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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03444870




Registration number
NCT03444870
Ethics application status
Date submitted
19/02/2018
Date registered
23/02/2018

Titles & IDs
Public title
Efficacy and Safety Study of Gantenerumab in Participants With Early Alzheimer's Disease (AD)
Scientific title
A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study of Gantenerumab in Patients With Early (Prodromal to Mild) Alzheimer's Disease
Secondary ID [1] 0 0
2017-001364-38
Secondary ID [2] 0 0
WN29922
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer Disease 0 0
Condition category
Condition code
Neurological 0 0 0 0
Alzheimer's disease
Neurological 0 0 0 0
Dementias

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Gantenerumab
Treatment: Drugs - Placebo

Experimental: Gantenerumab - Gantenerumab will be administered as SC injections with gradual uptitration.

Placebo comparator: Placebo - Placebo will be administered as SC injections with gradual uptitration.


Treatment: Drugs: Gantenerumab
Gantenerumab will be administered as per the schedule specified in the respective arm.

Treatment: Drugs: Placebo
Placebo will be administered as per the schedule specified in the respective arm.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
DBT Period: Change From Baseline to Week 116 in Global Outcome, as Measured by CDR-SB
Timepoint [1] 0 0
Baseline, Week 116
Primary outcome [2] 0 0
China Extension: DBT Period: Change From Baseline to Week 116 in Global Outcome, as Measured by CDR-SB
Timepoint [2] 0 0
Baseline, Week 116
Secondary outcome [1] 0 0
DBT Period: Change From Baseline to Week 116 in Alzheimer Disease Assessment Scale-Cognition Subscale 13 (ADAS-Cog13) Score
Timepoint [1] 0 0
Baseline, Week 116
Secondary outcome [2] 0 0
DBT Period: Change From Baseline to Week 116 in Alzheimer's Disease Cooperative Study- Activities of Daily Living (ADCS-ADL) Total Score
Timepoint [2] 0 0
Baseline, Week 116
Secondary outcome [3] 0 0
DBT Period: Change From Baseline to Week 116 in Functional Activities Questionnaire (FAQ) Score
Timepoint [3] 0 0
Baseline, Week 116
Secondary outcome [4] 0 0
DBT Period: Change From Baseline to Week 116 in Mini-Mental State Examination (MMSE) Total Score
Timepoint [4] 0 0
Baseline, Week 116
Secondary outcome [5] 0 0
DBT Period: Change From Baseline to Week 116 in Alzheimer Disease Assessment Scale-Cognition Subscale 11 (ADAS-Cog11) Score
Timepoint [5] 0 0
Baseline, Week 116
Secondary outcome [6] 0 0
DBT Period: Change From Baseline to Week 116 in Verbal Fluency Task (VFT) Score
Timepoint [6] 0 0
Baseline, Week 116
Secondary outcome [7] 0 0
DBT Period: Change From Baseline to Week 116 in the Coding (Digit Symbol Substitution Test [DSST]) Subtest
Timepoint [7] 0 0
Baseline, Week 116
Secondary outcome [8] 0 0
DBT Period: Change From Baseline to Week 116 in Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living (ADCS-iADL) Instrumental Score
Timepoint [8] 0 0
Baseline, Week 116
Secondary outcome [9] 0 0
DBT Period: Number of Participants With at Least One Adverse Event (AE)
Timepoint [9] 0 0
From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 131 weeks)
Secondary outcome [10] 0 0
DBT Period: Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS)
Timepoint [10] 0 0
From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 131 weeks)
Secondary outcome [11] 0 0
DBT Period: Number of Participants With at Least One Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Magnetic Resonance Imaging (MRI) Finding
Timepoint [11] 0 0
From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 131 weeks)
Secondary outcome [12] 0 0
DBT Period: Number of Participants With at Least One Amyloid-Related Imaging Abnormalities-Haemosiderin Deposition (ARIA-H) MRI Finding
Timepoint [12] 0 0
From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 131 weeks)
Secondary outcome [13] 0 0
DBT Period: Number of Participants With Injection-Site Reactions
Timepoint [13] 0 0
From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 131 weeks)
