Clincosm LogoSign in Get a demo

A Long-Term Safety Extension of Studies ABE4869g and ABE4955g in Participants With Mild to Moderate Alzheimer's Disease Treated With Crenezumab

Sponsor
Genentech, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01723826
Collaborator
(none)
360
Enrollment
86
Locations
1
Arm
50.1
Actual Duration (Months)
4.2
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This Phase II, open-label extension (OLE), multicenter study will evaluate the long-term safety and tolerability of crenezumab in participants with mild to moderate Alzheimer's disease who have participated in and completed the treatment period of the Phase II Study ABE4869g (NCT01343966) or ABE4955g (NCT01397578). Participants who received placebo in Study ABE4869g (NCT01343966) or ABE4955g (NCT01397578) will receive crenezumab. Anticipated time on study treatment is 144 weeks.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
360 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Open-Label, Long-Term Safety Extension of Phase II Studies ABE4869g and ABE4955g in Patients With Mild to Moderate Alzheimer's Disease
Actual Study Start Date :
Dec 7, 2012
Actual Primary Completion Date :
Feb 8, 2017
Actual Study Completion Date :
Feb 8, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: Crenezumab

Participants will receive intravenous infusion of crenezumab every 4 weeks for 144 weeks.

Drug: Crenezumab
Participants will receive intravenous infusion of crenezumab every 4 weeks for 144 weeks.
Other Names:
  • RO5490245

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants With Adverse Events (AEs) [Up to 50 months]

      An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product which does not necessarily 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.

    2. Percentage of Participants by Nature of AEs [Up to 50 months]

      A serious adverse event (SAE) is any AE that meets any of the following criteria: fatal, life threatening, requires or prolongs inpatient hospitalization, results in persistent or significant disability/incapacity, congenital anomaly/birth defect in a neonate/infant. Non-SAE of special interest for this study include the following: cerebral vascular edema, Superficial siderosis of central nervous system, cerebral micro-hemorrhages or macro-hemorrhages, pneumonia, liver injury.

    3. Percentage of Participants by Severity of AEs [Up to 50 months]

      AE severity grading scale for the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 was used for assessing adverse event severity. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on the following general guideline: Grade 1) mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated, Grade 2) moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL), Grade 3) severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL, Grade 4) life-threatening consequences; urgent intervention indicated, Grade 5) death related to AE.

    4. Percentage of Participants With Human Anti-Therapeutic Antibody (ATA) Formation [Pre-dose (Day-14), predose at Week 25, 49, 97, Follow-up Week 8 (Week 153) and 12 (Week 157)]

      ATA is a measurement to explore the potential relationship of immunogenicity response with pharmacokinetics, safety and efficacy. Percentage of participants at post-baseline with positive results for ATA against crenezumab are reported.

    5. Percentage of Participants With Amyloid-Related Imaging Abnormalities Edema/Effusions (ARIA-E) [Baseline, Weeks 23, 47, 71, 97, 121 and 153]

      Alzheimer's disease (AD) is associated with ARIA. The occurrence of imaging abnormalities believed to represent cerebral vasogenic edema, has been reported in association with the investigational use of compounds that are intended to treat Alzheimer's disease by reducing Abeta in the brain. Here, the percentage of participants with symptomatic and asymptomatic ARIA-E were reported.

    6. Percentage of Participants With Amyloid-Related Imaging Abnormalities-Hemorrhage (ARIA-H) [Baseline, Weeks 23, 47, 71, 97, 121 and 153]

      AD is associated with ARIA. Cerebral micro-hemorrhages (microbleeds [MBs]) are radiologically defined as small dot-like foci of signal loss observed on magnetic resonance imaging (MRI) sequences sensitive for paramagnetic tissue properties. The occurrence of MBs has also been identified as an adverse event in anti-amyloid vaccination trials, and together with superficial siderosis, they have been termed ARIA-H.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    50 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Previous participation in Study ABE4869g or ABE4955g and completion of the Week 73 visit

    • Adequate visual and auditory acuity, in the investigator's judgment, to allow for neuropsychological testing

    • Availability of a person ("caregiver") who can provide information on activities of daily living and behavior in order to complete the study-specific assessments

    • Diagnosis of probable Alzheimer's disease according to the National Institute on Neurological and Communication Disease and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria (McKhann et al. 1984)

    • Mini-Mental State Examination (MMSE) score of 10 or more at screening (Folstein et al.

    • For male participants with partners with reproductive potential, agreement to use a reliable means of contraception (e.g., condoms) during the study and for at least 8 weeks following the last dose of study drug

    • For female participants, a negative pregnancy test at screening

    Exclusion Criteria:

    • Early treatment and/or study discontinuation prior to completion of the Week 73 visit of Genentech Study ABE4869g or ABE4955g

    • Early discontinuation from the treatment schedule of a prior version of Study GN28525 for safety reasons. If treatment discontinuation occurred for safety reasons, participants may not re-start dosing on extended treatment schedules offered in amendments to Study GN28525

    • Inability to tolerate Magnetic Resonance Imaging (MRI) procedures or contraindication to MRI

    • Female participants with reproductive potential: Female participants must either have undergone documented surgical sterilization or have not experienced menstruation for at least 12 consecutive months

    • Severe or unstable medical condition that, in the opinion of the investigator or Sponsor, would interfere with the participant's ability to complete the study assessments or would require the equivalent of institutional or hospital care

    • History or presence of clinically evident vascular disease potentially affecting the brain

    • History of severe, clinically significant central nervous system trauma

    • History or presence of clinically relevant intracranial tumor

    • Presence of infections that affect the brain function or history of infections that resulted in neurologic sequelae

    • History or presence of systemic autoimmune disorders potentially causing progressive neurologic disease

    • History or presence of a neurologic disease other than Alzheimer's disease that may affect cognition

    • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins

    • Evidence of malignancies (except squamous cell cancer or basal cell cancer of the skin), acute infections, renal failure that requires dialysis, or other unstable medical disease not related to Alzheimer's disease that, in the investigator's opinion, would preclude participant's participation. Cancer that is not being actively treated with anti-cancer therapy or radiotherapy as well as cancers which are considered to have low probability of recurrence are allowed

    • History or presence of atrial fibrillation that, in the investigator's judgment, poses a risk for future stroke

    • Chronic kidney disease of Stage greater than or equal to (>=) 4, according to the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI) guidelines for chronic kidney disease (CKD)

    • Impaired hepatic function

    • Impaired coagulation (activated partial thromboplastin time [aPTT] greater than [>] 1.2 times upper limit of normal [ULN])

    • Platelet count less than (<) 100,000 per microliter (mcL)

    • Presence at screening of superficial siderosis of central nervous system, more than 8 cerebral microhemorrhages, or evidence of a prior cerebral macrohemorrhage

    • Presence at screening of any other significant cerebral abnormalities, including ARIA-E

    • Treatment with anticoagulation medications within 2 weeks prior to enrollment. Clopidogrel, dipyridamole, and aspirin are permitted

    • Treatment with anticholinergic antidepressants, typical antipsychotics, or barbiturates within 2 weeks prior to enrollment. All other antidepressants and atypical antipsychotics are allowed with certain restrictions as defined in the protocol

    • Chronic use of opiates, opioids, or benzodiazepines

    • Any biologic therapy within 75 weeks prior to enrollment

    • Any investigational agent (other than crenezumab) within 75 weeks prior to enrollment

    • Treatment with anticholinergic antidepressants, typical antipsychotics, barbiturates, or narcotics within 5 half-lives or 3 months prior to screening, whichever is longer. All other antidepressants and atypical antipsychotics are allowed. Chronic use of benzodiazepines is not allowed; however, the intermittent use of benzodiazepines is allowed, except within 2 days prior to any neurocognitive assessment

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Banner Alzheimer's Institute Phoenix Arizona United States 85006
    2 Mayo Clinic Scottsdale Arizona United States 85259
    3 Banner Sun Health Research Insitute Sun City Arizona United States 85351
    4 Pharmacology Research Inst Encino California United States 91316
    5 Margolin Brain Institute Fresno California United States 93720
    6 Univ of CA San Diego; Neurosciences Comp.Alzheimer's La Jolla California United States 92037
    7 USC School of Medicine Los Angeles California United States 90033
    8 University of California Los Angeles (UCLA) Los Angeles California United States 90095
    9 Pharmacology Research Inst Newport Beach California United States 92660
    10 Pacific Neuroscience Med Grp Oxnard California United States 93030
    11 Stanford Univ Medical Center Palo Alto California United States 94304
    12 University of California Davis Medical System Sacramento California United States 95817
    13 Pacific Research Network - PRN San Diego California United States 92103
    14 Uni of California San Francisco San Francisco California United States 94117
    15 Redwood Regional Medical Group Santa Rosa California United States 95403
    16 Yale University New Haven Connecticut United States 06511
    17 Florida Atlantic University; College of Medicine Boca Raton Florida United States 33431
    18 Meridien Research Brooksville Florida United States 34601
    19 Brain Matters Research, Inc. Delray Beach Florida United States 33445
    20 Miami Jewish Health Systems; Clinical Research Miami Florida United States 33137
    21 Collier Neurologic Specialists Naples Florida United States 34105
    22 Bioclinica Research Orlando Florida United States 32806
    23 Axiom Clinical Research of Florida Tampa Florida United States 33609
    24 Premiere Research Institute West Palm Beach Florida United States 33407
    25 Dekalb Neurology Associates Decatur Georgia United States 30033
    26 Rush Alzheimer's Disease Cntr. Chicago Illinois United States 60612
    27 Alexian Brothers Neurosci Inst Elk Grove Village Illinois United States 60007
    28 Indiana Univ School of Med Indianapolis Indiana United States 46202
    29 Louisiana Research Associates New Orleans Louisiana United States 70114
    30 Hattiesburg Clinic Hattiesburg Mississippi United States 39401
    31 Millennium Psychiatric Associates, LLC Saint Louis Missouri United States 63132
    32 Cleveland Clinic Lou Ruvo; Center for Brain Research Las Vegas Nevada United States 89106
    33 Memory Enhancement Center of America, Inc. Eatontown New Jersey United States 07724
    34 NeuroCognitive Institute Mount Arlington New Jersey United States 07856
    35 Empire Neurology, PC Latham New York United States 12210
    36 Litwin Zucker Research Ctr.; Feinstein Inst. Med. Rsch. Manhasset New York United States 11030
    37 Columbia University Medical Center New York New York United States 10032
    38 University of Rochester Medical Center; Monroe Community Hospital Rochester New York United States 14627
    39 Investigational Drug Service; Univ of Rochester Medical Ctr Rochester New York United States 14642
    40 Raleigh Neurology Associates Raleigh North Carolina United States 27607-6520
    41 Summit Research Network Inc. Portland Oregon United States 97210
    42 The Clinical Trial Center, LLC Jenkintown Pennsylvania United States 19046
    43 Rhode Island Mood & Memory Research Institute East Providence Rhode Island United States 02914
    44 Butler Hospital Providence Rhode Island United States 02906
    45 Medical Uni of South Carolina North Charleston South Carolina United States 29425
    46 Alzheimers Disease & Memory Disorders Center; Department of Neurology Baylor College of Medicine Houston Texas United States 77030
    47 Clinical Neuroscience Research Associates, Inc. Bennington Vermont United States 05201
    48 The Med Arts Health Rsrch Grp Kelowna British Columbia Canada V1Y 3G8
    49 University of British Columbia Hospital; Division of Neurology Vancouver British Columbia Canada V6T 2B5
    50 Capitol District Health Authority Halilfax Nova Scotia Canada B3H 2E1
    51 Jbn Medical Diagnostic Services Inc. Burlington Ontario Canada L7M 4Y1
    52 Hotel Dieu Hospital Kingston Ontario Canada K7L 2V7
    53 St. Joseph's HC-Parkwood Hosp London Ontario Canada N6C 5J1
    54 Bruyere Continuing Care Ottawa Ontario Canada K1N 5C8
    55 Kawartha Centre - Redefining Healthy Aging Peterborough Ontario Canada K9H 2P4
    56 Toronto Memory Program (Neurology Research Inc.) Toronto Ontario Canada M3B 2S7
    57 Clinique Neuro Rive-Sud Greenfield Park Quebec Canada J4V 2J2
    58 Hôpital Maisonneuve-Rosemont/Polyclinique;Recherche Clinique Montreal Quebec Canada H1T 2M4
    59 CHAUQ Hopital Enfant-Jesus Quebec City Quebec Canada G1J 1Z4
    60 McGill Univeristy; Douglas Mental Health University Institute; Neurological and Psychiatric Verdun Quebec Canada H4H 1R3
    61 Hopital neurologique Pierre Wertheimer - CHU Lyon; Neurologie Bron France 69677
    62 CHU de Limoges Hopital Dupuytren; Service de Medecine Geriatrique Limoges France 87042
    63 Hopital Central; Neurologie Nancy France 54035
    64 Hopital Nord Laennec Nantes France 44093
    65 CHU de Rouen Hopital; Service de Neurologie Rouen France 76031
    66 Hôpital Civil de Strasbourg Strasbourg France 67091
    67 Univ Berlin; Klin fur Psychi & Psycho Charite Berlin Germany 12203
    68 Bezirkskrankenhaus Günzburg Günzburg Germany 89312
    69 Zentralinstitut fuer Seelische Gesundheit Mannheim Germany 68159
    70 Ludwig-Maximilians-Univ. Munchen Germany 81377
    71 Klinikum rechts der Isar der Technischen Universität München Munchen Germany 81675
    72 Universitätsklinik Tübingen; Psychiatrie und Psychotherapie Tubingen Germany 72076
    73 Fundació ACE BArcelon Barcelona Spain 08034
    74 Hospital General de Catalunya San Cugat Del Valles Barcelona Spain 08195
    75 Policlinica Guipuzcoa San Sebastian Guipuzcoa Spain 20009
    76 Hospital de Cruces; Servicio de Neurologia Barakaldo Vizcaya Spain 48903
    77 Complejo Hospitalario Universitario de Albacete Albacete Spain 2006
    78 Clinica Ruber, 4 planta; Servicio de Neurologia Madrid Spain 28006
    79 The Rice Centre; Royal United Hospital Bath United Kingdom BA1 3NG
    80 West London Research Unit; Brentford Lodge Brentford United Kingdom TW8 8DS
    81 Royal Sussex County Hospital, CIRU Level 5 Brighton United Kingdom BN2 5BE
    82 Glasgow Memory Clinic Glasgow United Kingdom G20 0XA
    83 The National Hospital for Neurology & Neurosurgery; Dementia Research Center London, GT LON United Kingdom WC1N 3BG
    84 Southampton General Hospital; Pharmacy Southampton United Kingdom SO16 6YD
    85 Moorgreen Hospital; Memory Assessment & Rsch Ctr Southampton United Kingdom SO30 3JB
    86 Great Western Hosp.; Kingshill Research Ctr Swindon United Kingdom SN3 6BW

