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A Study to Evaluate the Efficacy and Safety of Semorinemab in Patients With Prodromal to Mild Alzheimer's Disease

Sponsor
Genentech, Inc. (Industry)
Overall Status
Terminated
CT.gov ID
NCT03289143
Collaborator
(none)
457
Enrollment
133
Locations
4
Arms
39.4
Actual Duration (Months)
3.4
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This was a phase II, randomized, placebo-controlled, double-blind study to evaluate the efficacy and safety of Semorinemab in participants with prodromal to mild Alzheimer's disease. An optional 96-week open-label extension period was available to participants who completed the double-blind treatment period and who, in the judgment of the investigator, would potentially benefit from open-label Semorinemab treatment.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
457 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:
Additional blinded personnel will include study site personnel who will evaluate participant status, contract research organization (CRO) personnel who will review case report forms (CRFs), and other sponsor agents (with the exception of the interactive voice or web-based response system [IxRS] vendor).
Primary Purpose:
Treatment
Official Title:
A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study of MTAU9937A in Patients With Prodromal to Mild Alzheimer's Disease
Actual Study Start Date :
Oct 4, 2017
Actual Primary Completion Date :
Jan 15, 2021
Actual Study Completion Date :
Jan 15, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Dose 1 Semorinemab

Drug: Semorinemab
Participants will receive Semorinemab intravenously (IV).
Other Names:
  • RG6100
  • 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.
    Other Names:
  • RO6880276

    		•
    Experimental: Dose 2 Semorinemab

    Drug: Semorinemab
    Participants will receive Semorinemab intravenously (IV).
    Other Names:
  • RG6100
  • 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.
    Other Names:
  • RO6880276

    		•
    Experimental: Dose 3 Semorinemab

    Drug: Semorinemab
    Participants will receive Semorinemab intravenously (IV).
    Other Names:
  • RG6100
  • 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.
    Other Names:
  • RO6880276

    		•
    Placebo Comparator: Placebo

    Drug: Placebo
    Matching placebo doses of Semorinemab given intravenously (IV).

    Drug: [18F]GTP1
    [18F]GTP1 will be administered as a solution for intravenous (IV) use, as part of positron emission tomography (PET) imaging.
    Other Names:
  • RO6880276

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline on the CDR-SB [Baseline and 73 Weeks]

      The Clinical Dementia Rating-Sum of Boxes (CDR-SB) rates impairment in 6 categories (memory, orientation, judgement and problem solving, community affairs, home and hobbies and personal care) on a 5-point scale in which no impairment = 0, questionable impairment = 0.5 and mild, moderate and severe impairment = 1, 2 and 3 respectively. The score range is from 0 to 18 with a high score indicating a high disease severity. The difference in mean change from Baseline to Week 73 between Semorinemab doses and Placebo treated participants was estimated. The difference in mean change from Baseline to Week 73 between Semorinemab doses and Placebo treated participants was estimated.

    2. Percentage of Participants With Adverse Events [Up to the data cutoff date 15 January 2021 (up to approximately 39 months)]

      Percentage of participants with at least one adverse event

    3. Change From Baseline on the C-SSRS [Baseline to data cutoff date 15 January 2021 (up to approximately 39 months)]

      Categories are as defined in the Classification Algorithm for Suicide Assessment (CASA) based on the Columbia Suicide Severity Rating Scale (C-SSRS) questionnaire. SI1: Passive category is "Wish to be dead", SI2: Active-Nonspecific (no method, intent or plan), SI3: Active-Method, but no intent or Plan, SI4: Active-Method and intent, but no plan in C-SSRS. The worst post-baseline suicidal ideation is the highest across post-baseline visits, with highest as SI5 and lowest as SI1. Percentages are based on the total number of subjects in a treatment group. Baseline is the last observation prior to initiation of study drug.

    4. Other Abnormal MRI Findings [Baseline, Week 9, Week 49, Week 73, Study Treatment Discontinuation, and Week 89]

      Other abnormal MRI findings by visit. For the Double Blind Period, baseline is defined as last results prior to initiation of study drug. For the Open Label Extension Period, baseline is defined as last results prior to entering the open label period.

    Secondary Outcome Measures

    1. Change From Baseline on the Repeatable Battery for Assessment of Neuropsychological Status (RBANS) [Baseline and 73 weeks]

      The RBANS is a validated neuropsychological assessment has been shown to be a useful tool in both clinical and research settings. The RBANS consists of ten subtests that are combined to provide five indices, one for each of the five domains tested (immediate memory, visuospatial/constructional, language, attention, and delayed memory). Scores range from 40 to 160 and a higher score indicates better cognitive functioning. A decrease in the outcome measure from baseline corresponds to disease worsening. The difference in mean change from Baseline to Week 73 between Semorinemab doses and Placebo treated participants was estimated.

    2. Change From Baseline on the Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog-13) Subscale Score [Baseline and 73 weeks]

      The ADAS-Cog-13 assesses multiple cognitive domains including memory, comprehension, praxis, orientation, and spontaneous speech. Most of these are assessed by tests although some are rated by the clinician on a 5-point scale. The ADAS-Cog-13 is the ADAS-Cog-11 with 2 further items: delayed word recall and total digit cancellation. The score range for ADAS-Cog-13 is from 0 to 85 with high scores representing severe dysfunction. The difference in mean change from Baseline to Week 73 between Semorinemab doses and Placebo treated participants was estimated.

    3. Change From Baseline on the Amsterdam Instrumental Activity of Daily Living (iADL) Questionnaire [Baseline and 73 weeks]

      The Amsterdam iADL questionnaire is an informant-based instrument for measuring iADL problems in participants with dementia. This instrument consists of 70 items, scored on a 5-point scale, that uses item response theory for scoring. Items presented to the informant are tailored to responses to earlier items; thus each administration of the Amsterdam iADL may consist of less than the total of 70 items. The resulting score ranges from 20 to 80 with lower scores indicating poorer performance. A decrease in the outcome measure from baseline corresponds to disease worsening. The difference in mean change from Baseline to Week 73 between Semorinemab doses and Placebo treated participants was estimated.

    4. Change From Baseline on the Alzheimer's Disease Cooperative Study Group-Activities of Daily Living Inventory [Baseline and 73 weeks]

      The ADCS-ADL (Alzheimer's Disease Cooperative Study-Activities of Daily Living) is the scale most widely used to assess functional outcomes in participants with AD. The ADCS-ADL covers both basic ADL (e.g., eating and toileting) and more complex 'instrumental' ADL or iADL (e.g., using the telephone, managing finances and preparing a meal). The ADCS-ADL consists of 23 questions with a score range of 0 to 78 where a higher score represents better function. The difference in mean change from Baseline to Week 73 between Semorinemab doses and Placebo treated participants was estimated.

    5. Serum Concentrations of Semorinemab at Specified Timepoints [Up to 109 weeks]

      Serum concentrations of Semorinemab at specified timepoints.

    6. Presence of Anti-drug Antibodies During the Study Relative to Their Presence at Baseline [Up to 109 weeks]

      Presence of anti-drug antibodies during the study relative to their presence at baseline.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    50 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    Inclusion criteria

    • Age between 50 and 80 years

    • National Institute on Aging/Alzheimer's Association core clinical criteria for probable Alzheimer's disease (AD) dementia or mild cognitive impairment (prodromal AD)

    • Evidence of the AD pathological process, by a positive amyloid assessment either on cerebrospinal fluid Aβ1-42 OR amyloid positron emission tomography (PET) scan. Historical amyloid PET scans may be accepted in some cases

    • Mild AD symptomatology, as defined by a screening Mini-Mental State Examination score of >= 20 points and Clinical Dementia Rating (CDR) -Global Score of 0.5 or 1

    • Abnormal memory function at screening

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

    Exclusion criteria

    • Pregnant or breastfeeding

    • Inability to tolerate magnetic resonance imaging (MRI) procedures or contraindication to MRI

    • Contraindications to both PET imaging and lumbar dural puncture (must be able to undergo at least one of these procedures to be eligible)

    • Residence in a skilled nursing facility

    • Any serious medical condition or abnormality in clinical laboratory tests that remains abnormal on retest and, in the investigator's judgment, precludes the patient's safe participation in and completion of the study, or bias the assessment of the clinical or mental status of the participant to a significant degree

    • Any evidence of a condition other than AD that may affect cognition

    • Alcohol or substance abuse within the past 2 years

    • Use of any experimental therapy within 90 days or 5 half-lives prior to screening, whichever is greater and any passive immunotherapy (immunoglobulin) against tau, except use of RO7105705 in Genentech Study GN39058, as long as the last dose was at least 90 days prior to screening

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

    • Any previous treatment with medications specifically intended to treat Parkinsonian symptoms or any other neurodegenerative disorder within 1 year of screening

    • Systemic immunosuppressive therapy within 12 months of screening through the entire study period

    • Typical antipsychotic or neuroleptic medication within 6 months of screening

    • Daily treatment with any of the following classes of medication, except for intermittent short-term use, which is permitted except within 2 days or 5 half-lives (whichever is longer) prior to any COA: atypical antipsychotics, opiates or opioids, benzodiazepines, barbiturates, hypnotics, or any medication with clinically significant centrally-acting antihistamine or anticholinergic activity

    • Stimulant medications, unless the dose has been stable within the 6 months prior to screening and is expected to be stable throughout the study

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama at Birmingham Birmingham Alabama United States 35249
    2 California Clinical Trials Glendale California United States 91206
    3 University of California Irvine Irvine California United States 92697
    4 Pharmacology Research Inst Newport Beach California United States 92660
    5 Stanford Neuroscience Health Center (SNHC) Palo Alto California United States 94304
    6 Pacific Research Network - PRN San Diego California United States 92103
    7 Neurological Research Inst Santa Monica California United States 90404
    8 Collaborative Neuroscience Network Inc. Torrance California United States 90502
    9 Invicro, a Konica Minolta company New Haven Connecticut United States 06510
    10 Yale University New Haven Connecticut United States 06510
    11 KI Health Partners, LLC; New England Institute for Clinical Research Stamford Connecticut United States 06905
    12 Georgetown University Hospital Washington District of Columbia United States 20057
    13 JEM Research LLC Atlantis Florida United States 33462
    14 Bradenton Research Center Bradenton Florida United States 34205
    15 Brain Matters Research, Inc. Delray Beach Florida United States 33445
    16 Neuropsychiatric Research; Center of Southwest Florida Fort Myers Florida United States 33912
    17 Miami Jewish Health Systems Miami Florida United States 33137
    18 Collier Neurologic Specialists Naples Florida United States 34105
    19 Compass Research East, LLC Orlando Florida United States 32806
    20 Stedman Clinical Trials, LLC Tampa Florida United States 33613
    21 Alzheimer's Research and Treatment Center Wellington Florida United States 33414
    22 Premiere Research Institute West Palm Beach Florida United States 33407
    23 Emory University; Global Health Atlanta Georgia United States 30322
    24 Rush Alzheimer's Disease Cntr. Chicago Illinois United States 60612
    25 Alexian Brothers Neuroscience Institute Elk Grove Village Illinois United States 60007
    26 Southern Illinois University, School of Medicine Springfield Illinois United States 62702
    27 Eastern Maine Medical Center Bangor Maine United States 04401
    28 Brigham & Women's Hosp; TIMI Study Grp Boston Massachusetts United States 02115
    29 Alzheimers Disease Center Quincy Massachusetts United States 02169
    30 Health Partners Institute for Education and Research Saint Paul Minnesota United States 55130
    31 NeuroCognitive Institute Mount Arlington New Jersey United States 07856
    32 Advanced Memory Research Institute of NJ Toms River New Jersey United States 08755
    33 Albany Medical College; Neurology Albany New York United States 12208
    34 Empire Neurology PC; MS Center of Northeastern NY Latham New York United States 12110
    35 Columbia Univ Medical Center New York New York United States 10032
    36 University of Rochester; AD-CARE Rochester New York United States 14642
    37 Summit Research Network Inc. Portland Oregon United States 97210
    38 Abington Neurological Associates Abington Pennsylvania United States 19001
    39 Rhode Island Mood & Memory Research Institute East Providence Rhode Island United States 02914
    40 Butler Hospital Providence Rhode Island United States 02906
    41 Neurology Clinic PC Cordova Tennessee United States 38018
    42 New Orleans Center For Clinical Research Knoxville Tennessee United States 37920
    43 Clinical Neuroscience Research Associates, Inc. Bennington Vermont United States 05201
    44 St Vincents Medical Centre Darlinghurst New South Wales Australia 2010
    45 Southern Neurology Kogarah New South Wales Australia 2217
    46 Queensland University of Technology Mermaid Waters Queensland Australia 4218
    47 Eastern Clinical Research Unit; Pharmacy Box Hill Victoria Australia 3128
    48 HammondCare Aged Psychiatry Clinical Trials Malvern Victoria Australia 3144
    49 The Alfred Hospital, Melbourne; Thrombosis and Haemostasis Unit Melbourne Victoria Australia 3004
    50 Neuro Trials Victoria Noble Park Victoria Australia 3174
    51 Royal Melbourne Hospital Parkville Victoria Australia 3050
    52 UZ Brussel Brussel Belgium 1090
    53 AZ Groeninge Kortrijk Belgium 8500
    54 UZ Leuven Leuven Belgium 3000
    55 AZ Delta Campus Westlaan Roeselare Belgium 8800
    56 JBN Medical Diagnostic Services; Clinical Trials Division Burlington Ontario Canada L7M 1K9
    57 Parkwood Institute, Mental Health Care Building London Ontario Canada N6C 0A7
    58 Elisabeth Bruyere Hospital Ottawa Ontario Canada K1N 5C8
    59 Toronto Memory Program Toronto Ontario Canada M3B 2S7
    60 Centre for Memory and Aging Toronto Ontario Canada M4G 3E8
    61 Toronto Sunnybrook Hospital Toronto Ontario Canada M4N 3M5
    62 Toronto Western Hospital Toronto Ontario Canada M5T 2S8
    63 Recherches Neuro-Hippocame Gatineau Quebec Canada J8T 8J1
    64 Center For Clinical and Basic Research (Ccbr); Site Management Organisation Aalborg Denmark 9000
    65 CCBR - Vejle - DK Vejle Denmark 7100
    66 Groupe Hospitalier Pellegrin; Service de Neurologie - 3ème étage Bordeaux France 33076
    67 Hopital Neurologique Pierre Wertheimer Bron France 69500
    68 Hopital Roger Salengro Lille France 59037
    69 CHU de la Timone - Hopital d Adultes; Service de Neurologie Marseille France 13005
    70 Hopital Gui de Chauliac; Neurologie Montpellier France 34295
    71 Hopital Fernand Widal Centre Paris France 75010
    72 Groupe Hospitalier Pitie-Salpetriere Paris France 75651
    73 CHU Rennes Rennes France 35033
    74 CHU Hautepierre; ACTR Association Recherche Clinique Rhumatologie Strasbourg France 67000
    75 CHU Strasbourg - Hôpital Hautepierre Strasbourg France 67098
    76 Hopital de La Grave Toulouse France 31059
    77 Hopital des Charpennes Villeurbanne France 69100
    78 Klinikum Bayreuth; Krankenhaus Hohe Warte Bayreuth Germany 95445
    79 Praxis Dr. med. Volker Shumann Berlin Germany 10245
    80 Studienambulanz emovis GmbH; St. Joseph Krankenhaus Berlin Germany 10626
    81 Charite Campus Benjamin Franklin Berlin Germany 12203
    82 Neurologisch-psychiatrische Praxis am Brosepark Berlin Germany 13156
    83 Bezirkskrankenhaus Günzburg Günzburg Germany 89312
    84 Klinische Forschung Hannover-Mitte GmbH Hannover Germany 30159
    85 Klinikum rechts der Isar der TU München; Klinik & Poliklinik für Neurologie München Germany 81675
    86 ZNS Siegen im MVZ Weidenau Siegen Germany 57076
    87 Universitätsklinik Tübingen; Psychiatrie und Psychotherapie Tubingen Germany 72076
    88 Universitätsklinikum Ulm; Klinik für Neurologie Ulm Germany 89081
    89 Umberto I Policlinico di Roma-Università di Roma La Sapienza Roma Lazio Italy 00185
    90 Ospedale San Giovanni Calibita Fatebenefratell;Neurologia Roma Lazio Italy 00186
    91 Azienda Ospedaliero Universitaria San Martino; Dip. di Neuroscienze Oftalmologia e Genetica Genova Liguria Italy 16132
    92 IRCCS Centro San Giovanni di Dio FBF Brescia Lombardia Italy 25125
    93 Fondazione IRCCS Istituto Neurologico Carlo Besta Milano Lombardia Italy 20133
    94 IRCCS Neuromed; Neurologia I-Centro studio e cura delle demenze e UVA Pozzilli Molise Italy 86077
    95 Az. Osp. C. Panico; Rep. Ematologia E Trapianto Tricase - LE Puglia Italy 73039
    96 Jeroen Bosch Ziekenhuis 'S Hertogenbosch Netherlands 5223 GZ
    97 Brain Research Center B.V Amsterdam Netherlands 1081 GN
    98 Podlaskie Centrum Psychogeriatrii Białystok Poland 15-756
    99 PALLMED Sp. z o.o. prowadząca NZOZ DOM SUE RYDER Bydgoszcz Poland 85-796
    100 M.A. - LEK A.M.Maciejowscy SC. Katowice Poland 40-595
    101 Novo-Med Zielinski i wspolnicy Sp. j. Katowice Poland 40-650
    102 Malopolskie Centrum Medyczne Krakow Poland 30-510
    103 NEURO - KARD Ośrodek Badań Klinicznych Poznań Poland 61-853
    104 NEURO-CARE Sp. z o.o. Sp. Komandytowa Siemianowice Śląskie Poland 41-100
    105 Senior Sp. Z O.O. Poradnia Psychogeriatryczna Sopot Poland 81-855
    106 EroMedis Szczecin Poland 70-11
    107 AMED Medical Center Warszawa Poland 01-518
    108 Centrum Medyczne NeuroProtect Warszawa Poland 01-684
    109 NZOZ WCA Wrocław Poland 53-659
    110 Hospital Mutua de Terrassa Terrassa Barcelona Spain 08221
    111 Policlinica Guipuzcoa San Sebastian Guipuzcoa Spain 20009
    112 Clinica Universitaria de Navarra; Servicio de Neurología Pamplona Navarra Spain 31008
    113 Hospital Virgen del Puerto Plasencia Palencia Spain 10600
    114 Hospital de Cruces; Servicio de Neurologia Barakaldo Vizcaya Spain 48903
    115 Hospital Perpetuo Socorro, Servicio de Geriatria Albacete Spain 2006
    116 Hospital de la Santa Creu i Sant Pau Barcelona Spain 08025
    117 Fundación ACE; Servicio de Neurología Barcelona Spain 08028
    118 Hospital Clinic i Provincial de Barcelona Barcelona Spain 08036
    119 Hospital Universitario Reina Sofia; Servicio de Neurologia Cordoba Spain 14011
    120 Hospital Universitario Ramon y Cajal Madrid Spain 28034
    121 Hospital de Cantoblanco; Servicio de Geriatria Madrid Spain 28049
    122 Hospital Universitario Virgen Macarena Sevilla Spain 41009
    123 Hospital Universitario Dr. Peset; Servicio de Neurologia Valencia Spain 46017
    124 Hospital Universitari i Politecnic La Fe de Valencia Valencia Spain 46026
    125 Länssjukhuset Ryhov Jönköping Sweden 551 85
    126 Länssjukhuset Kalmar; Oncology Kalmar Sweden 39185
    127 Skane University Hospital Malmo/Lund, Dept.of Hematology and Coagulation Disorders Malmö Sweden 212 24
    128 Sahlgrenska Univ Hospital Mölndal; Department of Nephrology Mölndal Sweden S-431 80
    129 Karolinska Universitetssjukhuset Huddinge Stockholm Sweden 171 64
    130 Glasgow Memory Clinic Glasgow United Kingdom G20 0XA
    131 RE:Cognition Health London United Kingdom W1G 9RU
    132 The National Hospital for Neurology & Neurosurgery London United Kingdom WC1N 3BG
    133 Re:Cognition Health Guildford Surrey United Kingdom GU2 7YD

