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EMERGE: 221AD302 Phase 3 Study of Aducanumab (BIIB037) in Early Alzheimer's Disease

Sponsor
Biogen (Industry)
Overall Status
Terminated
CT.gov ID
NCT02484547
Collaborator
(none)
1,643
Enrollment
180
Locations
2
Arms
46.7
Actual Duration (Months)
9.1
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of the study is to evaluate the efficacy of monthly doses of aducanumab in slowing cognitive and functional impairment as measured by changes in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score as compared with placebo in participants with early AD. Secondary objectives are to assess the effect of monthly doses of aducanumab as compared with placebo on clinical progression as measured by Mini-Mental State Examination (MMSE), AD Assessment Scale-Cognitive Subscale (13 items) [ADAS-Cog 13], and AD Cooperative Study-Activities of Daily Living Inventory (Mild Cognitive Impairment version) [ADCS-ADL-MCI].

Condition or Disease Intervention/Treatment Phase
  • Drug: Aducanumab (BIIB037)
  • Drug: Aducanumab (BIIB037)
  • Drug: Placebo
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
1643 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 3 Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Aducanumab (BIIB037) in Subjects With Early Alzheimer's Disease
Actual Study Start Date :
Sep 15, 2015
Actual Primary Completion Date :
Aug 5, 2019
Actual Study Completion Date :
Aug 5, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Low Dose

Monthly intravenous (IV) infusions

Drug: Aducanumab (BIIB037)
Low dose

Drug: Placebo
Placebo
Experimental: High Dose

Monthly intravenous (IV) infusions

Drug: Aducanumab (BIIB037)
High dose

Drug: Placebo
Placebo

Outcome Measures

Primary Outcome Measures

  1. Change From Baseline in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) Score at Week 78 [Baseline, Week 78]

    CDR-SB integrates assessments from 3 domains of cognition (memory, orientation, judgment/problem-solving) and 3 domains of function (community affairs, home/hobbies, personal care). Following caregiver interview and systematic patient examination, the rater assigns a score describing the participant's current performance level in each of these domains of life functioning. Prespecified severity anchors range from none = 0, questionable = 0.5, mild = 1, moderate = 2 to severe = 3 (the personal care domain omits the 0.5 score). "Sum of boxes" scoring methodology sums the score for each of the 6 domains and provides a value ranging from 0 to 18 that can change in increments of 0.5 or greater. Higher scores indicate greater disease severity. Mixed model for repeated measures (MMRM) analysis was used to analyze change from baseline in CDR-SB. A positive change from baseline indicates clinical decline.

Secondary Outcome Measures

  1. Change From Baseline in Mini Mental State Examination (MMSE) Score at Week 78 [Baseline, Week 78]

    The MMSE is a widely used performance-based test of global cognitive status. It consists of 11 tasks that assess orientation, word recall, attention and calculation, language abilities, and visuospatial functions. The scores from the 11 tests are combined to obtain the total score, which ranges from 0 to 30, with lower scores over time indicating increasing cognitive impairment. MMRM analysis was used to analyze change from baseline in MMSE. A negative change from baseline indicates clinical decline.

  2. Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (13 Items) (ADAS-Cog 13) at Week 78 [Baseline, Week 78]

    ADAS-Cog13 comprises both cognitive tasks and clinical ratings of cognitive performance. The scale items capture word recall, ability to follow commands, the ability to correctly copy or draw an image, naming, the ability to interact with everyday objects, orientation, word recognition, memory, comprehension of spoken language, word-finding, and language ability, with a measure for delayed word recall and concentration/distractibility. The total score ranges from 0 to 85. An increase in score over time indicates increasing cognitive impairment. MMRM analysis was used to analyze change from baseline in ADAS-Cog 13. A positive change from baseline indicates clinical decline.

  3. Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (Mild Cognitive Impairment Version) (ADCS-ADL-MCI) Score at Week 78 [Baseline, Week 78]

    The ADCS-ADL-MCI consists of 17 instrumental items (e.g., shopping, preparing meals, using household appliances) and 1 basic item (getting dressed). Ratings reflect caregiver observations about the patient's actual functioning over the previous month and provide an assessment of change in the functional state of the participant over time. The total score ranges from 0 to 53, with lower values over time reflecting functional deterioration. MMRM analysis was used to analyze change from baseline in ADAS-ADL-MCI. A negative change from baseline indicates clinical decline.

Eligibility Criteria

Criteria

Ages Eligible for Study:
50 Years to 85 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Key Inclusion Criteria:

  • Must meet all of the following clinical criteria for MCI due to AD or mild AD and must have:

  • A Clinical Dementia Rating (CDR)-Global Score of 0.5.

  • Objective evidence of cognitive impairment at screening

  • An MMSE score between 24 and 30 (inclusive)

  • Must have a positive amyloid Positron Emission Tomography (PET) scan

  • Must consent to apolipoprotein E (ApoE) genotyping

  • If using drugs to treat symptoms related to AD, doses must be stable for at least 8 weeks prior to screening visit 1

  • Must have a reliable informant or caregiver

Key Exclusion Criteria:

  • Any medical or neurological condition (other than Alzheimer's Disease) that might be a contributing cause of the subject's cognitive impairment

  • Have had a stroke or Transient Ischemic Attack (TIA) or unexplained loss of consciousness in the past 1 year

  • Clinically significant unstable psychiatric illness in past 6 months

  • History of unstable angina, myocardial infarction, advanced chronic heart failure, or clinically significant conduction abnormalities within 1 year prior to Screening

  • Indication of impaired renal or liver function

  • Have human immunodeficiency virus (HIV) infection

  • Have a significant systematic illness or infection in past 30 days

  • Relevant brain hemorrhage, bleeding disorder and cerebrovascular abnormalities

  • Any contraindications to brain magnetic resonance imaging (MRI) or PET scans

  • Alcohol or substance abuse in past 1 year

  • Taking blood thinners (except for aspirin at a prophylactic dose or less)

