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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) (SKYLINE)

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ClinicalTrials.gov Identifier: NCT05256134
Recruitment Status : Active, not recruiting
First Posted : February 25, 2022
Last Update Posted : December 14, 2022
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Description
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Brief Summary:
A study to evaluate the efficacy and safety of gantenerumab in amyloid-positive, cognitively unimpaired participants at risk for or at the earliest stages of AD. The planned number of participants for this study is approximately 1200 participants randomized in a 1:1 ratio to receive either gantenerumab or placebo (600 participants randomized to gantenerumab and 600 participants randomized to placebo).

Condition or disease Intervention/treatment Phase
Alzheimers Disease Drug: Gantenerumab Drug: Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : April 19, 2022
Estimated Primary Completion Date : March 15, 2023
Estimated Study Completion Date : March 15, 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Gantenerumab
Gantenerumab will be administered as subcutaneous (SC) injection with gradual uptitration.
 Drug: Gantenerumab
Gantenerumab will be administered as per the dosing schedule described in the Arm description.
Placebo Comparator: Placebo
Placebo will be administered as SC injection with gradual uptitration.
 Drug: Placebo
Placebo will be administered as per the dosing schedule described in the Arm description.


Outcome Measures
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Primary Outcome Measures :
  1. Change from Baseline to Year 4 in Preclinical Alzheimer's Cognitive Composite-5 (PACC-5) Score [ Time Frame: Baseline up to Week 211 ]

Secondary Outcome Measures :
  1. Time from Randomization to Clinical Progression to Mild Cognitive Impairment (MCI) or Dementia due to AD [ Time Frame: Baseline up to Week 211 ]
  2. Time to Onset of Confirmed Clinical Progression [ Time Frame: Baseline up to Week 211 ]
  3. Change from Baseline to Year 4 in the Amsterdam Instrumental Activities of Daily Living Questionnaire Short Version (A-IADL-Q-SV) [ Time Frame: Baseline up to Week 211 ]
  4. Change from Baseline to Year 4 in the Cognitive Function Instrument Acute (CFIa) [ Time Frame: Baseline up to Week 211 ]
  5. Change from Baseline to Year 4 in the Clinical Dementia Rating Sum of Boxes (CDR-SB) [ Time Frame: Baseline up to Week 211 ]
  6. Number of Participants with Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) [ Time Frame: Baseline up to Week 211 ]
  7. Number of Participants with Anti-Drug Antibodies (ADAs) [ Time Frame: Baseline up to Week 211 ]
  8. Change in Brain Amyloid Load Over Time in a Subset of Partcipants [ Time Frame: Baseline up to Week 211 ]
  9. Change in Brain Tau Load Over Time in a Subset of Partcipants [ Time Frame: Baseline up to Week 211 ]
  10. Change in Cerebrospinal Fluid (CSF) Abeta 1-42 Over Time in a Subset of Participants [ Time Frame: Baseline up to Week 211 ]
  11. Change in CSF Abeta 1-40 Over Time in a Subset of Partcipants [ Time Frame: Baseline up to Week 211 ]
  12. Change in CSF Neurofilament Light (NfL) Over Time in a Subset of Participants [ Time Frame: Baseline up to Week 211 ]
  13. Change in CSF Phosphorylated Tau (pTau) Over Time in a Subset of Participants [ Time Frame: Baseline up to Week 211 ]
  14. Change in CSF Total Tau (tTau) Over Time in a Subset of Participants [ Time Frame: Baseline up to Week 211 ]
  15. Change in Blood Abeta 1-42 Over Time [ Time Frame: Baseline up to Week 211 ]
  16. Change in Blood Abeta 1-40 Over Time [ Time Frame: Baseline up to Week 211 ]
  17. Change in Blood NfL Over Time [ Time Frame: Baseline up to Week 211 ]
  18. Change in Blood pTau Over Time [ Time Frame: Baseline up to Week 211 ]
  19. Change in Whole Brain Volume as Determined by Magnetic Resonance Imaging (MRI) [ Time Frame: Baseline up to Week 211 ]
  20. Change in Ventricle Volume as Determined by MRI [ Time Frame: Baseline up to Week 211 ]
  21. Change in Hippocampal Volume as Determined by MRI [ Time Frame: Baseline up to Week 211 ]

Eligibility Criteria
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Ages Eligible for Study:   60 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • 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 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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05256134


Locations
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Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
More Information
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT05256134    
Other Study ID Numbers: WN42444
2021-001184-25 ( EudraCT Number )
First Posted: February 25, 2022    Key Record Dates
Last Update Posted: December 14, 2022
Last Verified: December 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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).

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
 Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders