Time Frame |
|---|---|---|
| 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) | The Alzheimer's Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11) is an 11 item cognitive subscale used to quantify the areas of cognitive function most often affected in Alzheimer's disease. The total score ranges from 0-70 with lower scores indicating better cognitive function. | Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2 |
| 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) | The Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL) is a scale used to quantify performance of activities of daily living (ADL). Scores on the ADCS-ADL range from 0-78, with higher scores indicating better ADL function. | Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to Last Visit of Double-Blind Treatment Period on the Clinical Dementia Rating-Sum of Boxes (CDR-SB) | The Clinical Dementia Rating-Sum of Boxes (CDR-SB) is a scale used to quantify the severity of symptoms of dementia. The CDR-SB is obtained through interviews of patients and informants, and disease severity is rated in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a 5-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment (personal care is scored on a 4-point scale without a 0.5 rating available). The CDR-SB score is obtained by summing each of the domain box scores, with scores ranging from 0 to 18, with the higher values representing more severe impairment. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Collaborative Neuroscience Network, Inc. | Garden Grove | California | 92845 | United States | ||
| Pharmacology Research Institute |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40603145 | Derived | Chandler JM, Lansdall CJ, Ye W, McDougall F, Belger M, Toth B, Mi X, Sink KM, Atkins AS. The Alzheimer's Disease Cooperative Study - Activities of Daily Living dependence score: revision and validation of an algorithm evaluating patient dependence across the spectrum of AD severity. J Prev Alzheimers Dis. 2025 Sep;12(8):100261. doi: 10.1016/j.tjpad.2025.100261. Epub 2025 Jul 1. | |
| 39513754 |
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Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm)
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A total of 272 participants were enrolled at 49 centers.
The study was conducted at 49 centers in 4 countries.
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| ID | Title | Description |
|---|---|---|
| FG000 | Semorinemab | Semorinemab was administered intravenously in the double-blind treatment period and was administered intravenously in the optional open-label extension period. |
| FG001 | Placebo |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Double-Blind Treatment Period |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 14, 2021 |
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|
| Placebo | Drug | Participants will receive placebo every 2 weeks (Q2W) for the first three doses of the double-blind treatment period and every 4 weeks (Q4W) thereafter during the double-blind treatment period. |
|
| [18F]GTP1 | Drug | [18F]GTP1 will be administered as a solution for intravenous (IV) use, as part of positron emission tomography (PET) imaging. |
|
| Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2 |
| Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE) | The Mini Mental State Examination (MMSE) is a brief clinical cognitive examination commonly used to screen for dementia and other cognitive deficits that has a total score of 0-30. Higher scores indicate better cognitive function. | Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2 |
| Percentage of Participants With Adverse Events | An Adverse Event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. | Baseline up to end of study (approximately 4 years and 7 months) |
| Serum Concentration of RO7105705 at Specified Timepoints | 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. |
| Incidence of Anti-drug Antibodies (ADAs) During the Study Relative to the Prevalence of ADAs at Baseline | 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. |
| Relationship Between ADA Status and Percentage of Participants With Adverse Events | Descriptive statistics will be used for assessment. | Up to 57 weeks for Cohort 1, and up to 69 weeks for Cohort 2. |
| 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) | Descriptive statistics will be used for assessment. A 70-point scale used to quantify the areas of cognitive function most often affected in Alzheimer's disease. Lower scores indicate better cognitive function. | Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2 |
| 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) | Descriptive statistics will be used for assessment. A scale used to quantify performance of activities of daily living. Scores on the ADCS-ADL range from 0-78, with higher scores indicating better ADL function. | Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2 |
| 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) | Descriptive statistics will be used for assessment. A scale used to quantify the severity of symptoms of dementia. The CDR-SB is obtained through interviews of patients and informants, and disease severity is rated in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a 5-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment (personal care is scored on a 4-point scale without a 0.5 rating available). The CDR-SOB score is obtained by summing each of the domain box scores, with scores ranging from 0 to 18, with the higher values representing more severe impairment. | Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2 |
| Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE) | Descriptive statistics will be used for assessment. The Mini Mental State Examination (MMSE) is a brief clinical cognitive examination commonly used to screen for dementia and other cognitive deficits that has a total score of 0-30. Higher scores indicate better cognitive function. | Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2 |
| Relationship Between ADA Status and Serum Concentration of RO7105705 at Specified Timepoints | Descriptive statistics will be used for assessment. | 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. |
| Relationship Between ADA Status and Incidence of Anti-Drug Antibodies (ADAs) During the Study Relative to the Prevalence of ADAs at Baseline | Descriptive statistics will be used for assessment. | 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. |
| Los Alamitos |
| California |
| 90720 |
| United States |
| Stanford University; Stanford Clinical Cancer Ctr | Palo Alto | California | 94305 | United States |
| Pacific Research Network - PRN | San Diego | California | 92103 | United States |
| Molecular Neuroimaging; MRI/PET | New Haven | Connecticut | 06510 | United States |
| KI Health Partners, LLC; New England Institute for Clinical Research | Stamford | Connecticut | 06905 | United States |
| JEM Research LLC | Atlantis | Florida | 33462 | United States |
| Bradenton Research Center | Bradenton | Florida | 34205 | United States |
| Brain Matters Research, Inc. | Delray Beach | Florida | 33445 | United States |
| Neuropsychiatric Research; Center of Southwest Florida | Fort Myers | Florida | 33912 | United States |
| Miami Jewish Health Systems | Miami | Florida | 33137 | United States |
| Collier Neurologic Specialists | Naples | Florida | 34105 | United States |
| Synexus Clinical Research US, Inc. - Orlando | Orlando | Florida | 32806 | United States |
| Alzheimer?s Research and Treatment Center | Wellington | Florida | 33414 | United States |
| Premiere Research Institute | West Palm Beach | Florida | 33407 | United States |
| Rush University Medical Center - Chicago | Chicago | Illinois | 60612 | United States |
| Alexian Brothers Neuroscience Institute | Elk Grove Village | Illinois | 60007 | United States |
| Southern Illinois University, School of Medicine | Springfield | Illinois | 62702 | United States |
| Brigham and Womens Hospital; Center for Alzheimer Research & Treatment | Boston | Massachusetts | 02115 | United States |
| Alzheimers Disease Center | Quincy | Massachusetts | 02169 | United States |
| Center for Memory and Aging | Saint Paul | Minnesota | 55130 | United States |
| Advanced Memory Research Institute of NJ | Toms River | New Jersey | 08755 | United States |
| Empire Neurology PC; MS Center of Northeastern NY | Latham | New York | 12110 | United States |
| University of Rochester; AD-CARE | Rochester | New York | 14642 | United States |
| Summit Research Network Inc. | Portland | Oregon | 97210 | United States |
| Abington Neurological Associates | Abington | Pennsylvania | 19001 | United States |
| Rhode Island Mood & Memory Research Institute | East Providence | Rhode Island | 02914 | United States |
| Butler Hospital; Movement Disorders Program | Providence | Rhode Island | 02906 | United States |
| Neurology Clinic PC | Cordova | Tennessee | 38018 | United States |
| New Orleans Center for Clinical Research | Knoxville | Tennessee | 37920 | United States |
| The Memory Clinic | Bennington | Vermont | 05201 | United States |
| Chu Toulouse | Bron | 69500 | France |
| CHU de la Timone - Hopital d Adultes; Service de Neurologie | Marseille | 13005 | France |
| Groupe Hospitalier Pitie-Salpetriere | Paris | 75651 | France |
| CHU Rennes - Hopital Pontchaillou | Rennes | 35033 | France |
| Hopital des Charpennes | Villeurbanne | 69100 | France |
| Podlaskie Centrum Psychogeriatrii | Bia?ystok | 15-756 | Poland |
| Novo-Med Zielinski i wspolnicy Sp. j. | Katowice | 40-650 | Poland |
| NZOZ NEURO-KARD Ilkowski i Partnerzy Sp. Partn. Lek | Późna | 61-853 | Poland |
| Osrodek Badan Klinicznych Euromedis | Szczecin | 70-111 | Poland |
| Centrum Medyczne NeuroProtect | Warsaw | 01-684 | Poland |
| Centrum Medyczne AMED | Warsaw | 03-291 | Poland |
| NZOZ WCA | Wroc?aw | 53-659 | Poland |
| Hospital Mutua de Terrassa | Terrassa | Barcelona | 08221 | Spain |
| Fundacio ACE | Barcelona | 08028 | Spain |
| Hospital Clinic I Provincial | Barcelona | 08036 | Spain |
| Hospital de la Santa Creu i Sant Pau; Servicio de Neurologia | Barcelona | 08041 | Spain |
| Hospital Universitario Doctor Peset | Valencia | 46017 | Spain |
| Hospital Universitari i Politecnic La Fe | Valencia | 46026 | Spain |
| Derived |
| Schauer SP, Toth B, Lee J, Honigberg LA, Ramakrishnan V, Jiang J, Kollmorgen G, Bayfield A, Wild N, Hoffman J, Ceniceros R, Dolton M, Bohorquez SMS, Hoogenraad CC, Wildsmith KR, Teng E, Monteiro C, Anania V, Yeh FL. Pharmacodynamic effects of semorinemab on plasma and CSF biomarkers of Alzheimer's disease pathophysiology. Alzheimers Dement. 2024 Dec;20(12):8855-8866. doi: 10.1002/alz.14346. Epub 2024 Nov 8. |
| 37643887 | Derived | Monteiro C, Toth B, Brunstein F, Bobbala A, Datta S, Ceniceros R, Sanabria Bohorquez SM, Anania VG, Wildsmith KR, Schauer SP, Lee J, Dolton MJ, Ramakrishnan V, Abramzon D, Teng E; Lauriet investigators. Randomized Phase II Study of the Safety and Efficacy of Semorinemab in Participants With Mild-to-Moderate Alzheimer Disease: Lauriet. Neurology. 2023 Oct 3;101(14):e1391-e1401. doi: 10.1212/WNL.0000000000207663. Epub 2023 Aug 29. |
Placebo was administered intravenously in the double-blind treatment period and semorinemab was administered intravenously in the optional open-label extension.
| Cohort 1 | Participants who completed the double-blind treatment period (before implementation of Protocol Version 3), or participants who completed the double-blind study drug treatment through Week 45 without any missed doses of study drug (after implementation of Protocol Version 4), were assigned to Cohort 1. In Cohort 1, the double-blind treatment period has a duration of 48 weeks. |
|
| Cohort 2 | Participants who were active in the double-blind treatment period (after implementation of Protocol Version 3) or participants who missed one or more study drug dose (after implementation of Protocol version 4) were assigned to Cohort 2. In Cohort 2, the double-blind treatment period has a duration of 60 weeks. |
|
| COMPLETED |
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| NOT COMPLETED |
|
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| Open-Label Extension |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Semorinemab | Semorinemab was administered intravenously in the double-blind treatment period and was administered intravenously in the optional open-label extension period. |
| BG001 | Placebo | Placebo was administered intravenously in the double-blind treatment period and semorinemab was administered intravenously in the optional open-label extension. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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) | The Alzheimer's Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11) is an 11 item cognitive subscale used to quantify the areas of cognitive function most often affected in Alzheimer's disease. The total score ranges from 0-70 with lower scores indicating better cognitive function. | The modified intent-to-treat population included all randomized participants who received at least one dose of study drug and had at least one baseline and one postbaseline ADAS-Cog11 score. | Posted | Least Squares Mean | Standard Error | Units on a scale | Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2 |
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| Primary | 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) | The Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL) is a scale used to quantify performance of activities of daily living (ADL). Scores on the ADCS-ADL range from 0-78, with higher scores indicating better ADL function. | The modified intent-to-treat population included all randomized participants who received at least one dose of study drug and had at least one baseline and one postbaseline ADAS-Cog11 and the ADCS-ADL score at the given time point. | Posted | Least Squares Mean | Standard Error | Units on a scale | Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2 |
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| Secondary | Change From Baseline to Last Visit of Double-Blind Treatment Period on the Clinical Dementia Rating-Sum of Boxes (CDR-SB) | The Clinical Dementia Rating-Sum of Boxes (CDR-SB) is a scale used to quantify the severity of symptoms of dementia. The CDR-SB is obtained through interviews of patients and informants, and disease severity is rated in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a 5-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment (personal care is scored on a 4-point scale without a 0.5 rating available). The CDR-SB score is obtained by summing each of the domain box scores, with scores ranging from 0 to 18, with the higher values representing more severe impairment. | The modified intent-to-treat population included all randomized participants who received at least one dose of study drug and had at least one baseline and one postbaseline ADAS-Cog11 and the CDR-SB score at the given time point. | Posted | Least Squares Mean | Standard Error | Units on a scale | Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2 |
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| Secondary | Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE) | The Mini Mental State Examination (MMSE) is a brief clinical cognitive examination commonly used to screen for dementia and other cognitive deficits that has a total score of 0-30. Higher scores indicate better cognitive function. | The modified intent-to-treat population included all randomized participants who received at least one dose of study drug and had at least one baseline and one postbaseline ADAS-Cog11 and the MMSE score at the given time point. | Posted | Least Squares Mean | Standard Error | Units on a scale | Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2 |
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| Secondary | Percentage of Participants With Adverse Events | An Adverse Event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. | The safety population included all randomized participants who received at least one dose of either semorinemab or placebo. | Posted | Count of Participants | Participants | Baseline up to end of study (approximately 4 years and 7 months) |
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| Secondary | Serum Concentration of RO7105705 at Specified Timepoints | The pharmacokinetic(PK)-evaluable population included all safety-evaluable participants with at least 1 post-dose serum PK sample | Posted | Geometric Mean | Geometric Coefficient of Variation | Microgram per milliliter (µg/ml) | 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. |
