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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05256134




Registration number
NCT05256134
Ethics application status
Date submitted
25/01/2022
Date registered
25/02/2022

Titles & IDs
Public title
A Study to Evaluate the Efficacy and Safety of Gantenerumab in Participants at Risk for or at the Earliest Stages of Alzheimer's Disease (AD)
Scientific title
A Phase III, Multicenter, Randomized, Parallel-Group, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Gantenerumab in Participants at Risk for or at the Earliest Stages of Alzheimer's Disease
Secondary ID [1] 0 0
2021-001184-25
Secondary ID [2] 0 0
WN42444
Universal Trial Number (UTN)
Trial acronym
SKYLINE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimers 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 subcutaneous (SC) injection with gradual uptitration.

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


Treatment: Drugs: Gantenerumab
Gantenerumab will be administered as per the dosing schedule described in the Arm description.

Treatment: Drugs: Placebo
Placebo will be administered as per the dosing schedule described in the Arm description.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in PACC-5 Score
Timepoint [1] 0 0
Baseline to early termination visit (up to 225 days from start of treatment)
Secondary outcome [1] 0 0
Time From Randomization to Clinical Progression to Mild Cognitive Impairment (MCI) or Dementia Due to AD
Timepoint [1] 0 0
Randomization to early termination Visit (up to 225 days from start of treatment)
Secondary outcome [2] 0 0
Time to Onset of Confirmed Clinical Progression
Timepoint [2] 0 0
Randomization to early termination Visit (up to 225 days from start of treatment)
Secondary outcome [3] 0 0
Change From Baseline in the Amsterdam Instrumental Activities of Daily Living Questionnaire Short Version (A-IADL-Q-SV)
Timepoint [3] 0 0
Baseline to early termination visit (up to 225 days from start of treatment)
Secondary outcome [4] 0 0
Change From Baseline in the Cognitive Function Instrument Acute (CFIa) Participant Version
Timepoint [4] 0 0
Baseline to early termination visit (up to 225 days from start of treatment)
Secondary outcome [5] 0 0
Change From Baseline in the CFIa Study Partner Version
Timepoint [5] 0 0
Baseline to early termination visit (up to 225 days from start of treatment)
Secondary outcome [6] 0 0
Change From Baseline in the Clinical Dementia Rating Sum of Boxes (CDR-SB)
Timepoint [6] 0 0
Baseline to early termination visit (up to 225 days from start of treatment)
Secondary outcome [7] 0 0
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs)
Timepoint [7] 0 0
Day 1 to safety follow-up visit (up to 310 days from start of treatment)
Secondary outcome [8] 0 0
Number of Participants With Anti-Drug Antibodies (ADAs) to Gantenerumab
Timepoint [8] 0 0
Day 1 to early termination visit (up to 216 days from start of treatment)
Secondary outcome [9] 0 0
Number of Participants With Magnetic Resonance Imaging (MRI) Findings: Amyloid-related Imaging Abnormalities - Edema/Effusion (ARIA-E) and ARIA-Hemosiderin Deposition (ARIA-H)
Timepoint [9] 0 0
Day 1 to early termination visit (up to 248 days from start of treatment)
Secondary outcome [10] 0 0
Number of Participants With Injection-site Reactions (ISRs)
Timepoint [10] 0 0
Day 1 to safety follow-up visit (up to 310 days from start of treatment)
Secondary outcome [11] 0 0
Number of Participants With Post-baseline Suicidal Behaviors and Ideations as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score
Timepoint [11] 0 0
Day 1 to safety follow-up visit (up to 310 days from start of treatment)
Secondary outcome [12] 0 0
Change in Brain Amyloid Load Over Time as Measured by Amyloid Positron Emission Tomography (PET) in a Subset of Participants
Timepoint [12] 0 0
Baseline
Secondary outcome [13] 0 0
Change in Brain Tau Load Over Time as Measured by Tau PET in a Subset of Participants
Timepoint [13] 0 0
Baseline
Secondary outcome [14] 0 0
Change in Cerebrospinal Fluid (CSF) Amyloid (A) Peptide Beta (ß): Aß 1-42 Over Time in a Subset of Participants
Timepoint [14] 0 0
Baseline
Secondary outcome [15] 0 0
Change in CSF Amyloid Peptide: Aß 1-40 Over Time in a Subset of Participants
Timepoint [15] 0 0
Baseline
Secondary outcome [16] 0 0
Change in CSF Neurofilament Light (NFL) Over Time in a Subset of Participants
Timepoint [16] 0 0
Baseline
Secondary outcome [17] 0 0
Change in CSF Phosphorylated Tau (pTau) Over Time in a Subset of Participants
Timepoint [17] 0 0
Baseline
Secondary outcome [18] 0 0
Change in CSF Total Tau (tTau) Over Time in a Subset of Participants
Timepoint [18] 0 0
Baseline
Secondary outcome [19] 0 0
Change in Whole Brain Volume Over Time as Determined by MRI in a Subset of Participants
Timepoint [19] 0 0
Baseline
Secondary outcome [20] 0 0
Change in Total Ventricular Volume Over Time as Determined by MRI in a Subset of Participants
Timepoint [20] 0 0
Baseline
Secondary outcome [21] 0 0
Change in Hippocampal Volume Over Time as Determined by MRI in a Subset of Participants
Timepoint [21] 0 0
Baseline