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Contacts and Locations

Locations

Site City State Country Postal Code
1 University of Alabama at Birmingham Birmingham Alabama United States 35233
2 Banner Alzheimer's Institute Phoenix Arizona United States 85006
3 Xenoscience Inc. Phoenix Arizona United States 85013
4 Banner Sun Health Research Institute Sun City Arizona United States 85351
5 Institute for Memory Impairments Irvine California United States 92607
6 Renewal Behavioral Health Long Beach California United States 85013
7 USC Keck School of Medicine Los Angeles California United States 90033
8 Hoag Memorial Hospital Presbyterian Newport Beach California United States 92663
9 Excell Research, Inc. Oceanside California United States 92056
10 Pacific Neuroscience Medical Group Oxnard California United States 93030
11 Anderson Clinical Research Redlands California United States 92354
12 Pacific Research Network San Diego California United States 92103
13 University of California San Diego Medical Center San Diego California United States 92103
14 California Pacific Medical Center San Francisco California United States 94114
15 Syrentis Clinical Research Santa Ana California United States 92705
16 St Joseph Heritage Healthcare Santa Rosa California United States 95403
17 Stanford University Medical Center Stanford California United States 94305
18 University Of Colorado Denver Aurora Colorado United States 80045
19 IMMUNOe International Research Centers Thornton Colorado United States 80233
20 Associated Neurologists of Southern Connecticut, PC Fairfield Connecticut United States 06824
21 Yale University School Of Medicine New Haven Connecticut United States 06520
22 Research Center for Clinical Studies, Inc. Norwalk Connecticut United States 06851
23 JEM Research Institute Atlantis Florida United States 33462
24 Bradenton Research Center, Inc. Bradenton Florida United States 34205
25 Meridien Research Brooksville Florida United States 34601
26 Quantum Laboratories Inc. Deerfield Beach Florida United States 33064
27 Infinity Clinical Research, LLC Hollywood Florida United States 33021
28 Mayo Clinic in Florida Jacksonville Florida United States 32224
29 Renstar Medical Research Ocala Florida United States 34470
30 Clinical Neuroscience Solutions, Inc. Orlando Florida United States 32801
31 Axiom Clinical Research of Florida Tampa Florida United States 33609
32 Emory University Cognitive Neurology Clinic & ADRC Atlanta Georgia United States 30329
33 Medical Research Health and Education Foundation, Inc Columbus Georgia United States 31909
34 NeuroStudies.net, LLC Decatur Georgia United States 30033
35 Josephson, Wallack, Munshower Neurology, PC Indianapolis Indiana United States 46256
36 McLean Hospital Belmont Massachusetts United States 02478
37 Boston Center for Memory Newton Massachusetts United States 05201
38 Hattiesburg Clinic, PA Hattiesburg Mississippi United States 39401
39 Cleveland Clinic Lou Ruvo Center for Brain Health Las Vegas Nevada United States 89106
40 ActivMed Practices & Research Portsmouth New Hampshire United States 03801
41 AdvanceMed Research Lawrenceville New Jersey United States 08648
42 Empire Neurology, PC Latham New York United States 12110
43 Weill Cornell Medical College-New York Presbyterian Hospital New York New York United States 10021
44 Mount Sinai School of Medicine New York New York United States 10029
45 PMG Research of Winston-Salem, LLC Winston-Salem North Carolina United States 27103
46 Wake Forest Baptist Health Winston-Salem North Carolina United States 27103
47 Ohio State University Medical Center Dublin Ohio United States 43017
48 Lehigh Center for Clinical Research, LLC Allentown Pennsylvania United States 18104
49 Penn Memory Center Philadelphia Pennsylvania United States 19104
50 Rhode Island Hospital Providence Rhode Island United States 02903
51 Roper St. Francis Healthcare North Charleston South Carolina United States 29406-6076
52 Senior Adult Specialty Research Austin Texas United States 78757
53 The Methodist Hospital Research Institute Houston Texas United States 77030
54 Clinical Trial Network Houston Texas United States 77074
55 University of Utah Health Sciences Center Salt Lake City Utah United States 84132
56 Clinical Neuroscience Research Association, Inc Bennington Vermont United States 05201
57 University of Washington Medical Center Seattle Washington United States 98195
58 Northwest Neurological, PLLC Spokane Washington United States 99202
59 A.Z. Klina Brasschaat Belgium
60 AZ Sint-Jan Brugge Brugge Belgium 8000
61 Universitair Ziekenhuis Brussel Bruxelles Belgium 1090
62 Centre Neurologique & de Réadaptation Fonctionnelle Fraiture Belgium 4557
63 Universitair Ziekenhuis Gent Gent Belgium 9000
64 AZ Groeninge - Campus Kennedylaan Kortrijk Belgium 8500
65 UZ Leuven Leuven Belgium 3000
66 AZ Delta Roeselare Belgium 8800
67 Health Research. Kamloops British Columbia Canada
68 Health Research West Vancouver British Columbia Canada
69 True North Clinical Research - Halifax Inc. Halifax Nova Scotia Canada B3S 1M7
70 True North Clinical Research Kentville, Inc Kentville Nova Scotia Canada B4N 4K9
71 JBN Medical Diagnostic Services Inc. Burlington Ontario Canada L7M 4Y1
72 St. Joseph's HC- Parkwood Institute London Ontario Canada N6C 5J1
73 Bruyere Continuing Care Ottawa Ontario Canada K1N 5C8
74 Kawartha Regional Memory Clinic Peterborough Ontario Canada K9H 2P4
75 Toronto Western Hospital Toronto Ontario Canada M5T 2S8
76 Recherches Neuro-Hippocampe Inc. Gatineau Quebec Canada J8T 8J1
77 Recherche Sepmus, Inc. Greenfield Park Quebec Canada J4V 2J2
78 DIEX Recherche Sherbrooke Inc. Sherbrooke Quebec Canada J1H 1Z1
79 Douglas Hospital Research Centre Verdun Quebec Canada H4H 1R3
80 Terveystalo Kamppi Helsinki Finland 00100
81 Itä-Suomen yliopisto, Aivotutkimusyksikkö Kuopio Finland 70210
82 CRST, Clinical Research Services Turku Turku Finland 20520
83 Hôpital de la Timone Marseille Bouches-du-Rhône France 13385
84 CHU de Toulouse - Hôpital Purpan Toulouse cedex 9 Haute Garonne France 31059
85 Centre de Recherche Clinique du Gérontopôle - Cité de la Santé Toulouse Haute Garonne France 31052
86 Hôpital Gui de Chauliac Montpellier Herault France 34295
87 CHU Rennes - Hopital Pontchaillou Rennes cedex 09 Ille Et Vilaine France 35033
88 CHU Nantes - Hopital Nord Laënnec Nantes cedex 1 Loire Atlantique France 44093
89 Hopital Roger Salengro - CHU Lille Lille Cedex Nord France 59037
90 Hôpital des Charpennes Villeurbanne Rhone France 69100
91 Hôpital Fernand Widal Paris France 75010
92 Bezirkskrankenhaus Guenzburg Gunzburg Baden Wuerttemberg Germany 89312
93 ISPG - Institut fuer Studien zur Psychischen Gesundheit Mannheim Baden Wuerttemberg Germany 68165
94 Nervenfachaerztlichen Gemeinschaftspraxis Ulm Ulm Baden Wuerttemberg Germany 89078
95 Universitaetsklinikum Ulm Ulm Baden Wuerttemberg Germany 89081
96 Klinik Hohe Warte Bayreuth Bayreuth Bayern Germany 95445
97 Institut fuer Schlaganfall- und Demenzforschung (ISD) Muenchen Bayern Germany 81377
98 Klinikum rechts der Isar der TU Muenchen Muenchen Bayern Germany 81675
99 Neuropraxis Muenchen Sued Unterhaching Bayern Germany 82008
100 Neuro Centrum Odenwald Erbach Hessen Germany 64711
101 Universitaetsklinikum Duesseldorf AoeR Duesseldorf Nordrhein Westfalen Germany 40629
102 Universitaetsklinikum Muenster Muenster Nordrhein Westfalen Germany 48149
103 Zentrum f. Neurologisch- Psychiatrische Studien und Begutachtung Siegen Nordrhein Westfalen Germany 57076
104 Schwerpunktpraxis fuer Neurologie, Psychiatrie und Klinische Studien Bielefeld North Rhine-Westphalia Germany 33647
105 Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz Mainz Rheinland Pfalz Germany 55131
106 Klinikum Chemnitz gGmbH Chemnitz Sachsen Germany 09131
107 Kopfzentrum Leipzig Leipzig Sachsen Germany 04275
108 Klinikum Altenburger Land GmbH Altenburg Thueringen Germany 04600
109 emovis GmbH Berlin Germany 10629
110 Neurologie im Tempelhofer Hafen Berlin Germany 12099
111 Ospedale degli Infermi Ponderano Biella Italy 13875
112 Azienda Ospedaliera Card. G. Panico Tricase Lecce Italy 73039
113 ASST di Monza Monza Milano Italy 20052
114 Fondazione IRCCS Istituto Neurologico Carlo Besta Milano Italy 20133
115 Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone Palermo Italy 90100
116 Azienda Ospedaliera di Perugia Ospedale S. Maria della Misericordia Perugia Italy 06156
117 Fondazione Santa Lucia IRCCS Roma Italy 00179
118 Umberto I Pol. di Roma-Università di Roma La Sapienza Roma Italy 00185
119 Research Site Obu-shi Aichi-Ken Japan 474-8511
120 Research Site Toon-shi Ehime-Ken Japan 791-0295
121 Research Site Fukuoka-shi Fukuoka-Ken Japan 814-0180
122 Research Site Kurume-shi Fukuoka-Ken Japan 830-0011
123 Research Site Otake-shi Hiroshima-Ken Japan 739-0696
124 Research Site Amagasaki-shi Hyogo-Ken Japan 660-8511
125 Research site Himeji-shi Hyogo-Ken Japan 670-0981
126 Research Site Himeji-shi Hyogo-Ken Japan 672-8043
127 Research Site Kobe-shi Hyogo-Ken Japan 650-0047
128 Research Site Kita-gun Kagawa-Ken Japan 761-0793
129 Research Site Kyoto-shi Kyoto-Fu Japan 607-8113
130 Research Site Kyoto-shi Kyoto-Fu Japan 616-8255
131 Research Site Tsu-shi Mie-Ken Japan 514-8507
132 Research Site Nishisonogi Nagasaki-Ken Japan 851-2103
133 Research Site Yufu-shi Oita-Ken Japan 879-5593
134 Research Site Kurashiki-shi Okayama-Ken Japan 710-0813
135 Research Site Okayama-shi Okayama-Ken Japan 703-8265
136 Research Site Tsukuba-gun Okayama-Ken Japan 701-0304
137 Research Site Kishiwada-shi Osaka-Fu Japan 596-8522
138 Research Site Osaka-shi Osaka-Fu Japan 530-0001
139 Research Site Osaka-shi Osaka-Fu Japan 545-8586
140 Research Site Osaka-shi Osaka-Fu Japan 553-0003
141 Research Site Sennan-shi Osaka-Fu Japan 590-0503
142 Research Site Suita-shi Osaka-Fu Japan 565-0871
143 Research Site Iwata-shi Shizuoka-Ken Japan 438-0043
144 Research Site Shizuoka-shi Shizuoka-Ken Japan 420-8688
145 Research Site Shizuoka-shi Shizuoka-Ken Japan 424-8636
146 Alzheimer Research Center Amsterdam Netherlands 1081 GM
147 Erasmus Medisch Centrum Rotterdam Netherlands 3015 CE
148 Podlaskie Centrum Psychogeriatrii Bialystok Poland 15-732
149 PALLMED Sp. z o.o. Bydgoszcz Poland 85-796
150 Uniwersyteckie Centrum Kliniczne Gdansk Poland
151 Novo-Med Zielinski i wspolnicy Sp. j. Katowice Poland 40-650
152 SPZOZ Centralny Szpital Kliniczny UM w Lodzi Lodz Poland 92-216
153 Centrum Diagnostyczno - Terapeutyczne "MEDICUS" Sp.z o.o. Lubin Poland 59-300
154 Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie Lublin Poland 20-950
155 Neurologiczny NZOZ Centrum Leczenia SM Plewiska Poland 62-064
156 NZOZ "NEURO-KARD", "Ilkowski i Partnerzy" Sp. Partn. Lek. Poznan Poland 61-853
157 Centrum Medyczne Medyk Rzeszow Poland 35-055
158 Neuro-Care Gabriela Klodowska Slaskie Poland 41-100
159 NZOZ "SENIOR" Poradnia Psychogeriatryczna Sopot Poland 81-855
160 Osrodek Badan Klinicznych EUROMEDIS Szczecin Poland 70-111
161 mMED Maciej Czarnecki Warszawa Poland 01-697
162 Hospital General Universitario de Elche Elche Alicante Spain 3203
163 ALTHAIA Hospital Sant Joan de Deu Manresa Barcelona Spain 08243
164 Hospital Universitario Reina Sofía Cordoba Córdoba Spain 14011
165 Clinica Universidad de Navarra Pamplona Navarra Spain 31008
166 Hospital del Mar Barcelona Spain 08003
167 Hospital Universitari Quiron Dexeus Barcelona Spain 08028
168 Hospital Universitari de Bellvitge Barcelona Spain 8907
169 Hospital Universitari Arnau de Vilanova Lleida Spain 25198
170 Hospital Universitario Virgen Macarena Sevilla Spain 41009
171 Skånes Universitetssjukhus, Malmö Malmö Sweden 20502
172 Sahlgrenska Universitetssjukhuset, Mölndal Sjukhus Mölndal Sweden 43141
173 Karolinska Universitetssjukhuset, Huddinge Stockholm Sweden 14186
174 Akademiska Sjukhuset Uppsala Sweden 75185
175 Universitären Psychiatrischen Kliniken Basel (UPK) Basel Switzerland 4025
176 Medizinisches Zentrum MZB Biel Biel/Bienne Switzerland 2502
177 Hôpitaux Universitaires de Genève - HUG Geneve 14 Switzerland 1211
178 Centre Hospitalier Universitaire Vaudois Lausanne Switzerland CH-1011
179 Ospedale Civico Lugano Switzerland 6903
180 Institut fuer Regenerative Medizin (IREM) der Universitaet Zuerich, Zentrum fuer Praevention und Demenztherapie Schlieren Switzerland 8952