Secondary outcome [14] 0 0
DBT Period: Number of Participants With Anti-Drug Antibodies (ADA) to Gantenerumab
Timepoint [14] 0 0
From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 131 weeks)
Secondary outcome [15] 0 0
DBT Period: Change From Baseline to Week 116 in Brain Amyloid Load as Measured by Amyloid Positron Emission Tomography (PET) Scan in a Subset of Participants
Timepoint [15] 0 0
Baseline, Week 116
Secondary outcome [16] 0 0
DBT Period: Change From Baseline to Week 116 in Brain Tau Load, as Measured by Tau PET Scan in a Subset of Participants
Timepoint [16] 0 0
Baseline, Week 116
Secondary outcome [17] 0 0
DBT Period: Percent Change From Baseline to Week 116 in Cerebrospinal Fluid (CSF) Marker of Disease in a Subset of Participants - Total Tau (tTau)
Timepoint [17] 0 0
Baseline, Week 116
Secondary outcome [18] 0 0
DBT Period: Percent Change From Baseline to Week 116 in CSF Marker of Disease in a Subset of Participants - Phosphorylated Tau (pTau-181)
Timepoint [18] 0 0
Baseline, Week 116
Secondary outcome [19] 0 0
DBT Period: Percent Change From Baseline to Week 116 in CSF Marker of Disease in a Subset of Participants - Neurofilament Light Chain (NFL)
Timepoint [19] 0 0
Baseline, Week 116
Secondary outcome [20] 0 0
DBT Period: Percent Change From Baseline to Week 116 in CSF Marker of Disease in a Subset of Participants - Neurogranin
Timepoint [20] 0 0
Baseline, Week 116
Secondary outcome [21] 0 0
China - DBT Period: Change From Baseline to Week 116 in ADAS-Cog13 Score
Timepoint [21] 0 0
Baseline, Week 116
Secondary outcome [22] 0 0
China - DBT Period: Change From Baseline to Week 116 in ADCS-ADL Total Score
Timepoint [22] 0 0
Baseline, Week 116
Secondary outcome [23] 0 0
China - DBT Period: Change From Baseline to Week 116 in FAQ Score
Timepoint [23] 0 0
Baseline, Week 116
Secondary outcome [24] 0 0
China - DBT Period: DBT Period: Change From Baseline to Week 116 in MMSE Total Score
Timepoint [24] 0 0
Baseline, Week 116
Secondary outcome [25] 0 0
China - DBT Period: Change From Baseline to Week 116 in ADAS-Cog11 Score
Timepoint [25] 0 0
Baseline, Week 116
Secondary outcome [26] 0 0
China - DBT Period: Change From Baseline to Week 116 in VFT Score
Timepoint [26] 0 0
Baseline, Week 116
Secondary outcome [27] 0 0
China - DBT Period: Change From Baseline to Week 116 in the Coding (DSST) Subtest
Timepoint [27] 0 0
Baseline, Week 116
Secondary outcome [28] 0 0
China - DBT Period: Number of Participants With at Least One AE
Timepoint [28] 0 0
From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 124 weeks)
Secondary outcome [29] 0 0
China - DBT Period: Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS
Timepoint [29] 0 0
From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 124 weeks)
Secondary outcome [30] 0 0
China - DBT Period: Number of Participants With at Least One ARIA-E MRI Finding
Timepoint [30] 0 0
From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 124 weeks)
Secondary outcome [31] 0 0
China - DBT Period: Number of Participants With at Least One ARIA-H MRI Finding
Timepoint [31] 0 0
From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 124 weeks)
Secondary outcome [32] 0 0
China - DBT Period: Number of Participants With Injection-Site Reactions
Timepoint [32] 0 0
From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 124 weeks)
Secondary outcome [33] 0 0
OLE Period: Number of Participants With at Least One AEs
Timepoint [33] 0 0
From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 68 weeks)
Secondary outcome [34] 0 0
OLE Period: Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS
Timepoint [34] 0 0
From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 68 weeks)
Secondary outcome [35] 0 0
OLE Period: Number of Participants With at Least One ARIA-H MRI Finding
Timepoint [35] 0 0
From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 68 weeks)
Secondary outcome [36] 0 0
OLE Period: Number of Participants With at Least One ARIA-E MRI Finding
Timepoint [36] 0 0
From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 68 weeks)