Eligibility
Key inclusion criteria
Key

* Willing and able to comply with the study protocol and complete all aspects of the study [including cognitive and functional assessments, physical and neurological examinations, MRI, CSF collection, genotyping, and positron emission tomography (PET) imaging].
* Cognitively unimpaired with a screening clinical dementia rating global score (CDR-GS) of 0, and Repeatable Battery for the Assessment of Neuropsychological Status Delayed Memory Index (RBANS DMI) >=80.
* Evidence of cerebral amyloid accumulation.
* Participants who have an available person (referred to as a "study partner").
* Fluent in the language of the tests used at the study site.
* Adequate visual and auditory acuity, sufficient to perform neuropsychological testing (eye glasses and hearing aids are permitted).
* Agreed not to participate in other interventional research studies for the duration of this trial.
* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 17 weeks after the final dose of study treatment.

Key
Minimum age
60 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Any evidence of an underlying neurological or neurodegenerative condition that may lead to cognitive impairment other than AD.
* Clinical diagnosis of mild cognitive impairment (MCI), prodromal AD, or any form of dementia.
* History or presence of intracranial or intracerebral vascular malformations, aneurysm, subarachnoid hemorrhage, or intracerebral macrohemorrhage.
* History or presence of posterior reversible encephalopathy syndrome.
* History of ischemic stroke with clinical symptoms or an acute event that is consistent with a transient ischemic attack within 12 months of screening.
* History of severe, clinically significant (i.e., resulting in persistent neurologic deficit or structural brain damage) central nervous system (CNS) trauma (e.g., cerebral contusion).
* History or presence of intracranial mass lesion (e.g., glioma, meningioma) that could potentially impair cognition or lead to progressive neurological deficits.
* Infections that may affect brain function or a history of infections that resulted in neurologic sequelae [e.g., human immunodeficiency virus (HIV), syphilis, neuroborreliosis, and viral or bacterial meningitis and encephalitis].
* History of major depression, schizophrenia, schizoaffective disorder, or bipolar disorder.
* At risk for suicide.
* History of alcohol and/or substance abuse or dependence.
* History or presence of clinically significant systemic vascular disease, atrial fibrillation or heart failure.
* Within the last year, experienced unstable or clinically significant cardiovascular disease (e.g., myocardial infarction).
* Uncontrolled hypertension.
* Chronic kidney disease, indicated by creatinine clearance <30 mL/min.
* Confirmed and unexplained impaired hepatic function.
* History of, or are known to currently have an HIV infection, or hepatitis B or hepatitis C virus infection that has not been adequately treated.
* History or presence of systemic autoimmune disorders that may lead to progressive neurological impairment with associated cognitive deficits.
* Systemic immunosuppression or immunomodulation due to the continuing effects of immunosuppressant or immunomodulating medications.
* Current COVID-19 infection.
* Evidence of folic acid or vitamin B-12 deficiency.
* Any passive immunotherapy (Ig) or other long-acting biologic agent to prevent or postpone cognitive decline within 1 year of screening.
* Any other investigational treatment within 5 half-lives or 6 months (whichever is longer) prior to screening.
* Typical/Atypical anti-psychotic medications or neuroleptic medications.
* Anticoagulation medications within 3 months of screening with no plans to initiate any prior to randomization.
* Any previous treatment with cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists are exclusionary at screening.
* Pregnant or breastfeeding, or intending to become pregnant during the study or within 17 weeks after the final dose of gantenerumab.
* Impaired coagulation.
* Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins, including gantenerumab and gantenerumab excipients.
* Participants who reside in a skilled nursing facility such as a convalescent home or long-term care facility.
* Participants who require residence in such facilities during the study may continue in the study and be followed for efficacy and safety, provided that they have a study partner who meets the study partner requirements.

