Study NCT03828747
A Study of Semorinemab in Patients With Moderate Alzheimer's Disease
Submitted Date:  July 15, 2022 (v36)
Quality Control Review Has Not Concluded

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Open or close this module Study Identification
Unique Protocol ID: GN40040
Brief Title: A Study of Semorinemab in Patients With Moderate Alzheimer's Disease
Official Title: A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study of MTAU9937A in Patients With Moderate Alzheimer's Disease
Secondary IDs:
Open or close this module Study Status
Record Verification: July 2022
Overall Status: Active, not recruiting
Study Start: January 30, 2019
Primary Completion: July 20, 2021 [Actual]
Study Completion: August 23, 2023 [Anticipated]
First Submitted: January 29, 2019
First Submitted that
Met QC Criteria:
January 31, 2019
First Posted: February 4, 2019 [Actual]
Results First Submitted: July 15, 2022
Results First Submitted that
Met QC Criteria:
Results First Posted: August 11, 2022 [Actual]
Last Update Submitted that
Met QC Criteria:
Last Update Posted: August 11, 2022 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Genentech, Inc.
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary: 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.
Detailed Description:
Open or close this module Conditions
Conditions: Alzheimer's Disease
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation: Randomized
Enrollment: 272 [Actual]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Semorinemab
Semorinemab will be administered intravenously in the double-blind treatment period, and semorinemab will be administered intravenously in the optional open-label extension period.
Drug: Semorinemab
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.
Other Names:
  • MTAU9937A
  • RO7105705
Drug: [18F]GTP1
[18F]GTP1 will be administered as a solution for intravenous (IV) use, as part of positron emission tomography (PET) imaging.
Placebo Comparator: Placebo
Placebo will be administered intravenously in the double-blind treatment period and semorinemab will be administered intravenously in the optional open-label extension.
Drug: Placebo
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.
Drug: [18F]GTP1
[18F]GTP1 will be administered as a solution for intravenous (IV) use, as part of positron emission tomography (PET) imaging.
Open or close this module Outcome Measures
[See Results Section.]
Primary Outcome Measures:
1. 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 Cohort 1, and Baseline to Week 61 for Cohort 2 ]

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.

Quality Control Review Comment provided by the National Library of Medicine:

  1. The description of the scale or categories does not include sufficient information to understand the results reported.
  2. The measure does not appear to include sufficient information to understand how outcomes are measured and reported.
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)
[ Time Frame: Baseline to Week 49 for Cohort 1, and Baseline to Week 61 for Cohort 2 ]

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.

Quality Control Review Comment provided by the National Library of Medicine:

  1. The measure does not appear to include sufficient information to understand how outcomes are measured and reported.
Secondary Outcome Measures:
1. 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 Cohort 1, and Baseline to Week 61 for Cohort 2 ]

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.

Quality Control Review Comment provided by the National Library of Medicine:

  1. The measure does not appear to include sufficient information to understand how outcomes are measured and reported.
2. 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 Cohort 1, and Baseline to Week 61 for Cohort 2 ]

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.

Quality Control Review Comment provided by the National Library of Medicine:

  1. The measure does not appear to include sufficient information to understand how outcomes are measured and reported.
3. Percentage of Participants With Adverse Events
[ Time Frame: Up to CCOD of July 20, 2021 (approximately 2.5 years) ]

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.
4. 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. ]

5. 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. ]

6. 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. ]

Descriptive statistics will be used for assessment.
7. 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 Cohort 1, and Baseline to Week 61 for Cohort 2 ]

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.

8. 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 Cohort 1, and Baseline to Week 61 for Cohort 2 ]

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.

9. 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 Cohort 1, and Baseline to Week 61 for Cohort 2 ]

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.

10. 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 Cohort 1, and Baseline to Week 61 for Cohort 2 ]

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.