    Sponsors and Collaborators

    • Genentech, Inc.

    Investigators

    • Study Director: Clinical Trials, Genentech, Inc.

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Genentech, Inc.
    ClinicalTrials.gov Identifier:
    NCT03289143
    Other Study ID Numbers:
    • GN39763
    • 2017-001800-31
    First Posted:
    Sep 20, 2017
    Last Update Posted:
    Mar 16, 2022
    Last Verified:
    Feb 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Genentech, Inc.
    Alzheimer Disease
    Brain Diseases
    Dementia
    Neurodegenerative Diseases
    Neurocognitive Disorders
    Additional relevant MeSH terms:
    Alzheimer Disease

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail The study consisted of a double-blind treatment period and an optional open-label extension (OLE) period. OLE period was available to participants who completed the double-blind treatment period and who, in the judgment of the investigator, would potentially benefit from open-label semorinemab treatment.
    Arm/Group Title Placebo Double Blind Period Dose 1 Semorinemab Double Blind Period Dose 2 Semorinemab Double Blind Period Dose 3 Semorinemab Double Blind Period
    Arm/Group Description Matching placebo dose of Semorinemab was administered intravenously in the double-blind treatment period. Semorinemab was administered intravenously at dose 1 in the double-blind treatment period. Semorinemab was administered intravenously at dose 2 in the double-blind treatment period. Semorinemab was administered intravenously at dose 3 in the double-blind treatment period.
    Period Title: Overall Study
    STARTED 135 94 136 92
    COMPLETED 1 0 2 0
    NOT COMPLETED 134 94 134 92

    Baseline Characteristics

    Arm/Group Title Placebo Double Blind Period Dose 1 Semorinemab Double Blind Period Dose 2 Semorinemab Double Blind Period Dose 3 Semorinemab Double Blind Period Total
    Arm/Group Description Matching placebo dose of Semorinemab was administered intravenously in the double-blind treatment period. Semorinemab was administered intravenously at dose 1 in the double-blind treatment period. Semorinemab was administered intravenously at dose 2 in the double-blind treatment period. Semorinemab was administered intravenously at dose 3 in the double-blind treatment period. Total of all reporting groups
    Overall Participants 135 94 136 92 457
    Age (Year) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Year]
    69.7
    (7.3)
    70.2
    (6.7)
    69.3
    (7.1)
    69.6
    (6.7)
    69.6
    (6.9)
    Sex: Female, Male (Count of Participants)
    Female
    75
    55.6%
    51
    54.3%
    79
    58.1%
    48
    52.2%
    253
    55.4%
    Male
    60
    44.4%
    43
    45.7%
    57
    41.9%
    44
    47.8%
    204
    44.6%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    0.7%
    4
    4.3%
    5
    3.7%
    3
    3.3%
    13
    2.8%
    Not Hispanic or Latino
    126
    93.3%
    80
    85.1%
    125
    91.9%
    79
    85.9%
    410
    89.7%
    Unknown or Not Reported
    8
    5.9%
    10
    10.6%
    6
    4.4%
    10
    10.9%
    34
    7.4%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    1
    1.1%
    0
    0%
    0
    0%
    1
    0.2%
    Asian
    0
    0%
    1
    1.1%
    2
    1.5%
    0
    0%
    3
    0.7%
    Native Hawaiian or Other Pacific Islander
    1
    0.7%
    0
    0%
    0
    0%
    0
    0%
    1
    0.2%
    Black or African American
    0
    0%
    2
    2.1%
    1
    0.7%
    1
    1.1%
    4
    0.9%
    White
    129
    95.6%
    83
    88.3%
    128
    94.1%
    82
    89.1%
    422
    92.3%
    More than one race
    1
    0.7%
    1
    1.1%
    0
    0%
    0
    0%
    2
    0.4%
    Unknown or Not Reported
    4
    3%
    6
    6.4%
    5
    3.7%
    9
    9.8%
    24
    5.3%

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline on the CDR-SB
    Description The Clinical Dementia Rating-Sum of Boxes (CDR-SB) rates impairment in 6 categories (memory, orientation, judgement and problem solving, community affairs, home and hobbies and personal care) on a 5-point scale in which no impairment = 0, questionable impairment = 0.5 and mild, moderate and severe impairment = 1, 2 and 3 respectively. The score range is from 0 to 18 with a high score indicating a high disease severity. The difference in mean change from Baseline to Week 73 between Semorinemab doses and Placebo treated participants was estimated. The difference in mean change from Baseline to Week 73 between Semorinemab doses and Placebo treated participants was estimated.
    Time Frame Baseline and 73 Weeks

    Outcome Measure Data

    Analysis Population Description
    Modified intent-to-treat (mITT) population included all randomized participants who received at least one dose of study drug and had at least one postbaseline primary efficacy Clinical Dementia Rating-Sum of Boxes (CDR-SB) measurement.
    Arm/Group Title Placebo Double Blind Period Dose 1 Semorinemab Double Blind Period Dose 2 Semorinemab Double Blind Period Dose 3 Semorinemab Double Blind Period
    Arm/Group Description Matching placebo dose of Semorinemab was administered intravenously in the double-blind treatment period. Semorinemab was administered intravenously at dose 1 in the double-blind treatment period. Semorinemab was administered intravenously at dose 2 in the double-blind treatment period. Semorinemab was administered intravenously at dose 3 in the double-blind treatment period.
    Measure Participants 105 77 113 74
    Mean (Standard Error) [Units on a scale]
    2.19
    (0.226)
    2.36
    (0.268)
    2.36
    (0.222)
    2.41
    (0.27)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Double Blind Period, Dose 1 Semorinemab Double Blind Period
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.6147
    Comments Unadjusted
    Method Mixed-effect Model Repeated Measures
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo Double Blind Period, Dose 2 Semorinemab Double Blind Period
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.5778
    Comments Unadjusted
    Method Mixed-effect Model Repeated Measures
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo Double Blind Period, Dose 3 Semorinemab Double Blind Period
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.5136
    Comments Unadjusted
    Method Mixed-effect Model Repeated Measures
    Comments
    2. Primary Outcome
    Title Percentage of Participants With Adverse Events
    Description Percentage of participants with at least one adverse event
    Time Frame Up to the data cutoff date 15 January 2021 (up to approximately 39 months)

    Outcome Measure Data

    Analysis Population Description
    The safety-evaluable population included all participants who were randomly allocated and received at least one dose of study drug (MTAU9937A or placebo) during the double-blind treatment period with treatment groups defined according to actual treatment received.
    Arm/Group Title Placebo Double Blind Period Dose 1 Semorinemab Double Blind Period Dose 2 Semorinemab Double Blind Period Dose 3 Semorinemab Double Blind Period Dose 2 Semorinemab Open Label Extension Period
    Arm/Group Description Matching placebo dose of Semorinemab was administered intravenously in the double-blind treatment period. Semorinemab was administered intravenously at dose 1 in the double-blind treatment period. Semorinemab was administered intravenously at dose 2 in the double-blind treatment period. Semorinemab was administered intravenously at dose 3 in the double-blind treatment period. Semorinemab was administered intravenously at dose 2 in the open-label extension period.
    Measure Participants 130 89 132 90 360
    Number [Percentage of participants]
    93.1
    69%
    88.8
    94.5%
    94.7
    69.6%
    92.2
    100.2%
    47.5
    10.4%
    3. Secondary Outcome
    Title Change From Baseline on the Repeatable Battery for Assessment of Neuropsychological Status (RBANS)
    Description The RBANS is a validated neuropsychological assessment has been shown to be a useful tool in both clinical and research settings. The RBANS consists of ten subtests that are combined to provide five indices, one for each of the five domains tested (immediate memory, visuospatial/constructional, language, attention, and delayed memory). Scores range from 40 to 160 and a higher score indicates better cognitive functioning. A decrease in the outcome measure from baseline corresponds to disease worsening. The difference in mean change from Baseline to Week 73 between Semorinemab doses and Placebo treated participants was estimated.
    Time Frame Baseline and 73 weeks

    Outcome Measure Data

    Analysis Population Description
    Modified intent-to-treat (mITT) population included all randomized participants who received at least one dose of study drug and had at least one postbaseline primary efficacy Clinical Dementia Rating-Sum of Boxes (CDR-SB) measurement.
    Arm/Group Title Placebo Double Blind Period Dose 1 Semorinemab Double Blind Period Dose 2 Semorinemab Double Blind Period Dose 3 Semorinemab Double Blind Period
    Arm/Group Description Matching placebo dose of Semorinemab was administered intravenously in the double-blind treatment period. Semorinemab was administered intravenously at dose 1 in the double-blind treatment period. Semorinemab was administered intravenously at dose 2 in the double-blind treatment period. Semorinemab was administered intravenously at dose 3 in the double-blind treatment period.
    Measure Participants 87 62 93 63
    Mean (Standard Error) [Score on a scale]
    -5.53
    (0.787)
    -5.25
    (0.93)
    -4.62
    (0.765)
    -6.15
    (0.926)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Double Blind Period, Dose 1 Semorinemab Double Blind Period
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.8198
    Comments Unadjusted
    Method Mixed-effect Model Repeated Measures
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo Double Blind Period, Dose 2 Semorinemab Double Blind Period
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3961
    Comments Unadjusted
    Method Mixed-effect Model Repeated Measures
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo Double Blind Period, Dose 3 Semorinemab Double Blind Period
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.6043
    Comments Unadjusted
    Method Mixed-effect Model Repeated Measures
    Comments
    4. Secondary Outcome
    Title Change From Baseline on the Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog-13) Subscale Score
    Description The ADAS-Cog-13 assesses multiple cognitive domains including memory, comprehension, praxis, orientation, and spontaneous speech. Most of these are assessed by tests although some are rated by the clinician on a 5-point scale. The ADAS-Cog-13 is the ADAS-Cog-11 with 2 further items: delayed word recall and total digit cancellation. The score range for ADAS-Cog-13 is from 0 to 85 with high scores representing severe dysfunction. The difference in mean change from Baseline to Week 73 between Semorinemab doses and Placebo treated participants was estimated.
    Time Frame Baseline and 73 weeks

    Outcome Measure Data

    Analysis Population Description
    Modified intent-to-treat (mITT) population included all randomized participants who received at least one dose of study drug and had at least one postbaseline primary efficacy Clinical Dementia Rating-Sum of Boxes (CDR-SB) measurement.
    Arm/Group Title Placebo Double Blind Period Dose 1 Semorinemab Double Blind Period Dose 2 Semorinemab Double Blind Period Dose 3 Semorinemab Double Blind Period
    Arm/Group Description Matching placebo dose of Semorinemab was administered intravenously in the double-blind treatment period. Semorinemab was administered intravenously at dose 1 in the double-blind treatment period. Semorinemab was administered intravenously at dose 2 in the double-blind treatment period. Semorinemab was administered intravenously at dose 3 in the double-blind treatment period.
    Measure Participants 94 67 97 66
    Mean (Standard Error) [Score on a scale]
    6.56
    (0.777)
    8.68
    (0.937)
    6
    (0.769)
    7.58
    (0.932)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Double Blind Period, Dose 1 Semorinemab Double Blind Period
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0783
    Comments Unadjusted
    Method Mixed-effect Model Repeated Measures
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo Double Blind Period, Dose 2 Semorinemab Double Blind Period
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.6010
    Comments Unadjusted
    Method Mixed-effect Model Repeated Measures
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo Double Blind Period, Dose 3 Semorinemab Double Blind Period
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3961
    Comments Unadjusted
    Method Mixed-effect Model Repeated Measures
    Comments
    5. Secondary Outcome
    Title Change From Baseline on the Amsterdam Instrumental Activity of Daily Living (iADL) Questionnaire
    Description The Amsterdam iADL questionnaire is an informant-based instrument for measuring iADL problems in participants with dementia. This instrument consists of 70 items, scored on a 5-point scale, that uses item response theory for scoring. Items presented to the informant are tailored to responses to earlier items; thus each administration of the Amsterdam iADL may consist of less than the total of 70 items. The resulting score ranges from 20 to 80 with lower scores indicating poorer performance. A decrease in the outcome measure from baseline corresponds to disease worsening. The difference in mean change from Baseline to Week 73 between Semorinemab doses and Placebo treated participants was estimated.
    Time Frame Baseline and 73 weeks

    Outcome Measure Data

    Analysis Population Description
    Modified intent-to-treat (mITT) population included all randomized participants who received at least one dose of study drug and had at least one postbaseline primary efficacy Clinical Dementia Rating-Sum of Boxes (CDR-SB) measurement.
    Arm/Group Title Placebo Double Blind Period Dose 1 Semorinemab Double Blind Period Dose 2 Semorinemab Double Blind Period Dose 3 Semorinemab Double Blind Period
    Arm/Group Description Matching placebo dose of Semorinemab was administered intravenously in the double-blind treatment period. Semorinemab was administered intravenously at dose 1 in the double-blind treatment period. Semorinemab was administered intravenously at dose 2 in the double-blind treatment period. Semorinemab was administered intravenously at dose 3 in the double-blind treatment period.
    Measure Participants 95 70 109 67
    Mean (Standard Error) [Score on a scale]
    -6.59
    (0.856)
    -6.55
    (0.999)
    -6.92
    (0.824)
    -7.31
    (1.013)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Double Blind Period, Dose 1 Semorinemab Double Blind Period
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.9749
    Comments Unadjusted
    Method Mixed-effect Model Repeated Measures
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo Double Blind Period, Dose 2 Semorinemab Double Blind Period
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.7718
    Comments Unadjusted
    Method Mixed-effect Model Repeated Measures
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo Double Blind Period, Dose 3 Semorinemab Double Blind Period
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.5789
    Comments Unadjusted
    Method Mixed-effect Model Repeated Measures
    Comments
    6. Secondary Outcome
    Title Change From Baseline on the Alzheimer's Disease Cooperative Study Group-Activities of Daily Living Inventory
    Description The ADCS-ADL (Alzheimer's Disease Cooperative Study-Activities of Daily Living) is the scale most widely used to assess functional outcomes in participants with AD. The ADCS-ADL covers both basic ADL (e.g., eating and toileting) and more complex 'instrumental' ADL or iADL (e.g., using the telephone, managing finances and preparing a meal). The ADCS-ADL consists of 23 questions with a score range of 0 to 78 where a higher score represents better function. The difference in mean change from Baseline to Week 73 between Semorinemab doses and Placebo treated participants was estimated.
    Time Frame Baseline and 73 weeks

    Outcome Measure Data

    Analysis Population Description
    Modified intent-to-treat (mITT) population included all randomized participants who received at least one dose of study drug and had at least one postbaseline primary efficacy Clinical Dementia Rating-Sum of Boxes (CDR-SB) measurement.
    Arm/Group Title Placebo Double Blind Period Dose 1 Semorinemab Double Blind Period Dose 2 Semorinemab Double Blind Period Dose 3 Semorinemab Double Blind Period
    Arm/Group Description Matching placebo dose of Semorinemab was administered intravenously in the double-blind treatment period. Semorinemab was administered intravenously at dose 1 in the double-blind treatment period. Semorinemab was administered intravenously at dose 2 in the double-blind treatment period. Semorinemab was administered intravenously at dose 3 in the double-blind treatment period.
    Measure Participants 104 76 112 74
    Mean (Standard Error) [Score on a scale]
    -8.55
    (0.996)
    -9.52
    (1.179)
    -7.75
    (0.986)
    -7.99
    (1.183)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Double Blind Period, Dose 1 Semorinemab Double Blind Period
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.5235
    Comments Unadjusted
    Method Mixed-effect Model Repeated Measures
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo Double Blind Period, Dose 2 Semorinemab Double Blind Period
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.5612
    Comments Unadjusted
    Method Mixed-effect Model Repeated Measures
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo Double Blind Period, Dose 3 Semorinemab Double Blind Period
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.7130
    Comments Unadjusted
    Method Mixed-effect Model Repeated Measures
    Comments
    7. Secondary Outcome
    Title Serum Concentrations of Semorinemab at Specified Timepoints
    Description Serum concentrations of Semorinemab at specified timepoints.
    Time Frame Up to 109 weeks