Eligibility
Key inclusion criteria
Key Inclusion criteria:

* Meets National Institute on Aging/Alzheimer's Association (NIAAA) core clinical criteria for probable AD dementia or prodromal AD (consistent with the NIAAA diagnostic criteria and guidelines for mild cognitive impairment)
* Evidence of the AD pathological process, as confirmed by CSF tau/A-beta42or amyloid PET scan
* Demonstrated abnormal memory function
* MMSE score greater than or equal to 22 (= 22)
* Clinical dementia rating-global score (CDR-GS) of 0.5 or 1.0
* Availability of a reliable study partner who accepts to participate in study procedures throughout the 2 years duration of study
* If receiving symptomatic AD medications, the dosing regimen must have been stable for 3 months prior to screening and until randomization
* For enrollment in the China extension, patients must have residence in mainland China, Hong Kong, or Taiwan and be of Chinese ancestry
* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods

Key
Minimum age
50 Years
Maximum age
90 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

* Any evidence of a condition other than AD that may affect cognition
* History of schizophrenia, schizoaffective disorder, major depression, or bipolar disorder
* History or presence of clinically evident systemic vascular disease that in the opinion of the investigator has the potential to affect cognitive function
* History or presence of clinically evident cerebrovascular disease
* History or presence of posterior reversible encephalopathy syndrome
* History or presence of any stroke with clinical symptoms within the past 12 months, or documented history within the last 6 months of an acute event that is consistent with a transient ischemic attack
* History of severe, clinically significant CNS trauma
* History or presence of intracranial mass (e.g., glioma, meningioma) that could potentially impair cognition
* Presence of infections that affect brain function or history of infections that resulted in neurologic sequelae
* History or presence of systemic autoimmune disorders that potentially cause progressive neurologic disease with associated cognitive deficits
* At risk for suicide in the opinion of the investigator
* Alcohol and/or substance abuse or dependants in past 2 years
* Relevant brain hemorrhage, bleeding disorder and cerebrovascular abnormalities
* Any contraindications to brain MRI
* Unstable or clinically significant cardiovascular, kidney or liver disease
* Uncontrolled hypertension
* Unstable or clinically significant cardiovascular disease
* Abnormal thyroid function
* Patients with evidence of folic acid deficiency

Exclusion for Open-Label Extension (OLE):

* Discontinued from study treatment during the double-blind treatment period
* Received any other investigational medication during the double-blind treatment period or after the end of double-blind treatment
* Participation in the OLE deemed inappropriate by the investigator
* Presence of ARIA-E findings at the Week 116 MRI scan