11. 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. ]

Descriptive statistics will be used for assessment.
12. 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. ]

Descriptive statistics will be used for assessment.
Open or close this module Eligibility
Minimum Age: 50 Years
Maximum Age: 85 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

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
Open or close this module Contacts/Locations
Study Officials: Clinical Trials
Study Director
Hoffmann-La Roche
Locations: United States, California
Collaborative Neuroscience Network, Inc.
Garden Grove, California, United States, 92845
Pharmacology Research Institute
Los Alamitos, California, United States, 90720
Stanford University; Stanford Clinical Cancer Ctr
Palo Alto, California, United States, 94305
Pacific Research Network - PRN
San Diego, California, United States, 92103
United States, Connecticut
Molecular Neuroimaging; MRI/PET
New Haven, Connecticut, United States, 06510
KI Health Partners, LLC; New England Institute for Clinical Research
Stamford, Connecticut, United States, 06905
United States, Florida
JEM Research LLC
Atlantis, Florida, United States, 33462
Bradenton Research Center
Bradenton, Florida, United States, 34205
Brain Matters Research, Inc.
Delray Beach, Florida, United States, 33445
Neuropsychiatric Research; Center of Southwest Florida
Fort Myers, Florida, United States, 33912
Miami Jewish Health Systems
Miami, Florida, United States, 33137
Collier Neurologic Specialists
Naples, Florida, United States, 34105
Synexus Clinical Research US, Inc. - Orlando
Orlando, Florida, United States, 32806
Alzheimer's Research and Treatment Center
Wellington, Florida, United States, 33414
Premiere Research Institute
West Palm Beach, Florida, United States, 33407
United States, Illinois
Rush University Medical Center - Chicago
Chicago, Illinois, United States, 60612
Alexian Brothers Neuroscience Institute
Elk Grove Village, Illinois, United States, 60007
Southern Illinois University, School of Medicine
Springfield, Illinois, United States, 62702
United States, Massachusetts
Brigham and Womens Hospital; Center for Alzheimer Research & Treatment
Boston, Massachusetts, United States, 02115
Alzheimers Disease Center
Quincy, Massachusetts, United States, 02169
United States, Minnesota
Center for Memory and Aging
Saint Paul, Minnesota, United States, 55130
United States, New Jersey
Advanced Memory Research Institute of NJ
Toms River, New Jersey, United States, 08755
United States, New York
Empire Neurology PC; MS Center of Northeastern NY
Latham, New York, United States, 12110
University of Rochester; AD-CARE
Rochester, New York, United States, 14642
United States, Oregon
Summit Research Network Inc.
Portland, Oregon, United States, 97210
United States, Pennsylvania
Abington Neurological Associates
Abington, Pennsylvania, United States, 19001
United States, Rhode Island
Rhode Island Mood & Memory Research Institute
East Providence, Rhode Island, United States, 02914
Butler Hospital; Movement Disorders Program
Providence, Rhode Island, United States, 02906
United States, Tennessee
Neurology Clinic PC
Cordova, Tennessee, United States, 38018
New Orleans Center for Clinical Research
Knoxville, Tennessee, United States, 37920
United States, Vermont
The Memory Clinic
Bennington, Vermont, United States, 05201
France
Chu Toulouse
Bron, France, 69500
CHU de la Timone - Hopital d Adultes; Service de Neurologie
Marseille, France, 13005
Groupe Hospitalier Pitie-Salpetriere
Paris, France, 75651
CHU Rennes - Hopital Pontchaillou
Rennes cedex 09, France, 35033
Hopital des Charpennes
Villeurbanne, France, 69100
Poland
Podlaskie Centrum Psychogeriatrii
Białystok, Poland, 15-756
Novo-Med Zielinski i wspolnicy Sp. j.
Katowice, Poland, 40-650
NZOZ NEURO-KARD Ilkowski i Partnerzy Sp. Partn. Lek
Poznań, Poland, 61-853
Osrodek Badan Klinicznych Euromedis
Szczecin, Poland, 70-111
Centrum Medyczne NeuroProtect
Warszawa, Poland, 01-684
Centrum Medyczne AMED
Warszawa, Poland, 03-291
NZOZ WCA
Wrocław, Poland, 53-659
Spain
Fundacio ACE
Barcelona, Spain, 08028
Hospital Clinic I Provincial
Barcelona, Spain, 08036
Hospital de la Santa Creu i Sant Pau; Servicio de Neurologia
Barcelona, Spain, 08041
Hospital Universitario Doctor Peset
Valencia, Spain, 46017
Hospital Universitari i Politecnic La Fe
Valencia, Spain, 46026
Spain, Barcelona
Hospital Mutua de Terrassa
Terrassa, Barcelona, Spain, 08221
Open or close this module IPDSharing
Plan to Share IPD: Yes
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)
Supporting Information:
Time Frame:
Access Criteria:
URL:
Open or close this module References
Citations:
Links:
Available IPD/Information:
Open or close this module Document Section
Study Protocol and Statistical Analysis Plan
Document Date: December 14, 2021
Uploaded: 07/15/2022 11:36
File Name: Prot_SAP_000.pdf
Study Results
Open or close this module Participant Flow
Recruitment Details The study was conducted at 49 centers in 4 countries.
Pre-assignment Details A total of 272 participants were enrolled at 49 centers. 5 participants did not receive blinded treatment. These 267 participants represented the Safety Analysis population and data for this population is presented here.
 