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| Secondary | Incidence of Anti-drug Antibodies (ADAs) During the Study Relative to the Prevalence of ADAs at Baseline | Participants with at least one predose and one postdose ADA assessment were included in this analysis. | Posted | Count of Participants | Participants | 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. |
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| Secondary | Relationship Between ADA Status and Percentage of Participants With Adverse Events | Descriptive statistics will be used for assessment. | Participants with at least one predose and one postdose ADA assessment were included in this analysis. | Posted | Count of Participants | Participants | Up to 57 weeks for Cohort 1, and up to 69 weeks for Cohort 2. |
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| Secondary | 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) | Descriptive statistics will be used for assessment. A 70-point scale used to quantify the areas of cognitive function most often affected in Alzheimer's disease. Lower scores indicate better cognitive function. | Participants with at least one predose and one postdose ADA assessment were included in this analysis. | Posted | Count of Participants | Participants | Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2 |
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| Secondary | 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) | Descriptive statistics will be used for assessment. A scale used to quantify performance of activities of daily living. Scores on the ADCS-ADL range from 0-78, with higher scores indicating better ADL function. | Participants with at least one predose and one postdose ADA assessment were included in this analysis. | Posted | Count of Participants | Participants | Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2 |
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| Secondary | 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) | Descriptive statistics will be used for assessment. A scale used to quantify the severity of symptoms of dementia. The CDR-SB is obtained through interviews of patients and informants, and disease severity is rated in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a 5-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment (personal care is scored on a 4-point scale without a 0.5 rating available). The CDR-SOB score is obtained by summing each of the domain box scores, with scores ranging from 0 to 18, with the higher values representing more severe impairment. | Participants with at least one predose and one postdose ADA assessment were included in this analysis. | Posted | Count of Participants | Participants | Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2 |
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| Secondary | Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE) | Descriptive statistics will be used for assessment. The Mini Mental State Examination (MMSE) is a brief clinical cognitive examination commonly used to screen for dementia and other cognitive deficits that has a total score of 0-30. Higher scores indicate better cognitive function. | Participants with at least one predose and one postdose ADA assessment were included in this analysis. | Posted | Count of Participants | Participants | Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2 |
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| Secondary | Relationship Between ADA Status and Serum Concentration of RO7105705 at Specified Timepoints | Descriptive statistics will be used for assessment. | Participants with at least one predose and one postdose ADA assessment were included in this analysis. | Posted | Count of Participants | Participants | 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. |
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| Secondary | Relationship Between ADA Status and Incidence of Anti-Drug Antibodies (ADAs) During the Study Relative to the Prevalence of ADAs at Baseline | Descriptive statistics will be used for assessment. | Participants with at least one predose and one postdose ADA assessment were included in this analysis. | Posted | Count of Participants | Participants | 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. |
|
|
Baseline up to end of study (approximately 4 years and 7 months)
The safety population included all randomized participants who received at least one dose of either semorinemab or placebo.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Semorinemab (Double Blind) | Semorinemab was administered intravenously in the double-blind treatment period | 1 | 135 | 23 | 135 | 78 | 135 |
| EG001 | Placebo | Placebo was administered intravenously in the double-blind treatment period and semorinemab was administered intravenously in the optional open-label extension. | 3 | 132 | 22 | 132 | 74 | 132 |
| EG002 | Semorinemab (OLE) | Semorinemab was administered intravenously in the optional open-label extension period. | 2 | 199 | 37 | 199 | 122 | 199 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leukocytosis | Blood and lymphatic system disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Bradycardia | Cardiac disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Stress cardiomyopathy | Cardiac disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Hernial eventration | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Inguinal hernia strangulated | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Death | General disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA 26.0 | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Cystitis | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Urosepsis | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Craniocerebral injury | Injury, poisoning and procedural complications | MedDRA 26.0 | Systematic Assessment |