    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:
    NCT01723826
    Other Study ID Numbers:
    • GN28525
    • 2012-003242-33
    First Posted:
    Nov 8, 2012
    Last Update Posted:
    Feb 20, 2020
    Last Verified:
    Feb 1, 2020
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Alzheimer Disease

    Study Results

    Participant Flow

    Recruitment Details A total of 360 participants were enrolled at 83 sites across 6 countries.
    Pre-assignment Detail Participants who completed either Phase II Study NCT01343966 (ABE4869g) or NCT01397578 (ABE4955g) and had Mini-Mental State Examination (MMSE) score of 10 or more at the time of screening were included. Participant flow is represented based on the safety population by treatment received.
    Arm/Group Title PCP PL - OLE CREN SC - OLE CREN IV PCP PL - OLE CREN IV PCP CREN SC - OLE CREN SC - OLE CREN IV PCP CREN IV - OLE CREN IV
    Arm/Group Description Participants who on their placebo-controlled portion [PCP]/parent study received placebo (PL) and who on this open-label extension (OLE) study initially received crenezumab (CREN) subcutaneously (SC) and after the protocol amendment received CREN intravenously (IV). Participants who on their PCP/parent study received placebo and who on this OLE study received CREN IV. Participants who on their PCP/parent study received CREN and who on this OLE study initially received CREN SC and after the protocol amendment received CREN IV. Participants who on their PCP/parent study received CREN IV and who on this OLE study received CREN IV.
    Period Title: Overall Study
    STARTED 47 63 101 149
    COMPLETED 20 27 44 59
    NOT COMPLETED 27 36 57 90