Sponsors and Collaborators

  • Biogen

Investigators

  • Study Director: Medical Director, Biogen

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Biogen
ClinicalTrials.gov Identifier:
NCT02484547
Other Study ID Numbers:
  • 221AD302
  • 2015-000967-15
First Posted:
Jun 29, 2015
Last Update Posted:
Sep 2, 2021
Last Verified:
Aug 1, 2021
Keywords provided by Biogen
Aducanumab
BIIB037
Additional relevant MeSH terms:
Alzheimer Disease

Study Results

Participant Flow

Recruitment Details Participants were enrolled at 181 investigative sites in the United States, Belgium, Canada, Finland, France, Germany, Italy, Japan, Netherlands, Poland, Spain, Sweden, and Switzerland from 15 September 2015 to 13 July 2018.
Pre-assignment Detail A total of 1643 participants with Alzhiemer's disease were enrolled and randomized in the study. Of these, 1638 participants received the study drug in placebo-controlled (PC) period. After completing PC period, 771 participants entered and dosed in long-term extension (LTE) period and no participants completed the study due to early termination of the study.
Arm/Group Title Placebo (PC Period) BIIB037 Low Dose (PC Period) BIIB037 High Dose (PC Period) BIIB037 Late Start: Low Dose (LTE Period) BIIB037 Late Start: High Dose (LTE Period) BIIB037 Early Start: Low Dose (LTE Period) BIIB037 Early Start: High Dose (LTE Period)
Arm/Group Description Participants received a maximum of 20 infusions of BIIB037-matching placebo intravenously (IV) in PC period, administered approximately once every 4 weeks for up to approximately 1.5 years. Participants received a maximum of 20 infusions of BIIB037 low dose IV in PC period, administered approximately once every 4 weeks for up to approximately 1.5 years. Participants received a maximum of 20 infusions of BIIB037 high dose IV in PC period, administered approximately once every 4 weeks for up to approximately 1.5 years. Following PC period, participants randomized to placebo received BIIB037 low dose, IV infusion, approximately every 4 weeks for up to 2 years in LTE period. Following PC period, participants randomized to placebo received BIIB037 high dose, IV infusion, approximately every 4 weeks for up to 2 years in LTE period. Following PC period, participants randomized to low dose BIIB037 continued to receive the same dose, IV infusion, approximately every 4 weeks for up to 2 years in LTE period. Following PC period, participants randomized to high dose BIIB037 continued to receive the same dose, IV infusion, approximately every 4 weeks for up to 2 years in LTE period.
Period Title: Placebo-Controlled Period
STARTED 548 543 547 0 0 0 0
COMPLETED 288 291 295 0 0 0 0
NOT COMPLETED 260 252 252 0 0 0 0
Period Title: Placebo-Controlled Period
STARTED 0 0 0 131 132 251 257
COMPLETED 0 0 0 0 0 0 0
NOT COMPLETED 0 0 0 131 132 251 257

