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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03444870
Ethics application status
Date submitted
19/02/2018
Date registered
23/02/2018
Date last updated
17/06/2020

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
Change From Baseline to Week 116 in Global Outcome, as Measured by Clinical Dementia Rating-Sum of Boxes (CDR-SOB)
Timepoint [1] 0 0
Baseline Up to Week 116
Secondary outcome [1] 0 0
Change from Baseline to Week 116 in Mini-Mental State Examination (MMSE) Total Score
Timepoint [1] 0 0
Baseline Up to Week 116
Secondary outcome [2] 0 0
Change from Baseline to Week 116 in Alzheimer Disease Assessment Scale-Cognition, Subscale 11 (ADAS-Cog11)
Timepoint [2] 0 0
Baseline Up to Week 116
Secondary outcome [3] 0 0
Change from Baseline to Week 116 in Alzheimer Disease Assessment Scale-Cognition, Subscale 13 (ADAS-Cog13)
Timepoint [3] 0 0
Baseline Up to Week 116
Secondary outcome [4] 0 0
Change from Baseline to Week 116 in Verbal Fluency Task Score
Timepoint [4] 0 0
Baseline Up to Week 116
Secondary outcome [5] 0 0
Change from Baseline to Week 116 in Coding
Timepoint [5] 0 0
Change from baseline to Week 116 in the Wechsler Adult Intelligence Scale - Fourth Edition (WAIS-IV) coding subtest.
Secondary outcome [6] 0 0
Change from Baseline to Week 116 in Functional Activities Questionnaire (FAQ) Score
Timepoint [6] 0 0
Baseline Up to Week 116
Secondary outcome [7] 0 0
Change from Baseline to Week 116 in Alzheimer Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) Total Score
Timepoint [7] 0 0
Baseline Up to Week 116
Secondary outcome [8] 0 0
Percentage of Participants with Adverse Events
Timepoint [8] 0 0
Baseline up to end of study (week 164) or Week 35 (Open label extension)
Secondary outcome [9] 0 0
Change in Columbia-Suicide Severity Rating Scale (C-SSRS) Score
Timepoint [9] 0 0
Baseline up to Week 116 or Week 24 in Open label extension
Secondary outcome [10] 0 0
Percentage of Participants with Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Confirmed by Magnetic Resonance Imaging (MRI)
Timepoint [10] 0 0
Baseline up to end of study (week 164) or Week 35 (Open label extension)
Secondary outcome [11] 0 0
Percentage of Participants with Amyloid-Related Imaging Abnormalities-Haemosiderin deposition (ARIA-H) Confirmed by Magnetic Resonance Imaging (MRI)
Timepoint [11] 0 0
Baseline up to end of study (week 164) or Week 35 (Open label extension)
Secondary outcome [12] 0 0
Percentage of Participants with Injection-Site Reactions
Timepoint [12] 0 0
Baseline up to end of study (week 164) or Week 35 (Open label extension)
Secondary outcome [13] 0 0
Percentage of Participants With Anti-drug Antibody (ADA) to Gantenerumab
Timepoint [13] 0 0
Baseline up to end of study (week 164) or Week 35 (Open label extension)
Secondary outcome [14] 0 0
Plasma Concentration of Gantenerumab Administered SC
Timepoint [14] 0 0
Baseline, Week 2, 24, 41, 52, 76, 103, 115, 128, 164 and at early termination and unscheduled visit, Week 1 and Week 24 (Open label extension)
Secondary outcome [15] 0 0
Change from Baseline in Brain Amyloid Load as Measured by Amyloid Positron Emission Tomography (PET) Scan in a subset of patients up to Week 116
Timepoint [15] 0 0
Baseline Up to Week 116
Secondary outcome [16] 0 0
Change from Baseline in Brain Tau Load as Measured by Tau PET Scan in a subset of patients up to Week 116
Timepoint [16] 0 0
Baseline Up to Week 116
Secondary outcome [17] 0 0
Change From Baseline in Cerebral Spinal Fluid (CSF) Marker of Disease in a subset of patients - Amyloidbeta 1-42 (Aß1-42) up to Week 116
Timepoint [17] 0 0
Baseline Up to Week 116
Secondary outcome [18] 0 0
Change From Baseline in CSF Marker of Disease in a subset of patients - Total Tau up to Week 116
Timepoint [18] 0 0
Baseline Up to Week 116
Secondary outcome [19] 0 0
Change From Baseline in CSF Marker of Disease in a subset of patients - Phosphorylated Tau up to Week 116
Timepoint [19] 0 0
Baseline Up to Week 116
Secondary outcome [20] 0 0
Change From Baseline in Volumetric Magnetic Resonance Imaging (MRI) up to Week 116 - MRI will be used to assess the effect of treatment on volume of whole brain, ventricles, hippocampus, or other structures
Timepoint [20] 0 0
Baseline Up to Week 116

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
Gender
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 104 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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,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
Calvary Mater Newcastle - Waratah
Recruitment hospital [5] 0 0
Queensland University of Technology - Mermaid Waters
Recruitment hospital [6] 0 0
The Queen Elizabeth Hospital; Neurology - Woodville
Recruitment hospital [7] 0 0
Peninsula Therapeutic & Research Group - Frankston
Recruitment hospital [8] 0 0
Heidelberg Repatriation Hospital; Medical and Cognitive Research Centre - Heidelberg West
Recruitment hospital [9] 0 0
HammondCare Aged Psychiatry Clinical Trials - Malvern
Recruitment hospital [10] 0 0
Neuro Trials Victoria - Noble Park
Recruitment hospital [11] 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
2298 - Waratah
Recruitment postcode(s) [5] 0 0
4218 - Mermaid Waters
Recruitment postcode(s) [6] 0 0
5011 - Woodville
Recruitment postcode(s) [7] 0 0
3199 - Frankston
Recruitment postcode(s) [8] 0 0
3081 - Heidelberg West
Recruitment postcode(s) [9] 0 0
3144 - Malvern
Recruitment postcode(s) [10] 0 0
3174 - Noble Park
Recruitment postcode(s) [11] 0 0
6009 - Nedlands
Recruitment outside Australia
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Oregon
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Rostock
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Siegen
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Ulm
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Liguria
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Molise
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Piemonte
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Sicilia
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Chiba
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Lima
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Moskovskaja Oblast
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Cantabria
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Girona
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Madrid
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Valencia
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Zaragoza
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Taiwan
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Changhua County
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Kaohsiung
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Niaosong Dist.
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Taichung
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Taipei
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Taiwan
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Taoyuan

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

Ethics approval
Ethics application status

Summary
Brief summary
This randomized, double-blind, placebo-controlled, parallel-group study will evaluate the
efficacy and safety of gantenerumab versus placebo in participants with early (prodromal to
mild) AD. All participants must show evidence of beta-amyloid pathology. Eligible
participants will be randomized 1:1 to receive either subcutaneous (SC) injection of
gantenerumab or placebo. The primary efficacy assessment will be performed at the end of the
double blind period at week 116. Participants will then be offered to enter into an
open-label extension (OLE). Participants not willing to go to the OLE will participate in a
long term follow-up period for up to 50 weeks after the last gantenerumab dose.
Trial website
https://clinicaltrials.gov/show/NCT03444870
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
Reference Study ID Number: WN29922 www.roche.com/about_roche/roche_worldwide.htm
Address 0 0
Country 0 0
Phone 0 0
888-662-6728 (U.S. and Canada)
Fax 0 0
Email 0 0
Global-Roche-Genentech-Trials@gene.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03444870