    Baseline Characteristics

    Arm/Group Title PCP PL - OLE CREN SC - OLE CREN IV PCP PL - OLE CREN IV PCP CREN SC - OLE CREN SC - OLE CREN IV PCP CREN IV - OLE CREN IV Total
    Arm/Group Description Participants who on their placebo-controlled portion [PCP]/parent study received placebo (PL) and who on this open-label extension (OLE) study initially received crenezumab (CREN) subcutaneously (SC) and after the protocol amendment received CREN intravenously (IV). Participants who on their PCP/parent study received placebo and who on this OLE study received CREN IV. Participants who on their PCP/parent study received CREN and who on this OLE study initially received CREN SC and after the protocol amendment received CREN IV. Participants who on their PCP/parent study received CREN IV and who on this OLE study received CREN IV. Total of all reporting groups
    Overall Participants 47 63 101 149 360
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    70.9
    (7.4)
    71.9
    (7.4)
    72.3
    (7.2)
    72.2
    (6.7)
    72.0
    (7.0)
    Sex: Female, Male (Count of Participants)
    Female
    26
    55.3%
    36
    57.1%
    58
    57.4%
    79
    53%
    199
    55.3%
    Male
    21
    44.7%
    27
    42.9%
    43
    42.6%
    70
    47%
    161
    44.7%
    Race/Ethnicity, Customized (Count of Participants)
    Hispanic or Latino
    2
    4.3%
    2
    3.2%
    2
    2%
    4
    2.7%
    10
    2.8%
    Not Hispanic or Latino
    45
    95.7%
    61
    96.8%
    98
    97%
    145
    97.3%
    349
    96.9%
    Not Stated
    0
    0%
    0
    0%
    1
    1%
    0
    0%
    1
    0.3%
    Race/Ethnicity, Customized (Count of Participants)
    Asian
    0
    0%
    0
    0%
    0
    0%
    4
    2.7%
    4
    1.1%
    Black or African American
    0
    0%
    0
    0%
    4
    4%
    1
    0.7%
    5
    1.4%
    White
    47
    100%
    63
    100%
    97
    96%
    144
    96.6%
    351
    97.5%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants With Adverse Events (AEs)
    Description An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product which does not necessarily 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 50 months

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis population included all participants who received at least one dose of study drug.
    Arm/Group Title PCP PL - OLE CREN SC - OLE CREN IV PCP PL - OLE CREN IV PCP CREN - OLE CREN SC -OLE CREN IV PCP CREN - OLE CREN IV
    Arm/Group Description Participants who on their placebo-controlled portion [PCP]/parent study received placebo (PL) and who on this open-label extension (OLE) study initially received crenezumab (CREN) subcutaneously (SC) and after the protocol amendment received CREN intravenously (IV). Participants who on their PCP/parent study received placebo and who on this OLE study received CREN IV. Participants who on their PCP/parent study received CREN and who on this OLE study initially received CREN SC and after the protocol amendment received CREN IV. Participants who on their PCP/parent study received CREN IV and who on this OLE study received CREN IV.
    Measure Participants 47 63 101 149
    Number [percentage of participants]
    89.4
    190.2%
    90.5
    143.7%
    96.0
    95%
    87.9
    59%
    2. Primary Outcome
    Title Percentage of Participants by Nature of AEs
    Description A serious adverse event (SAE) is any AE that meets any of the following criteria: fatal, life threatening, requires or prolongs inpatient hospitalization, results in persistent or significant disability/incapacity, congenital anomaly/birth defect in a neonate/infant. Non-SAE of special interest for this study include the following: cerebral vascular edema, Superficial siderosis of central nervous system, cerebral micro-hemorrhages or macro-hemorrhages, pneumonia, liver injury.
    Time Frame Up to 50 months

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis population included all participants who received at least one dose of study drug.
    Arm/Group Title PCP PL - OLE CREN SC - OLE CREN IV PCP PL - OLE CREN IV PCP CREN - OLE CREN SC -OLE CREN IV PCP CREN - OLE CREN IV
    Arm/Group Description Participants who on their placebo-controlled portion [PCP]/parent study received placebo (PL) and who on this open-label extension (OLE) study initially received crenezumab (CREN) subcutaneously (SC) and after the protocol amendment received CREN intravenously (IV). Participants who on their PCP/parent study received placebo and who on this OLE study received CREN IV. Participants who on their PCP/parent study received CREN and who on this OLE study initially received CREN SC and after the protocol amendment received CREN IV. Participants who on their PCP/parent study received CREN IV and who on this OLE study received CREN IV.
    Measure Participants 47 63 101 149
    SAE
    19.1
    40.6%
    22.2
    35.2%
    21.8
    21.6%
    23.5
    15.8%
    Non-SAE
    87.2
    185.5%
    88.9
    141.1%
    94.1
    93.2%
    87.2
    58.5%
    3. Primary Outcome
    Title Percentage of Participants by Severity of AEs
    Description AE severity grading scale for the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 was used for assessing adverse event severity. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on the following general guideline: Grade 1) mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated, Grade 2) moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL), Grade 3) severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL, Grade 4) life-threatening consequences; urgent intervention indicated, Grade 5) death related to AE.
    Time Frame Up to 50 months

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis population included all participants who received at least one dose of study drug.
    Arm/Group Title PCP PL - OLE CREN SC - OLE CREN IV PCP PL - OLE CREN IV PCP CREN - OLE CREN SC -OLE CREN IV PCP CREN - OLE CREN IV
    Arm/Group Description Participants who on their placebo-controlled portion [PCP]/parent study received placebo (PL) and who on this open-label extension (OLE) study initially received crenezumab (CREN) subcutaneously (SC) and after the protocol amendment received CREN intravenously (IV). Participants who on their PCP/parent study received placebo and who on this OLE study received CREN IV. Participants who on their PCP/parent study received CREN and who on this OLE study initially received CREN SC and after the protocol amendment received CREN IV. Participants who on their PCP/parent study received CREN IV and who on this OLE study received CREN IV.
    Measure Participants 47 63 101 149
    Grade 1
    19.1
    40.6%
    34.9
    55.4%
    29.7
    29.4%
    22.1
    14.8%
    Grade 2
    44.7
    95.1%
    31.7
    50.3%
    43.6
    43.2%
    40.3
    27%
    Grade 3
    12.8
    27.2%
    17.5
    27.8%
    16.8
    16.6%
    19.5
    13.1%
    Grade 4
    8.5
    18.1%
    1.6
    2.5%
    3.0
    3%
    1.3
    0.9%
    Grade 5
    4.3
    9.1%
    4.8
    7.6%
    3.0
    3%
    4.7
    3.2%
    4. Primary Outcome
    Title Percentage of Participants With Human Anti-Therapeutic Antibody (ATA) Formation
    Description ATA is a measurement to explore the potential relationship of immunogenicity response with pharmacokinetics, safety and efficacy. Percentage of participants at post-baseline with positive results for ATA against crenezumab are reported.
    Time Frame Pre-dose (Day-14), predose at Week 25, 49, 97, Follow-up Week 8 (Week 153) and 12 (Week 157)