Baseline Characteristics

Arm/Group Title Placebo (PC Period) BIIB037 Low Dose (PC Period) BIIB037 High Dose (PC Period) Total
Arm/Group Description Participants received a maximum of 20 infusions of BIIB037-matching placebo intravenously (IV) in PC period, administered approximately once every 4 weeks for up to approximately 1.5 years. Participants received a maximum of 20 infusions of BIIB037 low dose IV in PC period, administered approximately once every 4 weeks for up to approximately 1.5 years. Participants received a maximum of 20 infusions of BIIB037 high dose IV in PC period, administered approximately once every 4 weeks for up to approximately 1.5 years. Total of all reporting groups
Overall Participants 548 543 547 1638
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
70.8
(7.40)
70.6
(7.45)
70.6
(7.47)
70.7
(7.43)
Sex: Female, Male (Count of Participants)
Female
290
52.9%
269
49.5%
284
51.9%
843
51.5%
Male
258
47.1%
274
50.5%
263
48.1%
795
48.5%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native
1
0.2%
0
0%
0
0%
1
0.1%
Asian
47
8.6%
39
7.2%
42
7.7%
128
7.8%
Black or African American
1
0.2%
6
1.1%
4
0.7%
11
0.7%
White
431
78.6%
432
79.6%
422
77.1%
1285
78.4%
Not Reported Due to Confidentiality Regulations
67
12.2%
65
12%
75
13.7%
207
12.6%
Other
1
0.2%
1
0.2%
3
0.5%
5
0.3%
Unknown
0
0%
0
0%
1
0.2%
1
0.1%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino
22
4%
22
4.1%
23
4.2%
67
4.1%
Not Hispanic or Latino
470
85.8%
470
86.6%
461
84.3%
1401
85.5%
Not Reported Due to Confidentiality Regulations
56
10.2%
51
9.4%
62
11.3%
169
10.3%
Unknown
0
0%
0
0%
1
0.2%
1
0.1%

Outcome Measures

1. Primary Outcome
Title Change From Baseline in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) Score at Week 78
Description CDR-SB integrates assessments from 3 domains of cognition (memory, orientation, judgment/problem-solving) and 3 domains of function (community affairs, home/hobbies, personal care). Following caregiver interview and systematic patient examination, the rater assigns a score describing the participant's current performance level in each of these domains of life functioning. Prespecified severity anchors range from none = 0, questionable = 0.5, mild = 1, moderate = 2 to severe = 3 (the personal care domain omits the 0.5 score). "Sum of boxes" scoring methodology sums the score for each of the 6 domains and provides a value ranging from 0 to 18 that can change in increments of 0.5 or greater. Higher scores indicate greater disease severity. Mixed model for repeated measures (MMRM) analysis was used to analyze change from baseline in CDR-SB. A positive change from baseline indicates clinical decline.
Time Frame Baseline, Week 78

Outcome Measure Data

Analysis Population Description
ITT was defined as all randomized participants who had received at least one dose of study treatment (Aducanumab or Placebo). 'Number of Participants Analyzed' signifies number of participants analyzed in this outcome measure.
Arm/Group Title Placebo (PC Period) BIIB037 Low Dose (PC Period) BIIB037 High Dose (PC Period)
Arm/Group Description Participants received a maximum of 20 infusions of BIIB037-matching placebo intravenously (IV) in PC period, administered approximately once every 4 weeks for up to approximately 1.5 years. Participants received a maximum of 20 infusions of BIIB037 low dose IV in PC period, administered approximately once every 4 weeks for up to approximately 1.5 years. Participants received a maximum of 20 infusions of BIIB037 high dose IV in PC period, administered approximately once every 4 weeks for up to approximately 1.5 years.
Measure Participants 288 290 299
Mean (Standard Error) [score on a scale]
1.74
(0.115)
1.47
(0.116)
1.35
(0.115)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (PC Period), BIIB037 Low Dose (PC Period)
Comments Adjusted mean for each treatment group (Placebo, BIIB037 Low Dose, BIIB037 High Dose), difference with Placebo, 95% confidence interval and p-value at each time point were based on an MMRM model, with change from baseline in CDR-SB as dependent variable and with fixed effects of treatment group, categorical visit, treatment-by-visit interaction, baseline CDR-SB, baseline CDR-SB by visit interaction, baseline MMSE, AD symptomatic medication use at baseline, region, and laboratory ApoE status.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.0901
Comments
Method MMRM
Comments
Method of Estimation Estimation Parameter Difference
Estimated Value -0.26
Confidence Interval (2-Sided) 95%
-0.569 to 0.041
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (PC Period), BIIB037 High Dose (PC Period)
Comments Adjusted mean for each treatment group (Placebo, BIIB037 Low Dose, BIIB037 High Dose), difference with Placebo, 95% confidence interval and p-value at each time point were based on an MMRM model, with change from baseline in CDR-SB as dependent variable and with fixed effects of treatment group, categorical visit, treatment-by-visit interaction, baseline CDR-SB, baseline CDR-SB by visit.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.0120
Comments
Method MMRM
Comments
Method of Estimation Estimation Parameter Difference
Estimated Value -0.39
Confidence Interval (2-Sided) 95%
-0.694 to -0.086
Parameter Dispersion Type:
Value:
Estimation Comments
2. Secondary Outcome
Title Change From Baseline in Mini Mental State Examination (MMSE) Score at Week 78
Description The MMSE is a widely used performance-based test of global cognitive status. It consists of 11 tasks that assess orientation, word recall, attention and calculation, language abilities, and visuospatial functions. The scores from the 11 tests are combined to obtain the total score, which ranges from 0 to 30, with lower scores over time indicating increasing cognitive impairment. MMRM analysis was used to analyze change from baseline in MMSE. A negative change from baseline indicates clinical decline.
Time Frame Baseline, Week 78