    Outcome Measure Data

    Analysis Population Description
    The PK-evaluable population is defined as patients who received Semorinemab treatment and had at least one measureable PK concentration.
    Arm/Group Title Dose 1 Semorinemab Double Blind and Open Label Extension Periods Dose 2 Semorinemab Double Blind and Open Label Extension Periods Dose 3 Semorinemab Double Blind and Open Label Extension Periods
    Arm/Group Description Semorinemab was administered intravenously at dose 1 in the double-blind treatment period. Optional Open Label Extension was available to participants who completed the double-blind treatment period and who, in the judgment of the investigator, would potentially benefit from open-label extension. Semorinemab was administered intravenously at dose 2 in the double-blind treatment period. Optional Open Label Extension was available to participants who completed the double-blind treatment period and who, in the judgment of the investigator, would potentially benefit from open-label extension. Semorinemab was administered intravenously at dose 3 in the double-blind treatment period. Optional Open Label Extension was available to participants who completed the double-blind treatment period and who, in the judgment of the investigator, would potentially benefit from open-label extension.
    Measure Participants 89 132 90
    Week 1, 0-4 Hours Predose
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    Week 1, 1 Hour Postdose
    472
    (131)
    1580
    (496)
    2690
    (689)
    Week 1, 2 Hours Postdose
    476
    (123)
    1510
    (419)
    2600
    (707)
    Week 1, 4 Hours postdose
    463
    (135)
    1370
    (405)
    2570
    (785)
    Week 3, 0-4 hours Predose
    184
    (52.7)
    601
    (211)
    1100
    (449)
    Week 3, 30 min Post dose
    718
    (198)
    2320
    (581)
    4190
    (1010)
    Week 5, 0-4 Hours Predose
    318
    (81.5)
    955
    (256)
    1920
    (614)
    Week 5, 30 min Postdose
    908
    (508)
    2780
    (695)
    4860
    (1250)
    Week 9, 0-4 hours Predose
    344
    (128)
    961
    (288)
    1840
    (513)
    Week 9, 30 Minutes Postdose
    889
    (321)
    2790
    (757)
    4960
    (1270)
    Week 13, 0-4 Hours Predose
    360
    (105)
    1060
    (333)
    1910
    (545)
    Week 13, 30 Minutes Postdose
    998
    (896)
    2900
    (668)
    4880
    (1250)
    Week 17
    1750
    (NA)
    Week 17, 0-4 Hours Predose
    386
    (116)
    1040
    (316)
    1890
    (522)
    Week 17, 30 Minutes Postdose
    819
    (242)
    2930
    (902)
    4770
    (1270)
    Week 33, 0-4 Hours Predose
    404
    (134)
    960
    (277)
    2050
    (648)
    Week 33, 30 Minutes Postdose
    801
    (260)
    2540
    (853)
    4800
    (1200)
    Week 49, 0-4 Hours Predose
    377
    (105)
    1060
    (332)
    2160
    (605)
    Week 49, 30 Minutes Postdose
    871
    (260)
    2810
    (967)
    4960
    (1030)
    Week 65
    2100
    (NA)
    Week 65, 0-4 Hours Predose
    405
    (127)
    1170
    (276)
    2020
    (681)
    Week 65, 30 Minutes Postdose
    963
    (401)
    2930
    (830)
    4710
    (1450)
    Week 73
    327
    (154)
    1030
    (451)
    1830
    (752)
    Week 73, 0-4 Hours Predose
    382
    (NA)
    Week 73, 1 Hour Postdose
    1910
    (NA)
    Week 73, 2 Hours Postdose
    1740
    (NA)
    Week 73, 4 Hours Postdose
    1710
    (NA)
    Week 77 OLE, 0-4 Hours Predose
    180
    (71.0)
    724
    (167)
    1030
    (345)
    Week 77 OLE, 1 hour Postdose
    1700
    (523)
    2460
    (868)
    2670
    (707)
    Week 77 OLE, 2 hours Postdose
    1830
    (552)
    2270
    (442)
    2510
    (579)
    Week 77 OLE, 4 hours Postdose
    1850
    (516)
    2270
    (480)
    2790
    (558)
    Week 93 OLE, 0-4 Hours Pre-dose
    632
    (37.5)
    1040
    (113)
    1290
    (307)
    Week 93 OLE, 30 Minutes Postdose
    1920
    (431)
    2570
    (91.9)
    2880
    (492)
    Week 109 OLE, 0-4 Hours Predose
    1270
    (NA)
    Week 109 OLE, 30 Minutes Postdose
    3330
    (NA)
    8. Secondary Outcome
    Title Presence of Anti-drug Antibodies During the Study Relative to Their Presence at Baseline
    Description Presence of anti-drug antibodies during the study relative to their presence at baseline.
    Time Frame Up to 109 weeks

    Outcome Measure Data

    Analysis Population Description
    The immunogenicity analyses will include participants with at least one predose and one postdose ADA assessment, with participants grouped according to treatment arm.
    Arm/Group Title Placebo Double Blind Period Dose 1 Semorinemab Double Blind Period Dose 2 Semorinemab Double Blind Period Dose 3 Semorinemab Double Blind Period
    Arm/Group Description Matching placebo dose of Semorinemab was administered intravenously in the double-blind treatment period. Semorinemab was administered intravenously at dose 1 in the double-blind treatment period. Semorinemab was administered intravenously at dose 2 in the double-blind treatment period. Semorinemab was administered intravenously at dose 3 in the double-blind treatment period.
    Measure Participants 130 89 132 90
    Baseline
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Post-baseline
    0
    0%
    0
    0%
    0
    0%
    9. Primary Outcome
    Title Change From Baseline on the C-SSRS
    Description Categories are as defined in the Classification Algorithm for Suicide Assessment (CASA) based on the Columbia Suicide Severity Rating Scale (C-SSRS) questionnaire. SI1: Passive category is "Wish to be dead", SI2: Active-Nonspecific (no method, intent or plan), SI3: Active-Method, but no intent or Plan, SI4: Active-Method and intent, but no plan in C-SSRS. The worst post-baseline suicidal ideation is the highest across post-baseline visits, with highest as SI5 and lowest as SI1. Percentages are based on the total number of subjects in a treatment group. Baseline is the last observation prior to initiation of study drug.
    Time Frame Baseline to data cutoff date 15 January 2021 (up to approximately 39 months)

    Outcome Measure Data

    Analysis Population Description
    The safety-evaluable population included all participants who were randomly allocated and received at least one dose of study drug (MTAU9937A or placebo) during the double-blind treatment period with treatment groups defined according to actual treatment received.
    Arm/Group Title Placebo Double Blind Period Dose 1 Semorinemab Double Blind Period Dose 2 Semorinemab Double Blind Period Dose 3 Semorinemab Double Blind Period Dose 2 Semorinemab Open Label Extension Period
    Arm/Group Description Matching placebo dose of Semorinemab was administered intravenously in the double-blind treatment period. Semorinemab was administered intravenously at dose 1 in the double-blind treatment period. Semorinemab was administered intravenously at dose 2 in the double-blind treatment period. Semorinemab was administered intravenously at dose 3 in the double-blind treatment period. Semorinemab was administered intravenously at dose 2 in the open-label extension period.
    Measure Participants 130 89 132 90 360
    Missing/No Events
    1
    0.7%
    1
    1.1%
    2
    1.5%
    0
    0%
    3
    0.7%
    Missing/SI1
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Missing/SI2
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Missing/SI3
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Missing/SI4
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Missing/Missing
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    No Event/No Event
    119
    88.1%
    80
    85.1%
    123
    90.4%
    83
    90.2%
    336
    73.5%
    No Event/SI1
    3
    2.2%
    3
    3.2%
    2
    1.5%
    4
    4.3%
    5
    1.1%
    No Event/ SI2
    0
    0%
    1
    1.1%
    1
    0.7%
    0
    0%
    1
    0.2%
    No Event/SI3
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    No Event/ SI4
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    No Event/ Missing
    1
    0.7%
    0
    0%
    0
    0%
    1
    1.1%
    1
    0.2%
    SI1/No Event
    3
    2.2%
    3
    3.2%
    1
    0.7%
    1
    1.1%
    8
    1.8%
    SI1/SI1
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    0.2%
    SI1/SI2
    1
    0.7%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    SI1/SI3
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    SI1/SI4
    1
    0.7%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    SI1/Missing
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    SI2/No Event
    0
    0%
    1
    1.1%
    2
    1.5%
    0
    0%
    1
    0.2%
    SI2/SI1
    0
    0%
    0
    0%
    1
    0.7%
    0
    0%
    2
    0.4%
    SI2/SI2
    0
    0%
    0
    0%
    0
    0%
    1
    1.1%
    0
    0%
    SI2/SI3
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    SI2/SI4
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    SI2/Missing
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    SI3/No Event
    1
    0.7%
    0
    0%
    0
    0%
    0
    0%
    1
    0.2%
    SI3/SI1
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    SI3/SI2
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    SI3/SI3
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    SI3/SI4
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    SI3/Missing
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    SI4/No Event
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    SI4/SI1
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    SI4/SI2
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    SI4/SI3
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    0.2%
    SI4/Missing
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    10. Primary Outcome
    Title Other Abnormal MRI Findings
    Description Other abnormal MRI findings by visit. For the Double Blind Period, baseline is defined as last results prior to initiation of study drug. For the Open Label Extension Period, baseline is defined as last results prior to entering the open label period.
    Time Frame Baseline, Week 9, Week 49, Week 73, Study Treatment Discontinuation, and Week 89