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis population included all participants who received at least one dose of study drug.
    Arm/Group Title PCP PL - OLE CREN SC - OLE CREN IV PCP PL - OLE CREN IV PCP CREN - OLE CREN SC -OLE CREN IV PCP CREN - OLE CREN IV
    Arm/Group Description Participants who on their placebo-controlled portion [PCP]/parent study received placebo (PL) and who on this open-label extension (OLE) study initially received crenezumab (CREN) subcutaneously (SC) and after the protocol amendment received CREN intravenously (IV). Participants who on their PCP/parent study received placebo and who on this OLE study received CREN IV. Participants who on their PCP/parent study received CREN and who on this OLE study initially received CREN SC and after the protocol amendment received CREN IV. Participants who on their PCP/parent study received CREN IV and who on this OLE study received CREN IV.
    Measure Participants 47 63 101 149
    Number [percentage of participants]
    9.1
    19.4%
    3.4
    5.4%
    9.1
    9%
    0.7
    0.5%
    5. Primary Outcome
    Title Percentage of Participants With Amyloid-Related Imaging Abnormalities Edema/Effusions (ARIA-E)
    Description Alzheimer's disease (AD) is associated with ARIA. The occurrence of imaging abnormalities believed to represent cerebral vasogenic edema, has been reported in association with the investigational use of compounds that are intended to treat Alzheimer's disease by reducing Abeta in the brain. Here, the percentage of participants with symptomatic and asymptomatic ARIA-E were reported.
    Time Frame Baseline, Weeks 23, 47, 71, 97, 121 and 153

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis population included all participants who received at least one dose of study drug.
    Arm/Group Title PCP PL - OLE CREN SC - OLE CREN IV PCP PL - OLE CREN IV PCP CREN - OLE CREN SC -OLE CREN IV PCP CREN - OLE CREN IV
    Arm/Group Description Participants who on their placebo-controlled portion [PCP]/parent study received placebo (PL) and who on this open-label extension (OLE) study initially received crenezumab (CREN) subcutaneously (SC) and after the protocol amendment received CREN intravenously (IV). Participants who on their PCP/parent study received placebo and who on this OLE study received CREN IV. Participants who on their PCP/parent study received CREN and who on this OLE study initially received CREN SC and after the protocol amendment received CREN IV. Participants who on their PCP/parent study received CREN IV and who on this OLE study received CREN IV.
    Measure Participants 47 63 101 149
    Symptomatic
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asymptomatic
    0
    0%
    0
    0%
    0
    0%
    0.7
    0.5%
    6. Primary Outcome
    Title Percentage of Participants With Amyloid-Related Imaging Abnormalities-Hemorrhage (ARIA-H)
    Description AD is associated with ARIA. Cerebral micro-hemorrhages (microbleeds [MBs]) are radiologically defined as small dot-like foci of signal loss observed on magnetic resonance imaging (MRI) sequences sensitive for paramagnetic tissue properties. The occurrence of MBs has also been identified as an adverse event in anti-amyloid vaccination trials, and together with superficial siderosis, they have been termed ARIA-H.
    Time Frame Baseline, Weeks 23, 47, 71, 97, 121 and 153

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis population included all participants who received at least one dose of study drug.
    Arm/Group Title PCP PL - OLE CREN SC - OLE CREN IV PCP PL - OLE CREN IV PCP CREN - OLE CREN SC -OLE CREN IV PCP CREN - OLE CREN IV
    Arm/Group Description Participants who on their placebo-controlled portion [PCP]/parent study received placebo (PL) and who on this open-label extension (OLE) study initially received crenezumab (CREN) subcutaneously (SC) and after the protocol amendment received CREN intravenously (IV). Participants who on their PCP/parent study received placebo and who on this OLE study received CREN IV. Participants who on their PCP/parent study received CREN and who on this OLE study initially received CREN SC and after the protocol amendment received CREN IV. Participants who on their PCP/parent study received CREN IV and who on this OLE study received CREN IV.
    Measure Participants 47 63 101 149
    Superficial Siderosis
    2.1
    4.5%
    0
    0%
    3.0
    3%
    0.7
    0.5%
    New Micro-hemorrhage
    6.4
    13.6%
    9.5
    15.1%
    4.0
    4%
    6.0
    4%