Outcome Measure Data

Analysis Population Description
ITT was defined as all randomized participants who had received at least one dose of study treatment (Aducanumab or Placebo). 'Number of Participants Analyzed' signifies number of participants analyzed in this outcome measure.
Arm/Group Title Placebo (PC Period) BIIB037 Low Dose (PC Period) BIIB037 High Dose (PC Period)
Arm/Group Description Participants received a maximum of 20 infusions of BIIB037-matching placebo intravenously (IV) in PC period, administered approximately once every 4 weeks for up to approximately 1.5 years. Participants received a maximum of 20 infusions of BIIB037 low dose IV in PC period, administered approximately once every 4 weeks for up to approximately 1.5 years. Participants received a maximum of 20 infusions of BIIB037 high dose IV in PC period, administered approximately once every 4 weeks for up to approximately 1.5 years.
Measure Participants 288 293 299
Mean (Standard Error) [score on a scale]
-3.3
(0.22)
-3.3
(0.22)
-2.7
(0.21)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (PC Period), BIIB037 Low Dose (PC Period)
Comments Adjusted mean for each treatment group (Placebo, BIIB037 Low Dose, BIIB037 High Dose), difference from Placebo, 95% confidence interval and p-value at each time point were based on an MMRM model, with change from baseline in MMSE as dependent variable and with fixed effects of treatment group, categorical visit, treatment-by-visit interaction, baseline MMSE, baseline MMSE by visit interaction, AD symptomatic medication use at baseline, region, and laboratory ApoE status.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.7578
Comments
Method MMRM
Comments
Method of Estimation Estimation Parameter Difference
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.65 to 0.48
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (PC Period), BIIB037 High Dose (PC Period)
Comments Adjusted mean for each treatment group (Placebo, BIIB037 Low Dose, BIIB037 High Dose), difference from Placebo, 95% confidence interval and p-value at each time point were based on an MMRM model, with change from baseline in MMSE as dependent variable and with fixed effects of treatment group, categorical visit, treatment-by-visit interaction, baseline MMSE, baseline MMSE by visit interaction, AD symptomatic medication use at baseline, region, and laboratory ApoE status.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.0493
Comments
Method MMRM
Comments
Method of Estimation Estimation Parameter Difference
Estimated Value 0.6
Confidence Interval (2-Sided) 95%
0.00 to 1.13
Parameter Dispersion Type:
Value:
Estimation Comments
3. Secondary Outcome
Title Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (13 Items) (ADAS-Cog 13) at Week 78
Description ADAS-Cog13 comprises both cognitive tasks and clinical ratings of cognitive performance. The scale items capture word recall, ability to follow commands, the ability to correctly copy or draw an image, naming, the ability to interact with everyday objects, orientation, word recognition, memory, comprehension of spoken language, word-finding, and language ability, with a measure for delayed word recall and concentration/distractibility. The total score ranges from 0 to 85. An increase in score over time indicates increasing cognitive impairment. MMRM analysis was used to analyze change from baseline in ADAS-Cog 13. A positive change from baseline indicates clinical decline.
Time Frame Baseline, Week 78

Outcome Measure Data

Analysis Population Description
ITT was defined as all randomized participants who had received at least one dose of study treatment (Aducanumab or Placebo). 'Number of Participants Analyzed' signifies number of participants analyzed in this outcome measure.
Arm/Group Title Placebo (PC Period) BIIB037 Low Dose (PC Period) BIIB037 High Dose (PC Period)
Arm/Group Description Participants received a maximum of 20 infusions of BIIB037-matching placebo intravenously (IV) in PC period, administered approximately once every 4 weeks for up to approximately 1.5 years. Participants received a maximum of 20 infusions of BIIB037 low dose IV in PC period, administered approximately once every 4 weeks for up to approximately 1.5 years. Participants received a maximum of 20 infusions of BIIB037 high dose IV in PC period, administered approximately once every 4 weeks for up to approximately 1.5 years.
Measure Participants 287 289 293
Mean (Standard Error) [score on a scale]
5.162
(0.4049)
4.461
(0.4074)
3.763
(0.4036)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (PC Period), BIIB037 Low Dose (PC Period)
Comments Adjusted mean for each treatment group(Placebo,BIIB037 Low Dose,BIIB037 High Dose),difference from Placebo, 95% confidence interval and p-value at each time point were based on an MMRM model, with change from baseline in ADASCog 13 as dependent variable and with fixed effects of treatment group,categorical visit,treatment-by-visit interaction,baseline ADAS-Cog 13,baseline ADAS-Cog 13 by visit interaction,baseline MMSE,AD symptomatic medication use at baseline,region, and laboratory ApoE status.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.1962
Comments
Method MMRM
Comments
Method of Estimation Estimation Parameter Difference
Estimated Value -0.701
Confidence Interval (2-Sided) 95%
-1.7649 to 0.3627
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (PC Period), BIIB037 High Dose (PC Period)
Comments Adjusted mean for each treatment group(Placebo,BIIB037 Low Dose,BIIB037 High Dose),difference from Placebo, 95% confidence interval and p-value at each time point were based on an MMRM model, with change from baseline in ADASCog 13 as dependent variable and with fixed effects of treatment group,categorical visit,treatment-by-visit interaction,baseline ADAS-Cog 13,baseline ADAS-Cog 13 by visit interaction,baseline MMSE,AD symptomatic medication use at baseline,region, and laboratory ApoE status.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.0097
Comments
Method MMRM
Comments
Method of Estimation Estimation Parameter Difference
Estimated Value -1.400
Confidence Interval (2-Sided) 95%
-2.4596 to -0.3396
Parameter Dispersion Type:
Value:
Estimation Comments
4. Secondary Outcome
Title Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (Mild Cognitive Impairment Version) (ADCS-ADL-MCI) Score at Week 78
Description The ADCS-ADL-MCI consists of 17 instrumental items (e.g., shopping, preparing meals, using household appliances) and 1 basic item (getting dressed). Ratings reflect caregiver observations about the patient's actual functioning over the previous month and provide an assessment of change in the functional state of the participant over time. The total score ranges from 0 to 53, with lower values over time reflecting functional deterioration. MMRM analysis was used to analyze change from baseline in ADAS-ADL-MCI. A negative change from baseline indicates clinical decline.
Time Frame Baseline, Week 78

Outcome Measure Data

Analysis Population Description
ITT was defined as all randomized participants who had received at least one dose of study treatment (Aducanumab or Placebo). 'Number of Participants Analyzed' signifies number of participants analyzed in this outcome measure.
Arm/Group Title Placebo (PC Period) BIIB037 Low Dose (PC Period) BIIB037 High Dose (PC Period)
Arm/Group Description Participants received a maximum of 20 infusions of BIIB037-matching placebo intravenously (IV) in PC period, administered approximately once every 4 weeks for up to approximately 1.5 years. Participants received a maximum of 20 infusions of BIIB037 low dose IV in PC period, administered approximately once every 4 weeks for up to approximately 1.5 years. Participants received a maximum of 20 infusions of BIIB037 high dose IV in PC period, administered approximately once every 4 weeks for up to approximately 1.5 years.
Measure Participants 283 286 295
Mean (Standard Error) [score on a scale]
-4.3
(0.38)
-3.5
(0.38)
-2.5
(0.38)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (PC Period), BIIB037 Low Dose (PC Period)
Comments Adjusted mean for each treatment group (Placebo, BIIB037 Low dose and BIIB037 High Dose), difference from Placebo,95% CI and p-value at each time point were based on an MMRM model, with change from baseline in ADCSADL-MCI as dependent variable and with fixed effects of treatment group, categorical visit, treatment-by-visit interaction, baseline ADCS-ADL-MCI, baseline ADCS-ADL-MCI by visit interaction, baseline MMSE, AD symptomatic medication use at baseline, region, and laboratory ApoE status.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.1515
Comments
Method MMRM
Comments
Method of Estimation Estimation Parameter Difference
Estimated Value 0.7
Confidence Interval (2-Sided) 95%
-0.27 to 1.73
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (PC Period), BIIB037 High Dose (PC Period)
Comments Adjusted mean for each treatment group (Placebo, BIIB037 Low dose and BIIB037 High Dose), difference from Placebo,95% CI and p-value at each time point were based on an MMRM model, with change from baseline in ADCSADL-MCI as dependent variable and with fixed effects of treatment group, categorical visit, treatment-by-visit interaction, baseline ADCS-ADL-MCI, baseline ADCS-ADL-MCI by visit interaction, baseline MMSE, AD symptomatic medication use at baseline, region, and laboratory ApoE status.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.0006
Comments
Method MMRM
Comments
Method of Estimation Estimation Parameter Difference
Estimated Value 1.7
Confidence Interval (2-Sided) 95%
0.75 to 2.74
Parameter Dispersion Type:
Value:
Estimation Comments