    Outcome Measure Data

    Analysis Population Description
    The safety-evaluable population included all participants who were randomly allocated and received at least one dose of study drug (MTAU9937A or placebo) during the double-blind treatment period with treatment groups defined according to actual treatment received.
    Arm/Group Title Placebo Double Blind Period Dose 1 Semorinemab Double Blind Period Dose 2 Semorinemab Double Blind Period Dose 3 Semorinemab Double Blind Period Dose 2 Semorinemab Open Label Extension Period
    Arm/Group Description Matching placebo dose of Semorinemab was administered intravenously in the double-blind treatment period. Semorinemab was administered intravenously at dose 1 in the double-blind treatment period. Semorinemab was administered intravenously at dose 2 in the double-blind treatment period. Semorinemab was administered intravenously at dose 3 in the double-blind treatment period. Semorinemab was administered intravenously at dose 2 in the open-label extension period.
    Measure Participants 135 94 136 92 360
    Cerebrovascular Pathology, Baseline
    3
    2.2%
    0
    0%
    2
    1.5%
    1
    1.1%
    5
    1.1%
    CNS Trauma, Baseline
    0
    0%
    0
    0%
    0
    0%
    1
    1.1%
    1
    0.2%
    Intracranial Tumor, Baseline
    0
    0%
    0
    0%
    3
    2.2%
    2
    2.2%
    4
    0.9%
    Lacunar Infarct, Baseline
    13
    9.6%
    3
    3.2%
    11
    8.1%
    6
    6.5%
    23
    5%
    Superficial Hemosiderosis, Baseline
    3
    2.2%
    0
    0%
    2
    1.5%
    0
    0%
    7
    1.5%
    Territorial Infarct, Baseline
    3
    2.2%
    1
    1.1%
    0
    0%
    0
    0%
    4
    0.9%
    Vasogenic Edema/Sulcal Effusion, Baseline
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Cerebrovascular Pathology, Week 9
    0
    0%
    1
    1.1%
    0
    0%
    0
    0%
    CNS Trauma, Week 9
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Intracranial Tumor, Week 9
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Lacunar Infarct, Week 9
    0
    0%
    1
    1.1%
    0
    0%
    0
    0%
    Superficial Hemosiderosis, Week 9
    3
    2.2%
    0
    0%
    0
    0%
    1
    1.1%
    Territorial Infarct, Week 9
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Vasogenic Edema/Sulcal Effusion, Week 9
    0
    0%
    0
    0%
    1
    0.7%
    0
    0%
    Cerebrovascular Pathology, Week 49
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    CNS Trauma, Week 49
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Intracranial Tumor, Week 49
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Lacunar Infarct, Week 49
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Superficial Hemosiderosis, Week 49
    1
    0.7%
    1
    1.1%
    1
    0.7%
    0
    0%
    Territorial Infarct, Week 49
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Vasogenic Edema/Sulcal Effusion, Week 49
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Cerebrovascular Pathology, Week 73
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    CNS Trauma, Week 73
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Intracranial Tumor, Week 73
    1
    0.7%
    0
    0%
    0
    0%
    0
    0%
    Lacunar Infarct, Week 73
    0
    0%
    1
    1.1%
    0
    0%
    0
    0%
    Superficial Hemosiderosis, Week 73
    0
    0%
    1
    1.1%
    0
    0%
    1
    1.1%
    Territorial Infarct, Week 73
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Vasogenic Edema/Sulcal Effusion, Week 73
    1
    0.7%
    0
    0%
    0
    0%
    0
    0%
    Cerebrovascular Pathology, Study Treatment Early Discontinuation
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    CSN Trauma, Study Treatment Early Discontinuation
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Intracranial Tumor, Study Treatment Early Discontinuation
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Lucunar Infarct, Study Treatment Early Discontinuation
    1
    0.7%
    0
    0%
    0
    0%
    0
    0%
    Superficial Hemosiderosis, Study Treatment Early Discontinuation
    1
    0.7%
    0
    0%
    0
    0%
    0
    0%
    Territorial Infarct, Study Treatment Early Discontinuation
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Vasogenic Edema/Sulcal Effusion, Study Treatment Early Discontinuation
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Cerebrovascular Pathology, Week 89 Open Label Extension (OLE)
    0
    0%
    CNS Trauma, Week 89 OLE
    0
    0%
    Intracranial Tumor, Week 89 OLE
    1
    0.7%
    Lacunar Infarct, Week 89 OLE
    0
    0%
    Superficial Hemosiderosis, Week 89 OLE
    0
    0%
    Territorial Infarct, Week 89 OLE
    0
    0%
    Vasogenic Edema/Sulcal Effusion, Week 89 OLE
    1
    0.7%