    Adverse Events

    Time Frame Up to 50 months
    Adverse Event Reporting Description Safety Analysis population included all participants who received at least one dose of study drug.
    Arm/Group Title PCP PL - OLE CREN SC - OLE CREN IV PCP PL - OLE CREN IV PCP CREN SC - OLE CREN SC - OLE CREN IV PCP CREN IV - OLE CREN IV
    Arm/Group Description Participants who on their placebo-controlled portion [PCP]/parent study received placebo (PL) and who on this open-label extension (OLE) study initially received crenezumab (CREN) subcutaneously (SC) and after the protocol amendment received CREN intravenously (IV). Participants who on their PCP/parent study received placebo and who on this OLE study received CREN IV. Participants who on their PCP/parent study received CREN and who on this OLE study initially received CREN SC and after the protocol amendment received CREN IV. Participants who on their PCP/parent study received CREN IV and who on this OLE study received CREN IV.
    All Cause Mortality
    PCP PL - OLE CREN SC - OLE CREN IV PCP PL - OLE CREN IV PCP CREN SC - OLE CREN SC - OLE CREN IV PCP CREN IV - OLE CREN IV
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/47 (4.3%) 3/63 (4.8%) 3/101 (3%) 7/149 (4.7%)
    Serious Adverse Events
    PCP PL - OLE CREN SC - OLE CREN IV PCP PL - OLE CREN IV PCP CREN SC - OLE CREN SC - OLE CREN IV PCP CREN IV - OLE CREN IV
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 9/47 (19.1%) 14/63 (22.2%) 22/101 (21.8%) 35/149 (23.5%)
    Blood and lymphatic system disorders
    ANAEMIA 0/47 (0%) 0 0/63 (0%) 0 1/101 (1%) 1 0/149 (0%) 0
    NEUTROPENIA 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    Cardiac disorders
    ACUTE MYOCARDIAL INFARCTION 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    ATRIAL FIBRILLATION 0/47 (0%) 0 0/63 (0%) 0 1/101 (1%) 1 1/149 (0.7%) 1
    ATRIAL FLUTTER 1/47 (2.1%) 1 0/63 (0%) 0 0/101 (0%) 0 0/149 (0%) 0
    CARDIO-RESPIRATORY ARREST 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    MYOCARDIAL INFARCTION 0/47 (0%) 0 0/63 (0%) 0 1/101 (1%) 1 2/149 (1.3%) 2
    SINUS TACHYCARDIA 0/47 (0%) 0 0/63 (0%) 0 1/101 (1%) 1 0/149 (0%) 0
    Ear and labyrinth disorders
    VERTIGO 0/47 (0%) 0 1/63 (1.6%) 1 0/101 (0%) 0 0/149 (0%) 0
    Gastrointestinal disorders
    ABDOMINAL PAIN 0/47 (0%) 0 0/63 (0%) 0 1/101 (1%) 1 1/149 (0.7%) 1
    INGUINAL HERNIA 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    INTESTINAL OBSTRUCTION 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    NAUSEA 0/47 (0%) 0 0/63 (0%) 0 1/101 (1%) 1 0/149 (0%) 0
    SMALL INTESTINAL OBSTRUCTION 0/47 (0%) 0 0/63 (0%) 0 1/101 (1%) 1 0/149 (0%) 0
    VOMITING 0/47 (0%) 0 0/63 (0%) 0 1/101 (1%) 1 0/149 (0%) 0
    General disorders
    ASTHENIA 0/47 (0%) 0 0/63 (0%) 0 1/101 (1%) 1 0/149 (0%) 0
    CHEST PAIN 0/47 (0%) 0 0/63 (0%) 0 1/101 (1%) 1 2/149 (1.3%) 2
    DEATH 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    GAIT DISTURBANCE 0/47 (0%) 0 0/63 (0%) 0 1/101 (1%) 1 1/149 (0.7%) 1
    INCARCERATED HERNIA 0/47 (0%) 0 0/63 (0%) 0 1/101 (1%) 1 0/149 (0%) 0
    Hepatobiliary disorders
    BILIARY COLIC 1/47 (2.1%) 1 0/63 (0%) 0 0/101 (0%) 0 0/149 (0%) 0
    CHOLELITHIASIS 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    Infections and infestations
    BACTERAEMIA 1/47 (2.1%) 1 0/63 (0%) 0 0/101 (0%) 0 0/149 (0%) 0
    DIVERTICULITIS 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    ESCHERICHIA URINARY TRACT INFECTION 0/47 (0%) 0 0/63 (0%) 0 2/101 (2%) 2 0/149 (0%) 0
    GASTROENTERITIS 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    INFLUENZA 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    OSTEOMYELITIS 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    PNEUMONIA 0/47 (0%) 0 1/63 (1.6%) 1 1/101 (1%) 1 3/149 (2%) 5
    PNEUMONIA BACTERIAL 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    PNEUMONIA ESCHERICHIA 0/47 (0%) 0 0/63 (0%) 0 1/101 (1%) 1 0/149 (0%) 0
    PNEUMONIA VIRAL 0/47 (0%) 0 0/63 (0%) 0 1/101 (1%) 1 0/149 (0%) 0
    POST PROCEDURAL INFECTION 0/47 (0%) 0 0/63 (0%) 0 1/101 (1%) 1 0/149 (0%) 0
    SEPSIS 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    SEPTIC SHOCK 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    UPPER RESPIRATORY TRACT INFECTION 0/47 (0%) 0 0/63 (0%) 0 1/101 (1%) 1 0/149 (0%) 0