Adverse Events

Time Frame From First Dose to End of Study (up to 4 years)
Adverse Event Reporting Description The safety population was defined as all randomised participants who had received at least one dose of study treatment. In PC period, 1 participant randomized to placebo, inadvertently received 1 or more doses of active treatment (Low Dose) during the PC period. For participants affected, a participant was counted only once within each system organ class/preferred term/study period.
Arm/Group Title Placebo (PC Period) BIIB037 Low Dose (PC Period) BIIB037 High Dose (PC Period) BIIB037 Late Start: Low Dose (LTE Period) BIIB037 Late Start: High Dose (LTE Period) BIIB037 Early Start: Low Dose (LTE Period) BIIB037 Early Start: High Dose (LTE Period)
Arm/Group Description Participants received a maximum of 20 infusions of BIIB037-matching placebo intravenously (IV) in PC period, administered approximately once every 4 weeks for up to approximately 1.5 years. Participants received a maximum of 20 infusions of BIIB037 low dose IV in PC period, administered approximately once every 4 weeks for up to approximately 1.5 years. Participants received a maximum of 20 infusions of BIIB037 high dose IV in PC period, administered approximately once every 4 weeks for up to approximately 1.5 years. Following PC period, participants randomized to placebo received BIIB037 low dose, IV infusion, approximately every 4 weeks for up to 2 years in LTE period. Following PC period, participants randomized to placebo received BIIB037 high dose, IV infusion, approximately every 4 weeks for up to 2 years in LTE period. Following PC period, participants randomized to low dose BIIB037 continued to receive the same dose, IV infusion, approximately every 4 weeks for up to 2 years in LTE period. Following PC period, participants randomized to high dose BIIB037 continued to receive the same dose, IV infusion, approximately every 4 weeks for up to 2 years in LTE period.
All Cause Mortality
Placebo (PC Period) BIIB037 Low Dose (PC Period) BIIB037 High Dose (PC Period) BIIB037 Late Start: Low Dose (LTE Period) BIIB037 Late Start: High Dose (LTE Period) BIIB037 Early Start: Low Dose (LTE Period) BIIB037 Early Start: High Dose (LTE Period)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 5/547 (0.9%) 0/544 (0%) 6/547 (1.1%) 0/131 (0%) 0/132 (0%) 3/251 (1.2%) 0/257 (0%)
Serious Adverse Events
Placebo (PC Period) BIIB037 Low Dose (PC Period) BIIB037 High Dose (PC Period) BIIB037 Late Start: Low Dose (LTE Period) BIIB037 Late Start: High Dose (LTE Period) BIIB037 Early Start: Low Dose (LTE Period) BIIB037 Early Start: High Dose (LTE Period)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 81/547 (14.8%) 72/544 (13.2%) 73/547 (13.3%) 15/131 (11.5%) 9/132 (6.8%) 25/251 (10%) 25/257 (9.7%)
Blood and lymphatic system disorders
Iron deficiency anaemia 0/547 (0%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 1/251 (0.4%) 0/257 (0%)
Cardiac disorders
Acute coronary syndrome 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Acute left ventricular failure 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Acute myocardial infarction 0/547 (0%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 1/251 (0.4%) 1/257 (0.4%)
Angina pectoris 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Angina unstable 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Aortic valve incompetence 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Atrial fibrillation 2/547 (0.4%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 1/251 (0.4%) 0/257 (0%)
Atrial flutter 0/547 (0%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 1/251 (0.4%) 0/257 (0%)
Atrioventricular block second degree 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Bradycardia 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Cardiac arrest 0/547 (0%) 0/544 (0%) 2/547 (0.4%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Cardiac failure congestive 2/547 (0.4%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 1/251 (0.4%) 0/257 (0%)
Coronary artery disease 1/547 (0.2%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 2/257 (0.8%)
Ischaemic cardiomyopathy 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Myocardial infarction 2/547 (0.4%) 1/544 (0.2%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Sinus bradycardia 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Sinus node dysfunction 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Sinus tachycardia 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Stress cardiomyopathy 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Supraventricular extrasystoles 0/547 (0%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 1/257 (0.4%)
Ear and labyrinth disorders
Deafness bilateral 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Meniere's disease 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Vertigo 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Endocrine disorders
Inappropriate antidiuretic hormone secretion 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Eye disorders
Age-related macular degeneration 0/547 (0%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 1/251 (0.4%) 0/257 (0%)
Cataract nuclear 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Retinal detachment 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 1/257 (0.4%)
Vitreous floaters 0/547 (0%) 0/544 (0%) 0/547 (0%) 1/131 (0.8%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Gastrointestinal disorders
Abdominal pain 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 1/131 (0.8%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Acquired oesophageal web 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Barrett's oesophagus 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Colitis 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Colitis ischaemic 0/547 (0%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 1/251 (0.4%) 0/257 (0%)
Constipation 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Diarrhoea 2/547 (0.4%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Diverticular perforation 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Diverticulum intestinal haemorrhagic 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Duodenal ulcer perforation 0/547 (0%) 1/544 (0.2%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Dysphagia 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Femoral hernia strangulated 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Gastritis 1/547 (0.2%) 0/544 (0%) 2/547 (0.4%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Gastrointestinal haemorrhage 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Gastrointestinal necrosis 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Gastrooesophageal reflux disease 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Haemorrhoidal haemorrhage 0/547 (0%) 2/544 (0.4%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 1/251 (0.4%) 0/257 (0%)
Haemorrhoids 0/547 (0%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 1/257 (0.4%)
Ileus 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Inguinal hernia 0/547 (0%) 2/544 (0.4%) 3/547 (0.5%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Intestinal obstruction 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Intestinal perforation 0/547 (0%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 1/257 (0.4%)
Large intestine polyp 2/547 (0.4%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 1/251 (0.4%) 0/257 (0%)
Nausea 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 1/131 (0.8%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Obstructive pancreatitis 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Pancreatitis 1/547 (0.2%) 1/544 (0.2%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Pancreatitis acute 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Pneumoperitoneum 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Rectal prolapse 0/547 (0%) 1/544 (0.2%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Vomiting 2/547 (0.4%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
General disorders
Asthenia 0/547 (0%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 1/251 (0.4%) 0/257 (0%)
Chest pain 0/547 (0%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 1/251 (0.4%) 1/257 (0.4%)
Death 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Discomfort 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Gait disturbance 1/547 (0.2%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 2/257 (0.8%)
Medical device site joint pain 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Non-cardiac chest pain 2/547 (0.4%) 1/544 (0.2%) 2/547 (0.4%) 0/131 (0%) 0/132 (0%) 1/251 (0.4%) 0/257 (0%)
Pyrexia 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Hepatobiliary disorders
Cholecystitis 0/547 (0%) 0/544 (0%) 0/547 (0%) 1/131 (0.8%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Cholecystitis acute 2/547 (0.4%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Cholelithiasis 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Hepatitis acute 0/547 (0%) 0/544 (0%) 0/547 (0%) 1/131 (0.8%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Jaundice 0/547 (0%) 0/544 (0%) 0/547 (0%) 1/131 (0.8%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Immune system disorders
Hypersensitivity 0/547 (0%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 1/251 (0.4%) 0/257 (0%)
Infections and infestations