Arm/Group Title Semorinemab Placebo
Arm/Group Description Semorinemab will be administered intravenously in the double-blind treatment period and will be administered intravenously in the optional open-label extension period. Placebo was administered intravenously in the double-blind treatment period and semorinemab will be administered intravenously in the optional open-label extension.

Quality Control Review Comment provided by the National Library of Medicine:

  1. Information here appears inconsistent with information in other parts of the record.
Period Title: Double-Blind Treatment Period
Started 135 132
Completed 104 96
Not Completed 31 36
Reason Not Completed
Adverse Event 6 6
Death 1 2
Lost to Follow-up 0 1
Withdrawal by Subject 19 21
Physician Decision 0 3
Various reasons 5 3
Period Title: Open-Label Extension
Started 104 95
Completed 0 0
Not Completed 104 95
Reason Not Completed
Continuing on Study 77 72
Adverse Event 3 4
Death 0 2
Lost to Follow-up 4 0
Withdrawal by Subject 19 16
Various reasons 1 1
Open or close this module Baseline Characteristics
Arm/Group TitleSemorinemabPlaceboTotal
Arm/Group DescriptionSemorinemab will be administered intravenously in the double-blind treatment period and will be administered intravenously in the optional open-label extension period.Placebo was administered intravenously in the double-blind treatment period and semorinemab will be administered intravenously in the optional open-label extension.Total of all reporting groups
Overall Number of Baseline Participants 135 132 267
Baseline Analysis Population Description [Not Specified]
Age, Continuous
Mean (Standard Deviation)
Unit of measure: Years
Number Analyzed135 Participants132 Participants267 Participants
71.6(8.2)73.1(8.0)72.3(8.1)
Sex: Female, Male
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed135 Participants132 Participants267 Participants
Female
93
68.89%
80
60.61%
173
64.79%
Male
42
31.11%
52
39.39%
94
35.21%
Ethnicity (NIH/OMB)
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed135 Participants132 Participants267 Participants
Hispanic or Latino
4
2.96%
3
2.27%
7
2.62%
Not Hispanic or Latino
116
85.93%
111
84.09%
227
85.02%
Unknown or Not Reported
15
11.11%
18
13.64%
33
12.36%
Race (NIH/OMB)
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed135 Participants132 Participants267 Participants
American Indian or Alaska Native
0
0%
0
0%
0
0%
Asian
1
0.74%
0
0%
1
0.37%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
Black or African American
4
2.96%
5
3.79%
9
3.37%
White
121
89.63%
115
87.12%
236
88.39%
More than one race
0
0%
0
0%
0
0%
Unknown or Not Reported
9
6.67%
12
9.09%
21
7.87%
Open or close this module Outcome Measures
1. Primary Outcome:
Title 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)
Description 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.
Time Frame Baseline to Week 49 for Cohort 1, and Baseline to Week 61 for Cohort 2

Quality Control Review Comment provided by the National Library of Medicine:

  1. The description of the scale or categories does not include sufficient information to understand the results reported.
  2. The measure does not appear to include sufficient information to understand how outcomes are measured and reported.
Outcome Measure Data
Analysis Population Description
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.
 