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
6/06/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
17/02/2023
Sample size
Target
Accrual to date
Final
1053
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC,WA
Recruitment hospital [1] 0 0
St Vincent's Hospital Sydney; Neurology - Darlinghurst
Recruitment hospital [2] 0 0
Central Coast Neurosciences Research - Erina
Recruitment hospital [3] 0 0
Southern Neurology - Kogarah
Recruitment hospital [4] 0 0
The Queen Elizabeth Hospital; Neurology - Woodville
Recruitment hospital [5] 0 0
Heidelberg Repatriation Hospital; Medical and Cognitive Research Centre - Heidelberg West
Recruitment hospital [6] 0 0
Neuro Trials Victoria - Noble Park
Recruitment hospital [7] 0 0
Australian Alzheimer's Research Foundation - Nedlands
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2250 - Erina
Recruitment postcode(s) [3] 0 0
2217 - Kogarah
Recruitment postcode(s) [4] 0 0
5011 - Woodville
Recruitment postcode(s) [5] 0 0
3081 - Heidelberg West
Recruitment postcode(s) [6] 0 0
3174 - Noble Park
Recruitment postcode(s) [7] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Kansas
Country [9] 0 0
United States of America
State/province [9] 0 0
Mississippi
Country [10] 0 0
United States of America
State/province [10] 0 0
New Jersey
Country [11] 0 0
United States of America
State/province [11] 0 0
New York
Country [12] 0 0
United States of America
State/province [12] 0 0
Ohio
Country [13] 0 0
United States of America
State/province [13] 0 0
Pennsylvania
Country [14] 0 0
United States of America
State/province [14] 0 0
South Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
United States of America
State/province [16] 0 0
Utah
Country [17] 0 0
United States of America
State/province [17] 0 0
Virginia
Country [18] 0 0
United States of America
State/province [18] 0 0
Wisconsin
Country [19] 0 0
Brazil
State/province [19] 0 0
PR
Country [20] 0 0
Brazil
State/province [20] 0 0
RS
Country [21] 0 0
Brazil
State/province [21] 0 0
SP
Country [22] 0 0
Canada
State/province [22] 0 0
British Columbia
Country [23] 0 0
Canada
State/province [23] 0 0
Ontario
Country [24] 0 0
Canada
State/province [24] 0 0
Quebec
Country [25] 0 0
China
State/province [25] 0 0
Beijing City
Country [26] 0 0
China
State/province [26] 0 0
Chengdu
Country [27] 0 0
China
State/province [27] 0 0
Chongqing
Country [28] 0 0
China
State/province [28] 0 0
Fuzhou City
Country [29] 0 0
China
State/province [29] 0 0
Guangzhou City
Country [30] 0 0
China
State/province [30] 0 0
Guangzhou
Country [31] 0 0
China
State/province [31] 0 0
Hangzhou City
Country [32] 0 0
China
State/province [32] 0 0
Hangzhou
Country [33] 0 0
China
State/province [33] 0 0
Hefei
Country [34] 0 0
China
State/province [34] 0 0
Nanchang
Country [35] 0 0
China
State/province [35] 0 0
Nanjing City
Country [36] 0 0
China
State/province [36] 0 0
Nanjing
Country [37] 0 0
China
State/province [37] 0 0
Shanghai City
Country [38] 0 0
China
State/province [38] 0 0
Shanghai
Country [39] 0 0
China
State/province [39] 0 0
Shenzhen City
Country [40] 0 0
China
State/province [40] 0 0
Tianjin
Country [41] 0 0
China
State/province [41] 0 0
Wenzhou
Country [42] 0 0
China
State/province [42] 0 0
Yangzhou City
Country [43] 0 0
China
State/province [43] 0 0
Zhengzhou
Country [44] 0 0
France
State/province [44] 0 0
Amiens Cedex1
Country [45] 0 0
France
State/province [45] 0 0
Bobigny Cedex
Country [46] 0 0
France
State/province [46] 0 0
Bron cedex
Country [47] 0 0
France
State/province [47] 0 0