Appendicitis 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Bacterial infection 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Bronchitis 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Cellulitis 0/547 (0%) 1/544 (0.2%) 2/547 (0.4%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Cystitis klebsiella 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Erysipelas 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Gastroenteritis 0/547 (0%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 1/251 (0.4%) 0/257 (0%)
Gastroenteritis viral 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 1/257 (0.4%)
Human anaplasmosis 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Lymphangitis 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Otitis media 0/547 (0%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 1/132 (0.8%) 0/251 (0%) 0/257 (0%)
Pneumonia 2/547 (0.4%) 2/544 (0.4%) 1/547 (0.2%) 1/131 (0.8%) 1/132 (0.8%) 0/251 (0%) 0/257 (0%)
Pneumonia bacterial 0/547 (0%) 0/544 (0%) 0/547 (0%) 1/131 (0.8%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Pneumonia influenzal 0/547 (0%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 1/257 (0.4%)
Pneumonia respiratory syncytial viral 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Pulmonary sepsis 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 1/251 (0.4%) 0/257 (0%)
Sepsis 0/547 (0%) 0/544 (0%) 2/547 (0.4%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 1/257 (0.4%)
Urinary tract infection 1/547 (0.2%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 1/251 (0.4%) 0/257 (0%)
Urosepsis 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Injury, poisoning and procedural complications
Accident 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 1/257 (0.4%)
Accidental overdose 0/547 (0%) 1/544 (0.2%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Alcohol poisoning 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Animal attack 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Animal scratch 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Ankle fracture 2/547 (0.4%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Bone contusion 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Cardiac contusion 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Concussion 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Craniocerebral injury 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Epiphyseal fracture 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Fall 12/547 (2.2%) 9/544 (1.7%) 4/547 (0.7%) 2/131 (1.5%) 1/132 (0.8%) 1/251 (0.4%) 6/257 (2.3%)
Femoral neck fracture 3/547 (0.5%) 2/544 (0.4%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Foot fracture 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Gastrointestinal procedural complication 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Hand fracture 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Head injury 1/547 (0.2%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Hip fracture 0/547 (0%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 2/257 (0.8%)
Humerus fracture 0/547 (0%) 1/544 (0.2%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Joint dislocation 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 1/131 (0.8%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Lower limb fracture 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Lumbar vertebral fracture 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 1/131 (0.8%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Pelvic fracture 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Pubis fracture 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 1/132 (0.8%) 0/251 (0%) 0/257 (0%)
Pulmonary contusion 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Radius fracture 0/547 (0%) 1/544 (0.2%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Rib fracture 5/547 (0.9%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 1/257 (0.4%)
Road traffic accident 1/547 (0.2%) 2/544 (0.4%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Skin laceration 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Skull fracture 0/547 (0%) 0/544 (0%) 0/547 (0%) 1/131 (0.8%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Spinal fracture 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Subdural haematoma 0/547 (0%) 3/544 (0.6%) 2/547 (0.4%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 1/257 (0.4%)
Thoracic vertebral fracture 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Upper limb fracture 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Wrist fracture 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 1/257 (0.4%)
Investigations
Weight decreased 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Metabolism and nutrition disorders
Dehydration 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Hyperglycaemia 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Hypoglycaemia 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Hyponatraemia 0/547 (0%) 1/544 (0.2%) 1/547 (0.2%) 0/131 (0%) 1/132 (0.8%) 0/251 (0%) 0/257 (0%)
Musculoskeletal and connective tissue disorders
Arthritis 0/547 (0%) 0/544 (0%) 0/547 (0%) 1/131 (0.8%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Back pain 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 1/257 (0.4%)
Bursitis 0/547 (0%) 1/544 (0.2%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Intervertebral disc protrusion 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Muscular weakness 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Musculoskeletal pain 0/547 (0%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 1/257 (0.4%)
Musculoskeletal stiffness 0/547 (0%) 0/544 (0%) 0/547 (0%) 1/131 (0.8%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Osteoarthritis 2/547 (0.4%) 3/544 (0.6%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 1/251 (0.4%) 0/257 (0%)
Osteonecrosis 0/547 (0%) 1/544 (0.2%) 1/547 (0.2%) 1/131 (0.8%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Rhabdomyolysis 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Spinal osteoarthritis 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Vertebral foraminal stenosis 0/547 (0%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 1/251 (0.4%) 0/257 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 1/131 (0.8%) 1/132 (0.8%) 1/251 (0.4%) 0/257 (0%)
Adenocarcinoma pancreas 0/547 (0%) 0/544 (0%) 0/547 (0%) 1/131 (0.8%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Basal cell carcinoma 0/547 (0%) 2/544 (0.4%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 1/251 (0.4%) 0/257 (0%)
Bladder papilloma 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Breast cancer 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Cholangiocarcinoma 0/547 (0%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 1/251 (0.4%) 0/257 (0%)
Cholesteatoma 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Diffuse large b-cell lymphoma 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Endometrial adenocarcinoma 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Endometrial cancer 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Gastric cancer 1/547 (0.2%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Gastrointestinal neoplasm 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Invasive ductal breast carcinoma 1/547 (0.2%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 1/251 (0.4%) 0/257 (0%)
Invasive lobular breast carcinoma 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Lung adenocarcinoma stage iv 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 1/132 (0.8%) 0/251 (0%) 0/257 (0%)
Lung neoplasm malignant 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Malignant melanoma 0/547 (0%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 1/251 (0.4%) 0/257 (0%)
Malignant melanoma in situ 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Medullary thyroid cancer 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Metastatic neoplasm 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Oesophageal carcinoma 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Ovarian cancer 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Pancreatic carcinoma metastatic 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Pleural mesothelioma 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Prostate cancer 1/547 (0.2%) 2/544 (0.4%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Prostatic adenoma 0/547 (0%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 1/251 (0.4%) 0/257 (0%)
Salivary gland cancer 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Small cell lung cancer 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Squamous cell carcinoma 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Squamous cell carcinoma of the oral cavity 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
T-cell lymphoma 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Thymoma malignant 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Nervous system disorders
Amyloid related imaging abnormality-microhaemorrhages and haemosiderin deposits 0/547 (0%) 4/544 (0.7%) 2/547 (0.4%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Amyloid related imaging abnormality-oedema/effusion 1/547 (0.2%) 5/544 (0.9%) 8/547 (1.5%) 0/131 (0%) 1/132 (0.8%) 0/251 (0%) 0/257 (0%)
Carpal tunnel syndrome 0/547 (0%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 1/132 (0.8%) 0/251 (0%) 0/257 (0%)
Cerebellar infarction 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Cerebral haematoma 0/547 (0%) 0/544 (0%) 0/547 (0%) 1/131 (0.8%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Cerebral haemorrhage 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 1/132 (0.8%) 0/251 (0%) 0/257 (0%)