Arm/Group TitleSemorinemabPlacebo
Arm/Group DescriptionSemorinemab will be administered intravenously in the double-blind treatment period and will be administered intravenously in the optional open-label extension period.Placebo was administered intravenously in the double-blind treatment period and semorinemab will be administered intravenously in the optional open-label extension.
Overall Number of Participants Analyzed123 115
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
Baseline
23.93(0.533) 24.09(0.589)
Week 49
3.96(0.658) 6.85(0.643)
Week 61
5.71(0.907) 8.47(0.965)
Statistical Analysis 1
Statistical Analysis OverviewComparison Group SelectionSemorinemab, Placebo
CommentsWeek 49
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0008
Comments[Not specified]
MethodMixed Models Analysis
Comments[Not specified]
Method of EstimationEstimation ParameterLeast Squares Mean Difference
Estimated Value-2.89
Confidence Interval(2-sided) 95%
-4.56 to -1.21
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.849
Estimation Comments[Not specified]
Statistical Analysis 2
Statistical Analysis OverviewComparison Group SelectionSemorinemab, Placebo
CommentsWeek 61
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0351
Comments[Not specified]
MethodMixed Models Analysis
Comments[Not specified]
Method of EstimationEstimation ParameterLeast Squares Mean Difference
Estimated Value-2.75
Confidence Interval(2-sided) 95%
-5.31 to -0.20
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.287
Estimation Comments[Not specified]
2. Primary Outcome:
Title 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)
Description 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.
Time Frame Baseline to Week 49 for Cohort 1, and Baseline to Week 61 for Cohort 2

Quality Control Review Comment provided by the National Library of Medicine:

  1. The measure does not appear to include sufficient information to understand how outcomes are measured and reported.
Outcome Measure Data
Analysis Population Description
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.
 
Arm/Group TitleSemorinemabPlacebo
Arm/Group DescriptionSemorinemab will be administered intravenously in the double-blind treatment period and will be administered intravenously in the optional open-label extension period.Placebo was administered intravenously in the double-blind treatment period and semorinemab will be administered intravenously in the optional open-label extension.
Overall Number of Participants Analyzed123 115
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
Baseline
62.03(0.764) 59.74(0.842)
Week 49
-7.63(1.002) -6.80(0.974)
Week 61
-9.29(1.343) -7.57(1.462)
Statistical Analysis 1
Statistical Analysis OverviewComparison Group SelectionSemorinemab, Placebo
CommentsWeek 49
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.5207
Comments[Not specified]
MethodMixed Models Analysis
Comments[Not specified]
Method of EstimationEstimation ParameterLeast Squares Mean Difference
Estimated Value-0.83
Confidence Interval(2-sided) 95%
-3.39 to 1.72
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.295
Estimation Comments[Not specified]
Statistical Analysis 2
Statistical Analysis OverviewComparison Group SelectionSemorinemab, Placebo
CommentsWeek 61
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.3704
Comments[Not specified]
MethodMixed Models Analysis
Comments[Not specified]
Method of EstimationEstimation ParameterLeast Squares Mean Difference
Estimated Value-1.72
Confidence Interval(2-sided) 95%
-5.50 to 2.07
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.911
Estimation Comments[Not specified]
3. Secondary Outcome:
Title Change From Baseline to Last Visit of Double-Blind Treatment Period on the Clinical Dementia Rating-Sum of Boxes (CDR-SB)
Description 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.
Time Frame Baseline to Week 49 for Cohort 1, and Baseline to Week 61 for Cohort 2

Quality Control Review Comment provided by the National Library of Medicine:

  1. The measure does not appear to include sufficient information to understand how outcomes are measured and reported.
Outcome Measure Data
Analysis Population Description
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.
 
Arm/Group TitleSemorinemabPlacebo
Arm/Group DescriptionSemorinemab will be administered intravenously in the double-blind treatment period and will be administered intravenously in the optional open-label extension period.Placebo was administered intravenously in the double-blind treatment period and semorinemab will be administered intravenously in the optional open-label extension.
Overall Number of Participants Analyzed123 115
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
Baseline
6.23(0.156) 6.51(0.182)
Week 49
1.80(0.217) 1.54(0.214)
Week 61
2.45(0.367) 2.28(0.393)
Statistical Analysis 1
Statistical Analysis OverviewComparison Group SelectionSemorinemab, Placebo
CommentsWeek 49
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.3501
Comments[Not specified]
MethodMixed Models Analysis
Comments[Not specified]
Method of EstimationEstimation ParameterLeast Squares Mean Difference
Estimated Value0.26
Confidence Interval(2-sided) 95%
-0.29 to 0.82
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.282
Estimation Comments[Not specified]
Statistical Analysis 2
Statistical Analysis OverviewComparison Group SelectionSemorinemab, Placebo
CommentsWeek 61
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.7431
Comments[Not specified]
MethodMixed Models Analysis
Comments[Not specified]
Method of EstimationEstimation ParameterLeast Squares Mean Difference
Estimated Value0.17
Confidence Interval(2-sided) 95%
-0.87 to 1.22
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.525
Estimation Comments[Not specified]
4. Secondary Outcome:
Title Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE)
Description 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.
Time Frame Baseline to Week 49 for Cohort 1, and Baseline to Week 61 for Cohort 2