| |
| Femoral neck fracture | Injury, poisoning and procedural complications | MedDRA 26.0 | Systematic Assessment |
| |
| Head injury | Injury, poisoning and procedural complications | MedDRA 26.0 | Systematic Assessment |
| |
| Hip fracture | Injury, poisoning and procedural complications | MedDRA 26.0 | Systematic Assessment |
| |
| Joint dislocation | Injury, poisoning and procedural complications | MedDRA 26.0 | Systematic Assessment |
| |
| Patella fracture | Injury, poisoning and procedural complications | MedDRA 26.0 | Systematic Assessment |
| |
| SARS-CoV-2 test positive | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Diabetic metabolic decompensation | Metabolism and nutrition disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Adenocarcinoma metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 26.0 | Systematic Assessment |
| |
| Invasive ductal breast carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 26.0 | Systematic Assessment |
| |
| Ovarian cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 26.0 | Systematic Assessment |
| |
| Renal neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 26.0 | Systematic Assessment |
| |
| Squamous cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 26.0 | Systematic Assessment |
| |
| Transitional cell carcinoma recurrent | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 26.0 | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Dysarthria | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Subarachnoid haemorrhage | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Upper motor neurone lesion | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Agitation | Psychiatric disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Hydronephrosis | Renal and urinary disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Aortic aneurysm | Vascular disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Peripheral artery thrombosis | Vascular disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Arrhythmia | Cardiac disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Sinus node dysfunction | Cardiac disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA 26.0 | Systematic Assessment |
| |
| COVID-19 pneumonia | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Aggression | Psychiatric disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Peripheral artery aneurysm | Vascular disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Intestinal obstruction | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Hypothermia | General disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Biliary fistula | Hepatobiliary disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Epididymitis | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Escherichia bacteraemia | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Brain contusion | Injury, poisoning and procedural complications | MedDRA 26.0 | Systematic Assessment |
| |
| Cervical vertebral fracture | Injury, poisoning and procedural complications | MedDRA 26.0 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 26.0 | Systematic Assessment |
| |
| Femur fracture | Injury, poisoning and procedural complications | MedDRA 26.0 | Systematic Assessment |
| |
| Rib fracture | Injury, poisoning and procedural complications | MedDRA 26.0 | Systematic Assessment |
| |
| Lung cancer metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 26.0 | Systematic Assessment |
| |
| Lung neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 26.0 | Systematic Assessment |
| |
| Cerebellar infarction | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Generalised tonic-clonic seizure | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Loss of consciousness | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Anuria | Renal and urinary disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Prostatitis | Reproductive system and breast disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Scrotal oedema | Reproductive system and breast disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA 26.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 26.0 | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 26.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Agitation | Psychiatric disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 26.0 | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
|
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Hoffmann-La Roche | 800-821-8590 | genentech@druginfo.com |
| Jul 15, 2022 |
| Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| C000710691 | (18F)GTP1 |
Not provided
Not provided
Not provided
| Lost to Follow-up |
|
| Withdrawal by Subject |
|
| Various reasons |
|
| Physician Decision |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Change from Baseline at Week 49 (includes Cohort 1 and 2) |
|
|
| Change from Baseline at Week 61 (only Cohort 2) |
|
|
| Mixed Models Analysis |
| 0.0351 |
| Least Squares Mean Difference |
| -2.75 |
| Standard Error of the Mean |
| 1.287 |
| 2-Sided |
| 95 |
| -5.31 |
| -0.20 |
| Superiority |
| Participants |
|
|
|
Placebo was administered intravenously in the double-blind treatment period and semorinemab was administered intravenously in the optional open-label extension.
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Semorinemab was administered intravenously in the optional open-label extension period. |
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