    Adverse Events

    Time Frame From the first study drug to the data cutoff date: 15 January 2021 (up to approximately 39 months)
    Adverse Event Reporting Description The safety-evaluable population included all participants who were randomly allocated and received at least one dose of study drug (semorinemab or placebo) during the double-blind treatment period with treatment groups defined according to actual treatment received.
    Arm/Group Title Placebo Double Blind Period Dose 1 Semorinemab Double Blind Period Dose 2 Semorinemab Double Blind Period Dose 3 Semorinemab Double Blind Period Dose 2 Semorinemab Open Label
    Arm/Group Description Matching placebo dose of Semorinemab was administered intravenously in the double-blind treatment period. Semorinemab was administered intravenously at dose 1 in the double-blind treatment period. Semorinemab was administered intravenously at dose 2 in the double-blind treatment period. Semorinemab was administered intravenously at dose 3 in the double-blind treatment period. Semorinemab was administered intravenously at dose 2 in the open-label extension period.
    All Cause Mortality
    Placebo Double Blind Period Dose 1 Semorinemab Double Blind Period Dose 2 Semorinemab Double Blind Period Dose 3 Semorinemab Double Blind Period Dose 2 Semorinemab Open Label
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/130 (1.5%) 0/89 (0%) 1/132 (0.8%) 1/90 (1.1%) 1/360 (0.3%)
    Serious Adverse Events
    Placebo Double Blind Period Dose 1 Semorinemab Double Blind Period Dose 2 Semorinemab Double Blind Period Dose 3 Semorinemab Double Blind Period Dose 2 Semorinemab Open Label
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 14/130 (10.8%) 17/89 (19.1%) 17/132 (12.9%) 16/90 (17.8%) 17/360 (4.7%)
    Blood and lymphatic system disorders
    Anaemia 0/130 (0%) 0 1/89 (1.1%) 1 0/132 (0%) 0 0/90 (0%) 0 0/360 (0%) 0
    Cardiac disorders
    Angina unstable 1/130 (0.8%) 1 0/89 (0%) 0 0/132 (0%) 0 0/90 (0%) 0 0/360 (0%) 0
    Atrial fibrillation 0/130 (0%) 0 0/89 (0%) 0 0/132 (0%) 0 0/90 (0%) 0 1/360 (0.3%) 1
    Atrioventricular block 0/130 (0%) 0 0/89 (0%) 0 0/132 (0%) 0 0/90 (0%) 0 1/360 (0.3%) 1
    Bradycardia 0/130 (0%) 0 0/89 (0%) 0 1/132 (0.8%) 1 0/90 (0%) 0 0/360 (0%) 0
    Cardiac arrest 0/130 (0%) 0 0/89 (0%) 0 0/132 (0%) 0 0/90 (0%) 0 1/360 (0.3%) 1
    Congestive cardiomyopathy 0/130 (0%) 0 0/89 (0%) 0 1/132 (0.8%) 1 0/90 (0%) 0 0/360 (0%) 0
    Coronary artery disease 1/130 (0.8%) 1 0/89 (0%) 0 0/132 (0%) 0 0/90 (0%) 0 0/360 (0%) 0
    Myocardial infarction 0/130 (0%) 0 0/89 (0%) 0 1/132 (0.8%) 1 0/90 (0%) 0 0/360 (0%) 0
    Sinus node dysfunction 0/130 (0%) 0 1/89 (1.1%) 1 0/132 (0%) 0 0/90 (0%) 0 0/360 (0%) 0
    Ventricular fibrillation 0/130 (0%) 0 0/89 (0%) 0 0/132 (0%) 0 0/90 (0%) 0 1/360 (0.3%) 1
    Eye disorders
    Retinal detachment 1/130 (0.8%) 1 0/89 (0%) 0 0/132 (0%) 0 0/90 (0%) 0 0/360 (0%) 0
    Gastrointestinal disorders
    Abdominal pain 0/130 (0%) 0 0/89 (0%) 0 0/132 (0%) 0 0/90 (0%) 0 1/360 (0.3%) 1
    Enteritis 0/130 (0%) 0 1/89 (1.1%) 1 0/132 (0%) 0 0/90 (0%) 0 0/360 (0%) 0
    Haemorrhoids 0/130 (0%) 0 1/89 (1.1%) 1 0/132 (0%) 0 0/90 (0%) 0 0/360 (0%) 0
    Inguinal hernia 0/130 (0%) 0 0/89 (0%) 0 0/132 (0%) 0 0/90 (0%) 0 1/360 (0.3%) 1
    Inguinal hernia strangulated 0/130 (0%) 0 0/89 (0%) 0 0/132 (0%) 0 1/90 (1.1%) 1 0/360 (0%) 0
    Large intestine perforation 1/130 (0.8%) 1 0/89 (0%) 0 0/132 (0%) 0 0/90 (0%) 0 0/360 (0%) 0
    Lower gastrointestinal haemorrhage 0/130 (0%) 0 1/89 (1.1%) 1 0/132 (0%) 0 0/90 (0%) 0 0/360 (0%) 0
    Pancreatitis 0/130 (0%) 0 0/89 (0%) 0 0/132 (0%) 0 1/90 (1.1%) 1 0/360 (0%) 0
    Rectal polyp 0/130 (0%) 0 1/89 (1.1%) 1 0/132 (0%) 0 0/90 (0%) 0 0/360 (0%) 0
    General disorders
    Chest pain 0/130 (0%) 0 1/89 (1.1%) 1 0/132 (0%) 0 0/90 (0%) 0 0/360 (0%) 0
    Euthanasia 0/130 (0%) 0 0/89 (0%) 0 0/132 (0%) 0 1/90 (1.1%) 1 0/360 (0%) 0
    Sudden death 1/130 (0.8%) 1 0/89 (0%) 0 0/132 (0%) 0 0/90 (0%) 0 0/360 (0%) 0
    Hepatobiliary disorders
    Bile duct stone 0/130 (0%) 0 0/89 (0%) 0 0/132 (0%) 0 0/90 (0%) 0 1/360 (0.3%) 1
    Cholecystitis 0/130 (0%) 0 0/89 (0%) 0 0/132 (0%) 0 0/90 (0%) 0 1/360 (0.3%) 1
    Cholelithiasis 0/130 (0%) 0 0/89 (0%) 0 0/132 (0%) 0 1/90 (1.1%) 1 0/360 (0%) 0
    Infections and infestations
    COVID-19 0/130 (0%) 0 0/89 (0%) 0 1/132 (0.8%) 1 0/90 (0%) 0 0/360 (0%) 0
    Clostridium difficile colitis 0/130 (0%) 0 1/89 (1.1%) 1 1/132 (0.8%) 1 1/90 (1.1%) 1 0/360 (0%) 0
    Diverticulitis 0/130 (0%) 0 1/89 (1.1%) 1 0/132 (0%) 0 0/90 (0%) 0 0/360 (0%) 0
    Parainfluenzae virus infection 0/130 (0%) 0 0/89 (0%) 0 0/132 (0%) 0 1/90 (1.1%) 1 0/360 (0%) 0
    Peritonsillar abscess 0/130 (0%) 0 0/89 (0%) 0 1/132 (0.8%) 1 0/90 (0%) 0 0/360 (0%) 0
    Pneumonia 1/130 (0.8%) 1 1/89 (1.1%) 1 1/132 (0.8%) 1 3/90 (3.3%) 3 1/360 (0.3%) 1
    Septic shock 1/130 (0.8%) 1 0/89 (0%) 0 0/132 (0%) 0 0/90 (0%) 0 0/360 (0%) 0
    Staphylococcal bacteraemia 0/130 (0%) 0 0/89 (0%) 0 0/132 (0%) 0 0/90 (0%) 0 1/360 (0.3%) 1
    Tooth abscess 0/130 (0%) 0 1/89 (1.1%) 1 0/132 (0%) 0 0/90 (0%) 0 0/360 (0%) 0
    Urinary tract infection 0/130 (0%) 0 1/89 (1.1%) 1 0/132 (0%) 0 1/90 (1.1%) 1 1/360 (0.3%) 1
    Viral upper respiratory tract infection 0/130 (0%) 0 0/89 (0%) 0 0/132 (0%) 0 1/90 (1.1%) 1 0/360 (0%) 0
    Injury, poisoning and procedural complications
    Craniocerebral injury 0/130 (0%) 0 1/89 (1.1%) 1 0/132 (0%) 0 0/90 (0%) 0 0/360 (0%) 0
    Face injury 0/130 (0%) 0 0/89 (0%) 0 1/132 (0.8%) 1 0/90 (0%) 0 0/360 (0%) 0
    Fall 2/130 (1.5%) 2 0/89 (0%) 0 1/132 (0.8%) 1 1/90 (1.1%) 1 0/360 (0%) 0
    Femoral neck fracture 1/130 (0.8%) 1 0/89 (0%) 0 0/132 (0%) 0 0/90 (0%) 0 0/360 (0%) 0
    Femur fracture 1/130 (0.8%) 1 0/89 (0%) 0 0/132 (0%) 0 0/90 (0%) 0 1/360 (0.3%) 1
    Foot fracture 0/130 (0%) 0 1/89 (1.1%) 1 0/132 (0%) 0 0/90 (0%) 0 0/360 (0%) 0
    Fracture displacement 0/130 (0%) 0 0/89 (0%) 0 0/132 (0%) 0 0/90 (0%) 0 1/360 (0.3%) 1
    Hip fracture 0/130 (0%) 0 1/89 (1.1%) 1 2/132 (1.5%) 2 0/90 (0%) 0 0/360 (0%) 0
    Lumbar vertebral fracture 0/130 (0%) 0 1/89 (1.1%) 1 0/132 (0%) 0 0/90 (0%) 0 0/360 (0%) 0
    Road traffic accident 1/130 (0.8%) 1 0/89 (0%) 0 1/132 (0.8%) 1 0/90 (0%) 0 0/360 (0%) 0
    Skin wound 0/130 (0%) 0 0/89 (0%) 0 1/132 (0.8%) 1 0/90 (0%) 0 0/360 (0%) 0
    Spinal compression fracture 0/130 (0%) 0 0/89 (0%) 0 1/132 (0.8%) 1 0/90 (0%) 0 1/360 (0.3%) 1
    Spinal fracture 0/130 (0%) 0 0/89 (0%) 0 1/132 (0.8%) 1 0/90 (0%) 0 0/360 (0%) 0
    Investigations
    Blood pressure increased 0/130 (0%) 0 0/89 (0%) 0 1/132 (0.8%) 1 0/90 (0%) 0 0/360 (0%) 0
    Metabolism and nutrition disorders
    Dehydration 0/130 (0%) 0 1/89 (1.1%) 1 0/132 (0%) 0 0/90 (0%) 0 0/360 (0%) 0