Quality Control Review Comment provided by the National Library of Medicine:

  1. The measure does not appear to include sufficient information to understand how outcomes are measured and reported.
Outcome Measure Data
Analysis Population Description
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.
 
Arm/Group TitleSemorinemabPlacebo
Arm/Group DescriptionSemorinemab will be administered intravenously in the double-blind treatment period and will be administered intravenously in the optional open-label extension period.Placebo was administered intravenously in the double-blind treatment period and semorinemab will be administered intravenously in the optional open-label extension.
Overall Number of Participants Analyzed123 115
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
Baseline
18.38(0.182) 18.15(0.197)
Week 49
-2.86(0.330) -3.12(0.325)
Week 61
-3.14(0.429) -4.22(0.466)
Statistical Analysis 1
Statistical Analysis OverviewComparison Group SelectionSemorinemab, Placebo
CommentsWeek 49
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.5366
Comments[Not specified]
MethodMixed Models Analysis
Comments[Not specified]
Method of EstimationEstimation ParameterLeast Squares Mean Difference
Estimated Value0.27
Confidence Interval(2-sided) 95%
-0.58 to 1.11
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.429
Estimation Comments[Not specified]
Statistical Analysis 2
Statistical Analysis OverviewComparison Group SelectionSemorinemab, Placebo
CommentsWeek 61
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0851
Comments[Not specified]
MethodMixed Models Analysis
Comments[Not specified]
Method of EstimationEstimation ParameterLeast Squares Mean Difference
Estimated Value1.08
Confidence Interval(2-sided) 95%
-0.15 to 2.30
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.618
Estimation Comments[Not specified]
5. Secondary Outcome:
Title Percentage of Participants With Adverse Events
Description 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.
Time Frame Up to CCOD of July 20, 2021 (approximately 2.5 years)
Outcome Measure Data
Analysis Population Description
The safety population included all randomized participants who received at least one dose of either semorinemab or placebo.
 
Arm/Group TitleSemorinemabPlacebo
Arm/Group DescriptionSemorinemab will be administered intravenously in the double-blind treatment period and will be administered intravenously in the optional open-label extension period.Placebo was administered intravenously in the double-blind treatment period and semorinemab will be administered intravenously in the optional open-label extension.
Overall Number of Participants Analyzed135 132
Measure Type: Count of Participants
Unit of Measure: Participants
113
83.7%
107
81.1%
6. Secondary Outcome:
Title Serum Concentration of RO7105705 at Specified Timepoints
Description
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.
Anticipated Reporting Date August 2024
Outcome Measure Data Not Reported
7. Secondary Outcome:
Title Incidence of Anti-drug Antibodies (ADAs) During the Study Relative to the Prevalence of ADAs at Baseline
Description
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.
Anticipated Reporting Date August 2024
Outcome Measure Data Not Reported
8. Secondary Outcome:
Title Relationship Between ADA Status and Percentage of Participants With Adverse Events
Description Descriptive statistics will be used for assessment.
Time Frame Up to 57 weeks for Cohort 1, and up to 69 weeks for Cohort 2.
Anticipated Reporting Date August 2024
Outcome Measure Data Not Reported
9. Secondary Outcome:
Title 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)
Description

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.

Time Frame Baseline to Week 49 for Cohort 1, and Baseline to Week 61 for Cohort 2
Anticipated Reporting Date August 2024
Outcome Measure Data Not Reported
10. Secondary Outcome:
Title 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)
Description

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.

Time Frame Baseline to Week 49 for Cohort 1, and Baseline to Week 61 for Cohort 2
Anticipated Reporting Date August 2024
Outcome Measure Data Not Reported
11. Secondary Outcome:
Title 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)
Description

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.