Cerebral infarction 2/547 (0.4%) 2/544 (0.4%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Cerebrovascular accident 1/547 (0.2%) 1/544 (0.2%) 0/547 (0%) 1/131 (0.8%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Dementia alzheimer's type 2/547 (0.4%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 1/251 (0.4%) 0/257 (0%)
Dizziness 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Embolic cerebral infarction 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Embolic stroke 0/547 (0%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 1/257 (0.4%)
Encephalopathy 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Focal dyscognitive seizures 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Generalised tonic-clonic seizure 1/547 (0.2%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Guillain-barre syndrome 0/547 (0%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 1/257 (0.4%)
Headache 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 1/131 (0.8%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Intracranial venous sinus thrombosis 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Ischaemic stroke 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 1/131 (0.8%) 0/132 (0%) 1/251 (0.4%) 1/257 (0.4%)
Lacunar infarction 0/547 (0%) 1/544 (0.2%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Loss of consciousness 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Memory impairment 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Metabolic encephalopathy 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Presyncope 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Quadriparesis 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Seizure 1/547 (0.2%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Sensorimotor disorder 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Superficial siderosis of central nervous system 0/547 (0%) 1/544 (0.2%) 3/547 (0.5%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Syncope 3/547 (0.5%) 2/544 (0.4%) 4/547 (0.7%) 0/131 (0%) 1/132 (0.8%) 2/251 (0.8%) 2/257 (0.8%)
Thrombotic stroke 0/547 (0%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 1/251 (0.4%) 0/257 (0%)
Toxic encephalopathy 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Transient ischaemic attack 1/547 (0.2%) 0/544 (0%) 2/547 (0.4%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 1/257 (0.4%)
Psychiatric disorders
Agitation 3/547 (0.5%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Anxiety 0/547 (0%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 1/257 (0.4%)
Behaviour disorder 0/547 (0%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 1/257 (0.4%)
Bipolar disorder 1/547 (0.2%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Confusional state 0/547 (0%) 1/544 (0.2%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Delirium 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Delusion 1/547 (0.2%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Depression 2/547 (0.4%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Intentional self-injury 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Mania 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Mental status changes 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Neuropsychiatric symptoms 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Psychotic disorder 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Somatic symptom disorder 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Suicidal ideation 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Suicide attempt 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Renal and urinary disorders
Acute kidney injury 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Calculus bladder 0/547 (0%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 1/251 (0.4%) 0/257 (0%)
Nephrolithiasis 0/547 (0%) 1/544 (0.2%) 1/547 (0.2%) 1/131 (0.8%) 0/132 (0%) 1/251 (0.4%) 0/257 (0%)
Prerenal failure 0/547 (0%) 0/544 (0%) 0/547 (0%) 1/131 (0.8%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Renal failure 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Urethral disorder 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Urethral stenosis 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Urinary retention 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Reproductive system and breast disorders
Adnexa uteri cyst 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Benign prostatic hyperplasia 1/547 (0.2%) 1/544 (0.2%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Cervical polyp 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Gynaecomastia 0/547 (0%) 0/544 (0%) 0/547 (0%) 1/131 (0.8%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Ovarian cyst 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Spermatic cord cyst 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 1/257 (0.4%)
Haemothorax 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 1/257 (0.4%)
Laryngeal oedema 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Lung perforation 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Pneumonia aspiration 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 1/251 (0.4%) 0/257 (0%)
Pneumothorax 0/547 (0%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 1/257 (0.4%)
Pulmonary embolism 1/547 (0.2%) 0/544 (0%) 2/547 (0.4%) 0/131 (0%) 0/132 (0%) 1/251 (0.4%) 0/257 (0%)
Respiratory failure 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Vascular disorders
Aortic aneurysm rupture 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Aortic stenosis 0/547 (0%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Deep vein thrombosis 1/547 (0.2%) 1/544 (0.2%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Hypertension 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Hypertensive crisis 2/547 (0.4%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Hypertensive urgency 1/547 (0.2%) 0/544 (0%) 1/547 (0.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Hypotension 1/547 (0.2%) 0/544 (0%) 0/547 (0%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Other (Not Including Serious) Adverse Events
Placebo (PC Period) BIIB037 Low Dose (PC Period) BIIB037 High Dose (PC Period) BIIB037 Late Start: Low Dose (LTE Period) BIIB037 Late Start: High Dose (LTE Period) BIIB037 Early Start: Low Dose (LTE Period) BIIB037 Early Start: High Dose (LTE Period)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 353/547 (64.5%) 385/544 (70.8%) 428/547 (78.2%) 55/131 (42%) 56/132 (42.4%) 87/251 (34.7%) 107/257 (41.6%)
Gastrointestinal disorders
Diarrhoea 29/547 (5.3%) 38/544 (7%) 42/547 (7.7%) 3/131 (2.3%) 7/132 (5.3%) 9/251 (3.6%) 6/257 (2.3%)
Nausea 27/547 (4.9%) 29/544 (5.3%) 31/547 (5.7%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
General disorders
Fatigue 37/547 (6.8%) 27/544 (5%) 34/547 (6.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Infections and infestations
Nasopharyngitis 91/547 (16.6%) 71/544 (13.1%) 89/547 (16.3%) 6/131 (4.6%) 7/132 (5.3%) 18/251 (7.2%) 19/257 (7.4%)
Upper respiratory tract infection 41/547 (7.5%) 42/544 (7.7%) 38/547 (6.9%) 8/131 (6.1%) 2/132 (1.5%) 13/251 (5.2%) 11/257 (4.3%)
Urinary tract infection 36/547 (6.6%) 39/544 (7.2%) 29/547 (5.3%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Injury, poisoning and procedural complications
Fall 62/547 (11.3%) 59/544 (10.8%) 73/547 (13.3%) 13/131 (9.9%) 7/132 (5.3%) 15/251 (6%) 32/257 (12.5%)
Musculoskeletal and connective tissue disorders
Arthralgia 31/547 (5.7%) 17/544 (3.1%) 34/547 (6.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Back pain 36/547 (6.6%) 38/544 (7%) 42/547 (7.7%) 8/131 (6.1%) 3/132 (2.3%) 9/251 (3.6%) 10/257 (3.9%)
Nervous system disorders
Amyloid related imaging abnormality-microhaemorrhages and haemosiderin deposits 37/547 (6.8%) 86/544 (15.8%) 106/547 (19.4%) 18/131 (13.7%) 11/132 (8.3%) 12/251 (4.8%) 21/257 (8.2%)
Amyloid related imaging abnormality-oedema/effusion 12/547 (2.2%) 138/544 (25.4%) 183/547 (33.5%) 23/131 (17.6%) 31/132 (23.5%) 11/251 (4.4%) 22/257 (8.6%)
Dizziness 43/547 (7.9%) 42/544 (7.7%) 55/547 (10.1%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Headache 84/547 (15.4%) 109/544 (20%) 107/547 (19.6%) 10/131 (7.6%) 13/132 (9.8%) 20/251 (8%) 19/257 (7.4%)
Superficial siderosis of central nervous system 14/547 (2.6%) 51/544 (9.4%) 71/547 (13%) 13/131 (9.9%) 17/132 (12.9%) 4/251 (1.6%) 10/257 (3.9%)
Psychiatric disorders
Anxiety 21/547 (3.8%) 30/544 (5.5%) 19/547 (3.5%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Confusional state 15/547 (2.7%) 16/544 (2.9%) 28/547 (5.1%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Depression 28/547 (5.1%) 29/544 (5.3%) 23/547 (4.2%) 0/131 (0%) 0/132 (0%) 0/251 (0%) 0/257 (0%)
Respiratory, thoracic and mediastinal disorders
Cough 28/547 (5.1%) 24/544 (4.4%) 33/547 (6%) 4/131 (3.1%) 4/132 (3%) 7/251 (2.8%) 14/257 (5.4%)

Limitations/Caveats

The study was halted prematurely based on a prespecified futility analysis and not based on safety concerns. Participants discontinued due to study termination are included in "Reason not Specified" category in participant flow tables above.

More Information

Certain Agreements

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

Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information.PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.

Results Point of Contact

Name/Title Biogen Study Medical Director
Organization Biogen
Phone 866-633-4636
Email clinicaltrials@biogen.com
Responsible Party:
Biogen
ClinicalTrials.gov Identifier:
NCT02484547
Other Study ID Numbers:
  • 221AD302
  • 2015-000967-15
First Posted:
Jun 29, 2015
Last Update Posted:
Sep 2, 2021
Last Verified:
Aug 1, 2021