    Diabetes mellitus inadequate control 1/130 (0.8%) 1 0/89 (0%) 0 0/132 (0%) 0 0/90 (0%) 0 0/360 (0%) 0
    Musculoskeletal and connective tissue disorders
    Back pain 0/130 (0%) 0 0/89 (0%) 0 1/132 (0.8%) 1 0/90 (0%) 0 0/360 (0%) 0
    Bursitis 0/130 (0%) 0 0/89 (0%) 0 1/132 (0.8%) 1 0/90 (0%) 0 0/360 (0%) 0
    Fracture pain 0/130 (0%) 0 1/89 (1.1%) 1 0/132 (0%) 0 0/90 (0%) 0 0/360 (0%) 0
    Lumbar spinal stenosis 0/130 (0%) 0 0/89 (0%) 0 0/132 (0%) 0 1/90 (1.1%) 1 0/360 (0%) 0
    Osteoarthritis 1/130 (0.8%) 1 0/89 (0%) 0 1/132 (0.8%) 1 0/90 (0%) 0 0/360 (0%) 0
    Rhabdomyolysis 0/130 (0%) 0 1/89 (1.1%) 1 0/132 (0%) 0 0/90 (0%) 0 1/360 (0.3%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma 0/130 (0%) 0 0/89 (0%) 0 0/132 (0%) 0 0/90 (0%) 0 1/360 (0.3%) 1
    Benign pancreatic neoplasm 1/130 (0.8%) 1 0/89 (0%) 0 0/132 (0%) 0 0/90 (0%) 0 0/360 (0%) 0
    Bladder transitional cell carcinoma 0/130 (0%) 0 0/89 (0%) 0 0/132 (0%) 0 0/90 (0%) 0 1/360 (0.3%) 1
    Chronic lymphocytic leukaemia 0/130 (0%) 0 0/89 (0%) 0 0/132 (0%) 0 1/90 (1.1%) 1 0/360 (0%) 0
    Colorectal cancer 0/130 (0%) 0 0/89 (0%) 0 0/132 (0%) 0 1/90 (1.1%) 1 0/360 (0%) 0
    Malignant melanoma 0/130 (0%) 0 0/89 (0%) 0 0/132 (0%) 0 0/90 (0%) 0 1/360 (0.3%) 1
    Prostate cancer 1/130 (0.8%) 1 0/89 (0%) 0 0/132 (0%) 0 0/90 (0%) 0 0/360 (0%) 0
    Renal cancer 0/130 (0%) 0 0/89 (0%) 0 0/132 (0%) 0 1/90 (1.1%) 1 0/360 (0%) 0
    Nervous system disorders
    Amnesia 0/130 (0%) 0 0/89 (0%) 0 0/132 (0%) 0 0/90 (0%) 0 1/360 (0.3%) 1
    Cluster headache 0/130 (0%) 0 0/89 (0%) 0 1/132 (0.8%) 1 0/90 (0%) 0 0/360 (0%) 0
    Coma 0/130 (0%) 0 0/89 (0%) 0 0/132 (0%) 0 0/90 (0%) 0 1/360 (0.3%) 1
    Encephalopathy 0/130 (0%) 0 0/89 (0%) 0 1/132 (0.8%) 1 0/90 (0%) 0 0/360 (0%) 0
    Ischaemic stroke 1/130 (0.8%) 1 0/89 (0%) 0 0/132 (0%) 0 0/90 (0%) 0 0/360 (0%) 0
    Post-traumatic headache 0/130 (0%) 0 0/89 (0%) 0 1/132 (0.8%) 1 0/90 (0%) 0 0/360 (0%) 0
    Sciatica 0/130 (0%) 0 0/89 (0%) 0 0/132 (0%) 0 1/90 (1.1%) 1 0/360 (0%) 0
    Syncope 0/130 (0%) 0 1/89 (1.1%) 1 2/132 (1.5%) 2 0/90 (0%) 0 0/360 (0%) 0
    Toxic encephalopathy 0/130 (0%) 0 0/89 (0%) 0 1/132 (0.8%) 1 0/90 (0%) 0 0/360 (0%) 0
    Psychiatric disorders
    Aggression 0/130 (0%) 0 1/89 (1.1%) 1 0/132 (0%) 0 1/90 (1.1%) 1 0/360 (0%) 0
    Agitation 0/130 (0%) 0 1/89 (1.1%) 1 0/132 (0%) 0 2/90 (2.2%) 2 0/360 (0%) 0
    Confusional state 0/130 (0%) 0 0/89 (0%) 0 0/132 (0%) 0 0/90 (0%) 0 1/360 (0.3%) 1
    Delirium 0/130 (0%) 0 0/89 (0%) 0 1/132 (0.8%) 1 0/90 (0%) 0 0/360 (0%) 0
    Major depression 0/130 (0%) 0 0/89 (0%) 0 1/132 (0.8%) 1 0/90 (0%) 0 0/360 (0%) 0
    Mental status changes 0/130 (0%) 0 0/89 (0%) 0 1/132 (0.8%) 1 1/90 (1.1%) 1 0/360 (0%) 0
    Paranoia 0/130 (0%) 0 0/89 (0%) 0 1/132 (0.8%) 1 0/90 (0%) 0 0/360 (0%) 0
    Persecutory delusion 0/130 (0%) 0 0/89 (0%) 0 0/132 (0%) 0 1/90 (1.1%) 1 0/360 (0%) 0
    Suicide attempt 1/130 (0.8%) 1 0/89 (0%) 0 0/132 (0%) 0 0/90 (0%) 0 0/360 (0%) 0
    Renal and urinary disorders
    Calculus urinary 0/130 (0%) 0 0/89 (0%) 0 1/132 (0.8%) 1 0/90 (0%) 0 0/360 (0%) 0
    Urinary bladder polyp 0/130 (0%) 0 1/89 (1.1%) 1 0/132 (0%) 0 0/90 (0%) 0 0/360 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 1/130 (0.8%) 1 0/89 (0%) 0 0/132 (0%) 0 0/90 (0%) 0 0/360 (0%) 0
    Chronic obstructive pulmonary disease 1/130 (0.8%) 1 0/89 (0%) 0 0/132 (0%) 0 0/90 (0%) 0 0/360 (0%) 0
    Hypoxia 0/130 (0%) 0 0/89 (0%) 0 1/132 (0.8%) 1 0/90 (0%) 0 0/360 (0%) 0
    Pulmonary embolism 0/130 (0%) 0 0/89 (0%) 0 0/132 (0%) 0 0/90 (0%) 0 1/360 (0.3%) 1
    Tonsillar cyst 0/130 (0%) 0 0/89 (0%) 0 1/132 (0.8%) 1 0/90 (0%) 0 0/360 (0%) 0
    Vascular disorders
    Deep vein thrombosis 0/130 (0%) 0 0/89 (0%) 0 1/132 (0.8%) 1 0/90 (0%) 0 1/360 (0.3%) 1
    Other (Not Including Serious) Adverse Events
    Placebo Double Blind Period Dose 1 Semorinemab Double Blind Period Dose 2 Semorinemab Double Blind Period Dose 3 Semorinemab Double Blind Period Dose 2 Semorinemab Open Label
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 76/130 (58.5%) 57/89 (64%) 88/132 (66.7%) 60/90 (66.7%) 76/360 (21.1%)
    Gastrointestinal disorders
    Diarrhoea 4/130 (3.1%) 4 5/89 (5.6%) 7 10/132 (7.6%) 11 4/90 (4.4%) 4 5/360 (1.4%) 6
    Nausea 0/130 (0%) 0 9/89 (10.1%) 9 8/132 (6.1%) 9 4/90 (4.4%) 5 3/360 (0.8%) 4
    General disorders
    Fatigue 2/130 (1.5%) 2 1/89 (1.1%) 1 4/132 (3%) 5 5/90 (5.6%) 5 1/360 (0.3%) 3
    Infections and infestations
    Nasopharyngitis 11/130 (8.5%) 15 5/89 (5.6%) 6 18/132 (13.6%) 24 12/90 (13.3%) 14 2/360 (0.6%) 2
    Upper respiratory tract infection 15/130 (11.5%) 21 6/89 (6.7%) 8 7/132 (5.3%) 8 5/90 (5.6%) 6 4/360 (1.1%) 4
    Urinary tract infection 10/130 (7.7%) 13 4/89 (4.5%) 4 10/132 (7.6%) 11 5/90 (5.6%) 8 10/360 (2.8%) 11
    Injury, poisoning and procedural complications
    Fall 22/130 (16.9%) 26 14/89 (15.7%) 15 22/132 (16.7%) 33 7/90 (7.8%) 11 18/360 (5%) 21
    Infusion related reaction 6/130 (4.6%) 6 10/89 (11.2%) 16 11/132 (8.3%) 15 6/90 (6.7%) 11 5/360 (1.4%) 5
    Skin laceration 4/130 (3.1%) 4 6/89 (6.7%) 6 2/132 (1.5%) 2 0/90 (0%) 0 5/360 (1.4%) 5
    Investigations
    Blood pressure increased 2/130 (1.5%) 2 1/89 (1.1%) 1 8/132 (6.1%) 12 2/90 (2.2%) 3 3/360 (0.8%) 3
    Musculoskeletal and connective tissue disorders
    Arthralgia 8/130 (6.2%) 10 6/89 (6.7%) 7 10/132 (7.6%) 12 8/90 (8.9%) 8 8/360 (2.2%) 8
    Back pain 8/130 (6.2%) 8 5/89 (5.6%) 5 8/132 (6.1%) 8 6/90 (6.7%) 7 5/360 (1.4%) 5
    Nervous system disorders
    Dizziness 12/130 (9.2%) 12 5/89 (5.6%) 7 6/132 (4.5%) 7 7/90 (7.8%) 9 4/360 (1.1%) 4
    Headache 10/130 (7.7%) 13 2/89 (2.2%) 2 8/132 (6.1%) 11 6/90 (6.7%) 9 15/360 (4.2%) 15
    Psychiatric disorders
    Anxiety 3/130 (2.3%) 3 10/89 (11.2%) 10 6/132 (4.5%) 7 6/90 (6.7%) 6 1/360 (0.3%) 1
    Depression 5/130 (3.8%) 5 5/89 (5.6%) 5 7/132 (5.3%) 8 5/90 (5.6%) 6 3/360 (0.8%) 3
    Insomnia 3/130 (2.3%) 3 2/89 (2.2%) 2 4/132 (3%) 4 5/90 (5.6%) 5 2/360 (0.6%) 2
    Respiratory, thoracic and mediastinal disorders
    Cough 4/130 (3.1%) 4 6/89 (6.7%) 6 7/132 (5.3%) 7 5/90 (5.6%) 8 5/360 (1.4%) 5
    Vascular disorders
    Hypertension 7/130 (5.4%) 7 4/89 (4.5%) 4 14/132 (10.6%) 14 5/90 (5.6%) 6 4/360 (1.1%) 5

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    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/Title Medical Communications
    Organization Hoffmann-La Roche
    Phone 800-821-8590
    Email genentech@druginfo.com
    Responsible Party:
    Genentech, Inc.
    ClinicalTrials.gov Identifier:
    NCT03289143
    Other Study ID Numbers:
    • GN39763
    • 2017-001800-31
    First Posted:
    Sep 20, 2017
    Last Update Posted:
    Mar 16, 2022
    Last Verified:
    Feb 1, 2022