Time Frame Baseline to Week 49 for Cohort 1, and Baseline to Week 61 for Cohort 2
Anticipated Reporting Date August 2024
Outcome Measure Data Not Reported
12. Secondary Outcome:
Title Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE)
Description

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.

Time Frame Baseline to Week 49 for Cohort 1, and Baseline to Week 61 for Cohort 2
Anticipated Reporting Date August 2024
Outcome Measure Data Not Reported
13. Secondary Outcome:
Title Relationship Between ADA Status and Serum Concentration of RO7105705 at Specified Timepoints
Description Descriptive statistics will be used for assessment.
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.
Anticipated Reporting Date August 2024
Outcome Measure Data Not Reported
14. Secondary Outcome:
Title Relationship Between ADA Status and Incidence of Anti-Drug Antibodies (ADAs) During the Study Relative to the Prevalence of ADAs at Baseline
Description Descriptive statistics will be used for assessment.
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.
Anticipated Reporting Date August 2024
Outcome Measure Data Not Reported
Open or close this module Adverse Events
 
Time Frame Up to CCOD of July 20, 2021 (approximately 2.5 years)
Adverse Event Reporting Description The adverse events presented refer to those that occurred in the double-blind period only.

Quality Control Review Comment provided by the National Library of Medicine:

  1. Information in other parts of the record suggests that adverse events were collected that are not reported here.
 
Arm/Group Title Semorinemab Placebo
Arm/Group Description Semorinemab will be administered intravenously in the double-blind treatment period and will be administered intravenously in the optional open-label extension period. Placebo was administered intravenously in the double-blind treatment period and semorinemab will be administered intravenously in the optional open-label extension.
All-Cause Mortality
  SemorinemabPlacebo
 Affected / At Risk (%)# Events Affected / At Risk (%)# Events
Total 1 / 135 (0.74%)2 / 132 (1.52%)

Quality Control Review Comment provided by the National Library of Medicine:

  1. Information in other parts of the record suggests that adverse events were collected that are not reported here.
Serious Adverse Events
  SemorinemabPlacebo
 Affected / At Risk (%)# Events Affected / At Risk (%)# Events
Total 22 / 135 (16.3%)22 / 132 (16.67%)
Blood and lymphatic system disorders
Leukocytosis † A 1 / 135 (0.74%)10 / 132 (0%)0
Cardiac disorders
Atrial fibrillation † A 1 / 135 (0.74%)10 / 132 (0%)0
Bradycardia † A 1 / 135 (0.74%)10 / 132 (0%)0
Cardiac failure † A 0 / 135 (0%)01 / 132 (0.76%)1
Stress cardiomyopathy † A 1 / 135 (0.74%)10 / 132 (0%)0
Gastrointestinal disorders
Abdominal pain † A 0 / 135 (0%)02 / 132 (1.52%)2
Colitis † A 1 / 135 (0.74%)10 / 132 (0%)0
Hernial eventration † A 0 / 135 (0%)01 / 132 (0.76%)1
Inguinal hernia strangulated † A 1 / 135 (0.74%)10 / 132 (0%)0
General disorders
Death † A 1 / 135 (0.74%)11 / 132 (0.76%)1
Non-cardiac chest pain † A 0 / 135 (0%)01 / 132 (0.76%)1
Hepatobiliary disorders
Cholelithiasis † A 0 / 135 (0%)01 / 132 (0.76%)1
Infections and infestations
COVID-19 † A 1 / 135 (0.74%)12 / 132 (1.52%)2
Cystitis † A 1 / 135 (0.74%)10 / 132 (0%)0
Gastroenteritis † A 1 / 135 (0.74%)10 / 132 (0%)0
Pneumonia † A 0 / 135 (0%)02 / 132 (1.52%)2
Urinary tract infection † A 1 / 135 (0.74%)10 / 132 (0%)0
Urosepsis † A 0 / 135 (0%)01 / 132 (0.76%)1
Injury, poisoning and procedural complications
Craniocerebral injury † A 1 / 135 (0.74%)10 / 132 (0%)0
Femoral neck fracture † A 1 / 135 (0.74%)10 / 132 (0%)0
Head injury † A 0 / 135 (0%)01 / 132 (0.76%)1
Hip fracture † A 0 / 135 (0%)02 / 132 (1.52%)2
Joint dislocation † A 1 / 135 (0.74%)10 / 132 (0%)0
Patella fracture † A 1 / 135 (0.74%)10 / 132 (0%)0
Investigations
SARS-CoV-2 test positive † A 1 / 135 (0.74%)10 / 132 (0%)0
Metabolism and nutrition disorders
Dehydration † A 1 / 135 (0.74%)11 / 132 (0.76%)1
Diabetic metabolic decompensation † A 1 / 135 (0.74%)10 / 132 (0%)0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma metastatic † A 1 / 135 (0.74%)10 / 132 (0%)0
Invasive ductal breast carcinoma † A 1 / 135 (0.74%)10 / 132 (0%)0
Ovarian cancer † A 1 / 135 (0.74%)10 / 132 (0%)0
Renal neoplasm † A 0 / 135 (0%)01 / 132 (0.76%)1
Squamous cell carcinoma † A 1 / 135 (0.74%)10 / 132 (0%)0
Transitional cell carcinoma recurrent † A 1 / 135 (0.74%)10 / 132 (0%)0
Nervous system disorders
Cerebrovascular accident † A 0 / 135 (0%)01 / 132 (0.76%)1
Dysarthria † A 1 / 135 (0.74%)10 / 132 (0%)0
Seizure † A 1 / 135 (0.74%)11 / 132 (0.76%)1
Subarachnoid haemorrhage † A 1 / 135 (0.74%)10 / 132 (0%)0
Syncope † A 1 / 135 (0.74%)11 / 132 (0.76%)1
Upper motor neurone lesion † A 1 / 135 (0.74%)10 / 132 (0%)0
Psychiatric disorders
Agitation † A 0 / 135 (0%)03 / 132 (2.27%)3
Renal and urinary disorders
Hydronephrosis † A 0 / 135 (0%)01 / 132 (0.76%)1
Nephrolithiasis † A 0 / 135 (0%)01 / 132 (0.76%)1
Renal failure † A 1 / 135 (0.74%)10 / 132 (0%)0
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism † A 0 / 135 (0%)01 / 132 (0.76%)1
Vascular disorders
Aortic aneurysm † A 0 / 135 (0%)01 / 132 (0.76%)1
Peripheral artery thrombosis † A 1 / 135 (0.74%)10 / 132 (0%)0
Indicates events were collected by systematic assessment.
ATerm from vocabulary, MedDRA 24.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
  SemorinemabPlacebo
 Affected / At Risk (%)# Events Affected / At Risk (%)# Events
Total 77 / 135 (57.04%)71 / 132 (53.79%)
Gastrointestinal disorders
Diarrhoea † A 7 / 135 (5.19%)75 / 132 (3.79%)6
Infections and infestations
Nasopharyngitis † A 9 / 135 (6.67%)103 / 132 (2.27%)3
Urinary tract infection † A 10 / 135 (7.41%)1416 / 132 (12.12%)19
Injury, poisoning and procedural complications
Fall † A 14 / 135 (10.37%)1919 / 132 (14.39%)28
Infusion related reaction † A 14 / 135 (10.37%)305 / 132 (3.79%)9
Musculoskeletal and connective tissue disorders
Arthralgia † A 7 / 135 (5.19%)74 / 132 (3.03%)4
Nervous system disorders
Dizziness † A 8 / 135 (5.93%)89 / 132 (6.82%)11
Headache † A 11 / 135 (8.15%)149 / 132 (6.82%)10
Psychiatric disorders
Agitation † A 8 / 135 (5.93%)85 / 132 (3.79%)5
Anxiety † A 9 / 135 (6.67%)1112 / 132 (9.09%)12
Depression † A 10 / 135 (7.41%)106 / 132 (4.55%)6
Insomnia † A 7 / 135 (5.19%)72 / 132 (1.52%)2
Vascular disorders
Hypertension † A 8 / 135 (5.93%)105 / 132 (3.79%)5
Indicates events were collected by systematic assessment.
ATerm from vocabulary, MedDRA 24.1
Open or close this module Limitations and Caveats
[Not specified]
Open or close this module More Information
Certain Agreements:
Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between the Principal Investigator and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.
Results Point of Contact:
Name/Official Title:
Medical Communications
Organization:
Hoffmann-La Roche
Phone:
800-821-8590
Email:
genentech@druginfo.com

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