    URINARY TRACT INFECTION 0/47 (0%) 0 0/63 (0%) 0 2/101 (2%) 2 1/149 (0.7%) 1
    UROSEPSIS 0/47 (0%) 0 1/63 (1.6%) 1 0/101 (0%) 0 0/149 (0%) 0
    Injury, poisoning and procedural complications
    ANKLE FRACTURE 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    CERVICAL VERTEBRAL FRACTURE 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    FACIAL BONES FRACTURE 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    FALL 0/47 (0%) 0 1/63 (1.6%) 1 0/101 (0%) 0 1/149 (0.7%) 1
    FEMORAL NECK FRACTURE 0/47 (0%) 0 1/63 (1.6%) 1 0/101 (0%) 0 0/149 (0%) 0
    FEMUR FRACTURE 0/47 (0%) 0 1/63 (1.6%) 1 0/101 (0%) 0 0/149 (0%) 0
    FRACTURE DISPLACEMENT 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    FRACTURED SACRUM 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    HIP FRACTURE 1/47 (2.1%) 1 1/63 (1.6%) 1 1/101 (1%) 1 1/149 (0.7%) 1
    HUMERUS FRACTURE 0/47 (0%) 0 0/63 (0%) 0 1/101 (1%) 1 1/149 (0.7%) 1
    LACERATION 0/47 (0%) 0 0/63 (0%) 0 1/101 (1%) 1 0/149 (0%) 0
    LIMB INJURY 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    PELVIC FRACTURE 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    SUBARACHNOID HAEMORRHAGE 0/47 (0%) 0 1/63 (1.6%) 1 1/101 (1%) 1 0/149 (0%) 0
    SUBDURAL HAEMATOMA 2/47 (4.3%) 2 0/63 (0%) 0 0/101 (0%) 0 0/149 (0%) 0
    THORACIC VERTEBRAL FRACTURE 0/47 (0%) 0 1/63 (1.6%) 1 0/101 (0%) 0 0/149 (0%) 0
    WRIST FRACTURE 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    Metabolism and nutrition disorders
    ADULT FAILURE TO THRIVE 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    DEHYDRATION 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 3/149 (2%) 3
    Musculoskeletal and connective tissue disorders
    BACK PAIN 0/47 (0%) 0 1/63 (1.6%) 1 0/101 (0%) 0 0/149 (0%) 0
    OSTEOARTHRITIS 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    BASAL CELL CARCINOMA 0/47 (0%) 0 1/63 (1.6%) 1 0/101 (0%) 0 0/149 (0%) 0
    COLON CANCER 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    INTESTINAL ADENOCARCINOMA 0/47 (0%) 0 0/63 (0%) 0 1/101 (1%) 1 0/149 (0%) 0
    METASTATIC NEOPLASM 0/47 (0%) 0 1/63 (1.6%) 1 0/101 (0%) 0 0/149 (0%) 0
    PROSTATE CANCER 0/47 (0%) 0 1/63 (1.6%) 1 0/101 (0%) 0 0/149 (0%) 0
    Nervous system disorders
    BASILAR ARTERY STENOSIS 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    CEREBROVASCULAR ACCIDENT 0/47 (0%) 0 0/63 (0%) 0 1/101 (1%) 1 0/149 (0%) 0
    DEMENTIA 0/47 (0%) 0 2/63 (3.2%) 2 1/101 (1%) 1 0/149 (0%) 0
    DEMENTIA ALZHEIMER'S TYPE 2/47 (4.3%) 2 2/63 (3.2%) 2 0/101 (0%) 0 1/149 (0.7%) 1
    DEMENTIA WITH LEWY BODIES 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    DEPRESSED LEVEL OF CONSCIOUSNESS 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    DIZZINESS 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    ENCEPHALOPATHY 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    EPILEPSY 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    GENERALISED TONIC-CLONIC SEIZURE 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    HYDROCEPHALUS 0/47 (0%) 0 1/63 (1.6%) 1 0/101 (0%) 0 0/149 (0%) 0
    ISCHAEMIC STROKE 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    METABOLIC ENCEPHALOPATHY 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    PARAESTHESIA 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    PRESYNCOPE 0/47 (0%) 0 0/63 (0%) 0 2/101 (2%) 2 0/149 (0%) 0
    SEIZURE 0/47 (0%) 0 1/63 (1.6%) 1 0/101 (0%) 0 2/149 (1.3%) 3
    SYNCOPE 0/47 (0%) 0 2/63 (3.2%) 2 3/101 (3%) 3 0/149 (0%) 0
    TRANSIENT ISCHAEMIC ATTACK 1/47 (2.1%) 1 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    Product Issues
    DEVICE DISLOCATION 1/47 (2.1%) 1 0/63 (0%) 0 0/101 (0%) 0 0/149 (0%) 0
    DEVICE FAILURE 0/47 (0%) 0 1/63 (1.6%) 1 0/101 (0%) 0 0/149 (0%) 0
    Psychiatric disorders
    ABNORMAL BEHAVIOUR 0/47 (0%) 0 1/63 (1.6%) 1 0/101 (0%) 0 0/149 (0%) 0
    AGGRESSION 1/47 (2.1%) 1 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    AGITATION 1/47 (2.1%) 2 1/63 (1.6%) 1 1/101 (1%) 1 0/149 (0%) 0
    DELIRIUM 0/47 (0%) 0 1/63 (1.6%) 2 1/101 (1%) 1 1/149 (0.7%) 1
    DISORIENTATION 0/47 (0%) 0 0/63 (0%) 0 1/101 (1%) 1 0/149 (0%) 0
    MENTAL STATUS CHANGES 0/47 (0%) 0 0/63 (0%) 0 2/101 (2%) 2 0/149 (0%) 0
    PSYCHOTIC DISORDER 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    Renal and urinary disorders