Marseille
Country [48] 0 0
France
State/province [48] 0 0
Paris
Country [49] 0 0
France
State/province [49] 0 0
Poitiers
Country [50] 0 0
France
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Strasbourg
Country [51] 0 0
France
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Toulouse
Country [52] 0 0
France
State/province [52] 0 0
Villeurbanne
Country [53] 0 0
Germany
State/province [53] 0 0
Berlin
Country [54] 0 0
Germany
State/province [54] 0 0
Bochum
Country [55] 0 0
Germany
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Köln
Country [56] 0 0
Germany
State/province [56] 0 0
Leipzig
Country [57] 0 0
Germany
State/province [57] 0 0
Mainz
Country [58] 0 0
Germany
State/province [58] 0 0
München
Country [59] 0 0
Germany
State/province [59] 0 0
Münster
Country [60] 0 0
Germany
State/province [60] 0 0
Rostock
Country [61] 0 0
Germany
State/province [61] 0 0
Ulm
Country [62] 0 0
Germany
State/province [62] 0 0
Westerstede
Country [63] 0 0
Germany
State/province [63] 0 0
Witten
Country [64] 0 0
Hungary
State/province [64] 0 0
Budapest
Country [65] 0 0
Italy
State/province [65] 0 0
Emilia-Romagna
Country [66] 0 0
Italy
State/province [66] 0 0
Lazio
Country [67] 0 0
Italy
State/province [67] 0 0
Lombardia
Country [68] 0 0
Italy
State/province [68] 0 0
Molise
Country [69] 0 0
Italy
State/province [69] 0 0
Piemonte
Country [70] 0 0
Italy
State/province [70] 0 0
Sicilia
Country [71] 0 0
Japan
State/province [71] 0 0
Chiba
Country [72] 0 0
Japan
State/province [72] 0 0
Fukushima
Country [73] 0 0
Japan
State/province [73] 0 0
Kanagawa
Country [74] 0 0
Japan
State/province [74] 0 0
Niigata
Country [75] 0 0
Japan
State/province [75] 0 0
Shizuoka
Country [76] 0 0
Japan
State/province [76] 0 0
Tochigi
Country [77] 0 0
Japan
State/province [77] 0 0
Tokyo
Country [78] 0 0
Japan
State/province [78] 0 0
Yamagata
Country [79] 0 0
Lithuania
State/province [79] 0 0
Vilnius
Country [80] 0 0
Peru
State/province [80] 0 0
Bellavista
Country [81] 0 0
Peru
State/province [81] 0 0
Lima
Country [82] 0 0
Peru
State/province [82] 0 0
San Martin de Porres
Country [83] 0 0
Russian Federation
State/province [83] 0 0
Krasnojarsk
Country [84] 0 0
Russian Federation
State/province [84] 0 0
Moskovskaja Oblast
Country [85] 0 0
Russian Federation
State/province [85] 0 0
Sankt Petersburg
Country [86] 0 0
Russian Federation
State/province [86] 0 0
Tatarstan
Country [87] 0 0
Russian Federation
State/province [87] 0 0
Saratov
Country [88] 0 0
Russian Federation
State/province [88] 0 0
Tomsk
Country [89] 0 0
Spain
State/province [89] 0 0
Barcelona
Country [90] 0 0
Spain
State/province [90] 0 0
Cantabria
Country [91] 0 0
Spain
State/province [91] 0 0
LA Rioja
Country [92] 0 0
Spain
State/province [92] 0 0
Madrid
Country [93] 0 0
Spain
State/province [93] 0 0
Albacete
Country [94] 0 0
Spain
State/province [94] 0 0
Cordoba
Country [95] 0 0
Spain
State/province [95] 0 0
Salamanca
Country [96] 0 0
Spain
State/province [96] 0 0
Sevilla
Country [97] 0 0
Spain
State/province [97] 0 0
Valencia
Country [98] 0 0
Spain
State/province [98] 0 0
Zaragoza
Country [99] 0 0
Taiwan
State/province [99] 0 0
Changhua County
Country [100] 0 0
Taiwan
State/province [100] 0 0
Kaohsiung
Country [101] 0 0
Taiwan
State/province [101] 0 0
Niaosong Dist.
Country [102] 0 0
Taiwan
State/province [102] 0 0
North Dist.
Country [103] 0 0
Taiwan
State/province [103] 0 0
Taipei
Country [104] 0 0
Taiwan
State/province [104] 0 0
Taoyuan

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT03444870