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
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,VIC,WA
Recruitment hospital [1] 0 0
KaRa Institute of Neurological Diseases - Macquarie Park
Recruitment hospital [2] 0 0
Heidelberg Repatriation Hospital; Medical and Cognitive Research Centre - Heidelberg West
Recruitment hospital [3] 0 0
Australian Alzheimer's Research Foundation - Nedlands
Recruitment postcode(s) [1] 0 0
2113 - Macquarie Park
Recruitment postcode(s) [2] 0 0
3081 - Heidelberg West
Recruitment postcode(s) [3] 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
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Kansas
Country [7] 0 0
United States of America
State/province [7] 0 0
Louisiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
Nebraska
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
North Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
Ohio
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
United States of America
State/province [15] 0 0
Virginia
Country [16] 0 0
Argentina
State/province [16] 0 0
Córdoba
Country [17] 0 0
Canada
State/province [17] 0 0
British Columbia
Country [18] 0 0
Canada
State/province [18] 0 0
Nova Scotia
Country [19] 0 0
Canada
State/province [19] 0 0
Ontario
Country [20] 0 0
Italy
State/province [20] 0 0
Lazio
Country [21] 0 0
Italy
State/province [21] 0 0
Lombardia
Country [22] 0 0
Italy
State/province [22] 0 0
Molise
Country [23] 0 0
Italy
State/province [23] 0 0
Umbria
Country [24] 0 0
Korea, Republic of
State/province [24] 0 0
Busan
Country [25] 0 0
Korea, Republic of
State/province [25] 0 0
Incheon
Country [26] 0 0
Korea, Republic of
State/province [26] 0 0
Seoul
Country [27] 0 0
Poland
State/province [27] 0 0
Bia?ystok
Country [28] 0 0
Poland
State/province [28] 0 0
Bydgoszcz
Country [29] 0 0
Poland
State/province [29] 0 0
Pozna?
Country [30] 0 0
Poland
State/province [30] 0 0
Sopot
Country [31] 0 0
Poland
State/province [31] 0 0
Szczecin
Country [32] 0 0
Poland
State/province [32] 0 0
Wroc?aw
Country [33] 0 0
Spain
State/province [33] 0 0
Madrid
Country [34] 0 0
Spain
State/province [34] 0 0
Barcelona
Country [35] 0 0
Spain
State/province [35] 0 0
Sevilla
Country [36] 0 0
Sweden
State/province [36] 0 0
Mölndal
Country [37] 0 0
Sweden
State/province [37] 0 0
Stockholm
Country [38] 0 0
United Kingdom
State/province [38] 0 0
Birmingham
Country [39] 0 0
United Kingdom
State/province [39] 0 0
Exeter
Country [40] 0 0
United Kingdom
State/province [40] 0 0
Sheffield
Country [41] 0 0
United Kingdom
State/province [41] 0 0
Southampton

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.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). 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.