    ACUTE PRERENAL FAILURE 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    URINARY RETENTION 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    Respiratory, thoracic and mediastinal disorders
    ACUTE RESPIRATORY FAILURE 0/47 (0%) 0 0/63 (0%) 0 1/101 (1%) 1 1/149 (0.7%) 1
    PULMONARY GRANULOMA 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    TACHYPNOEA 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    Vascular disorders
    AORTIC ANEURYSM 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    DEEP VEIN THROMBOSIS 0/47 (0%) 0 0/63 (0%) 0 1/101 (1%) 1 2/149 (1.3%) 2
    EXSANGUINATION 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    HYPERTENSION 0/47 (0%) 0 1/63 (1.6%) 1 0/101 (0%) 0 0/149 (0%) 0
    HYPOTENSION 0/47 (0%) 0 0/63 (0%) 0 2/101 (2%) 2 0/149 (0%) 0
    PHLEBITIS 0/47 (0%) 0 0/63 (0%) 0 0/101 (0%) 0 1/149 (0.7%) 1
    Other (Not Including Serious) Adverse Events
    PCP PL - OLE CREN SC - OLE CREN IV PCP PL - OLE CREN IV PCP CREN SC - OLE CREN SC - OLE CREN IV PCP CREN IV - OLE CREN IV
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 37/47 (78.7%) 51/63 (81%) 80/101 (79.2%) 97/149 (65.1%)
    Gastrointestinal disorders
    CONSTIPATION 0/47 (0%) 0 4/63 (6.3%) 4 3/101 (3%) 3 5/149 (3.4%) 5
    DIARRHOEA 6/47 (12.8%) 7 3/63 (4.8%) 3 11/101 (10.9%) 12 14/149 (9.4%) 23
    VOMITING 0/47 (0%) 0 3/63 (4.8%) 5 5/101 (5%) 6 8/149 (5.4%) 11
    General disorders
    FATIGUE 2/47 (4.3%) 2 0/63 (0%) 0 8/101 (7.9%) 8 4/149 (2.7%) 4
    INJECTION SITE ERYTHEMA 2/47 (4.3%) 13 1/63 (1.6%) 1 8/101 (7.9%) 10 2/149 (1.3%) 2
    INJECTION SITE EXTRAVASATION 3/47 (6.4%) 5 1/63 (1.6%) 1 3/101 (3%) 7 4/149 (2.7%) 16
    Infections and infestations
    BRONCHITIS 2/47 (4.3%) 2 2/63 (3.2%) 2 4/101 (4%) 5 9/149 (6%) 9
    UPPER RESPIRATORY TRACT INFECTION 6/47 (12.8%) 7 5/63 (7.9%) 5 15/101 (14.9%) 20 13/149 (8.7%) 15
    URINARY TRACT INFECTION 7/47 (14.9%) 8 9/63 (14.3%) 13 16/101 (15.8%) 23 18/149 (12.1%) 34
    VIRAL UPPER RESPIRATORY TRACT INFECTION 5/47 (10.6%) 7 11/63 (17.5%) 14 10/101 (9.9%) 11 13/149 (8.7%) 13
    Injury, poisoning and procedural complications
    CONTUSION 2/47 (4.3%) 6 2/63 (3.2%) 2 6/101 (5.9%) 8 8/149 (5.4%) 10
    FALL 7/47 (14.9%) 10 8/63 (12.7%) 11 26/101 (25.7%) 42 18/149 (12.1%) 28
    LACERATION 3/47 (6.4%) 3 2/63 (3.2%) 3 10/101 (9.9%) 11 7/149 (4.7%) 7
    SKIN ABRASION 0/47 (0%) 0 4/63 (6.3%) 4 5/101 (5%) 5 3/149 (2%) 5
    Investigations
    WEIGHT DECREASED 4/47 (8.5%) 4 2/63 (3.2%) 2 8/101 (7.9%) 11 7/149 (4.7%) 7
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA 2/47 (4.3%) 4 5/63 (7.9%) 6 8/101 (7.9%) 10 8/149 (5.4%) 10
    BACK PAIN 3/47 (6.4%) 3 4/63 (6.3%) 5 7/101 (6.9%) 7 8/149 (5.4%) 8
    MUSCLE SPASMS 3/47 (6.4%) 3 0/63 (0%) 0 4/101 (4%) 6 1/149 (0.7%) 2
    TENDONITIS 3/47 (6.4%) 3 2/63 (3.2%) 2 1/101 (1%) 1 0/149 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    SQUAMOUS CELL CARCINOMA 3/47 (6.4%) 8 1/63 (1.6%) 1 2/101 (2%) 2 0/149 (0%) 0
    Nervous system disorders
    CEREBRAL MICROHAEMORRHAGE 3/47 (6.4%) 3 4/63 (6.3%) 5 3/101 (3%) 3 6/149 (4%) 7
    DIZZINESS 2/47 (4.3%) 2 5/63 (7.9%) 5 11/101 (10.9%) 14 10/149 (6.7%) 11
    HEADACHE 1/47 (2.1%) 1 2/63 (3.2%) 2 8/101 (7.9%) 10 3/149 (2%) 4
    Psychiatric disorders
    AGITATION 9/47 (19.1%) 9 4/63 (6.3%) 4 13/101 (12.9%) 20 13/149 (8.7%) 14
    ANXIETY 1/47 (2.1%) 1 4/63 (6.3%) 4 8/101 (7.9%) 9 15/149 (10.1%) 16
    CONFUSIONAL STATE 3/47 (6.4%) 3 1/63 (1.6%) 1 3/101 (3%) 4 3/149 (2%) 4
    DELUSION 3/47 (6.4%) 3 1/63 (1.6%) 1 7/101 (6.9%) 7 4/149 (2.7%) 6
    DEPRESSION 3/47 (6.4%) 3 8/63 (12.7%) 9 5/101 (5%) 5 7/149 (4.7%) 7
    INSOMNIA 3/47 (6.4%) 6 1/63 (1.6%) 1 8/101 (7.9%) 10 8/149 (5.4%) 9
    Renal and urinary disorders
    URINARY INCONTINENCE 4/47 (8.5%) 4 0/63 (0%) 0 5/101 (5%) 6 8/149 (5.4%) 8
    Respiratory, thoracic and mediastinal disorders
    COUGH 5/47 (10.6%) 11 3/63 (4.8%) 3 8/101 (7.9%) 9 11/149 (7.4%) 13
    Skin and subcutaneous tissue disorders
    RASH 2/47 (4.3%) 7 5/63 (7.9%) 5 2/101 (2%) 2 6/149 (4%) 7
    Vascular disorders
    HAEMATOMA 3/47 (6.4%) 3 2/63 (3.2%) 2 2/101 (2%) 2 3/149 (2%) 3

    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:
    NCT01723826
    Other Study ID Numbers:
    • GN28525
    • 2012-003242-33
    First Posted:
    Nov 8, 2012
    Last Update Posted:
    Feb 20, 2020
    Last Verified:
    Feb 1, 2020