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)

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

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).

Study Overview

• Status: Terminated
• Conditions: Alzheimers Disease
• Intervention / Treatment: Drug: Gantenerumab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: WN42444 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. and Canada); Email: global-roche-genentech-trials@gene.com

Study Locations

• Argentina
  • Ciudad Autonoma Buenos Aires, Argentina, C1405CBA
    • NeuroSite
  • Córdoba, Argentina, X5004AOA
    • Instituto Kremer
  • Mendoza, Argentina, M5500AYB
    • Fundacion Scherbovsky
• Australia
  • New South Wales
    • Macquarie Park, New South Wales, Australia, 2113
      • KaRa Institute of Neurological Diseases
  • Victoria
    • Heidelberg West, Victoria, Australia, 3081
      • Heidelberg Repatriation Hospital; Medical and Cognitive Research Centre
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Australian Alzheimer's Research Foundation
• Canada
  • Quebec, Canada, G3K 2P8
    • ALPHA Recherche Clinique
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 1Z9
      • Okanagan Clinical Trials
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3S 1N2
      • True North Clinical Research-Halifax
  • Ontario
    • Peterborough, Ontario, Canada, K9H 2P4
      • Kawartha Centre - Redefining Healthy Aging
    • Toronto, Ontario, Canada, M3B 2S7
      • Toronto Memory Program
• Italy
  • Lazio
    • Roma, Lazio, Italy, 00186
      • Ospedale San Giovanni Calibita Fatebenefratell;Neurologia
    • Roma, Lazio, Italy, 00179
      • Fondazione Santa Lucia IRCCS; Neurologia e Riabilitazione Neurologica
  • Lombardia
    • Milano, Lombardia, Italy, 20132
      • IRCCS Ospedale San Raffaele; U.O. di Neurologia
  • Molise
    • Pozzilli, Molise, Italy, 86077
      • IRCCS Neuromed; Neurologia I-Centro studio e cura delle demenze e UVA
  • Umbria
    • Perugia, Umbria, Italy, 06156
      • AO di Perugia - Ospedale S. Maria della Misericordia; Clinica Neurologica
• Korea, Republic of
  • Busan, Korea, Republic of, 49201
    • Dong-a University hospital
  • Incheon, Korea, Republic of, 21565
    • Gachon University Gil Medical Center
  • Seoul, Korea, Republic of, 05030
    • Konkuk University Medical Center
• Poland
  • Bia?ystok, Poland, 15-704
    • KLIMED
  • Bydgoszcz, Poland, 85-079
    • NZOZ Vitamed
  • Pozna?, Poland, 61-853
    • NZOZ NEURO-KARD Ilkowski i Partnerzy Sp. Partn. Lek
  • Sopot, Poland, 81-855
    • Senior Sp. Z O.O. Poradnia Psychogeriatryczna
  • Szczecin, Poland, 70-111
    • Centrum Medyczne Euromedis Sp. z o.o.
  • Wroc?aw, Poland, 53-659
    • NZOZ WCA
• Spain
  • Barcelona, Spain, 08028
    • Fundación ACE; Servicio de Neurología
  • Barcelona, Spain, 08005
    • BARCELONABETA BRAIN RESEARCH CENTER (BBRC); FUNDACIÓN PASQUAL MARAGALL, Servicio de Neurologia
  • Sevilla, Spain, 41013
    • Hospital Virgen del Rocío; Servicio de Neurología
  • Madrid
    • Pozuelo de Alarcon, Madrid, Spain, 28223
      • Hospital Quiron de Madrid; Servicio de Neurologia
• Sweden
  • Mölndal, Sweden, 431 41
    • Sahlgrenska Academy University,Neuroscience and Physiology;Departmt of Psychiatry and Neurochemistry
  • Stockholm, Sweden, 141 86
    • KAROLINSKA UNI HOSPITAL, HUDDINGE; Mottagning Kognitiv Forskning, M54
• United Kingdom
  • Birmingham, United Kingdom, B16 8QQ
    • Re-Cognition
  • Exeter, United Kingdom, EX1 2LU
    • University of Exeter; College of Medicine and Health
  • Sheffield, United Kingdom, S2 5FX
    • Panthera Biopartners Sheffield
  • Southampton, United Kingdom, SO16 6YD
    • Southampton General Hospital
  • Swindon, United Kingdom, SN3 6BW
    • Victoria Centre; Kingshill Research Centre
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner Alzheimer?s Institute
    • Sun City, Arizona, United States, 85351
      • Banner Sun Health Research Insitute
    • Tucson, Arizona, United States, 85718
      • Banner Alzheimer's Institute
  • California
    • Sherman Oaks, California, United States, 91403
      • California Neuroscience Research Medical Group, Inc
  • Florida
    • Atlantis, Florida, United States, 33462
      • JEM Research LLC
    • Aventura, Florida, United States, 33180
      • Visionary Investigators Network - Neurology Aventura
    • Bradenton, Florida, United States, 34205
      • Bradenton Research Center
    • Delray Beach, Florida, United States, 33445
      • Brain Matters Research, Inc.
    • Fort Myers, Florida, United States, 33912
      • Neuropsychiatric Research; Center of Southwest Florida
    • Maitland, Florida, United States, 32751
      • ClinCloud, LLC
    • Miami, Florida, United States, 33125
      • Optimus U Corp
    • Ocala, Florida, United States, 34470
      • Renstar Medical Research
    • Orlando, Florida, United States, 32751
      • K2 Medical Research, LLC
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
    • Stuart, Florida, United States, 34997
      • Alzheimer's Research and Treatment Center
    • The Villages, Florida, United States, 32162
      • Charter Research - Lady Lake/The Villages
    • Wellington, Florida, United States, 33414
      • Alzheimer?s Research and Treatment Center
    • West Palm Beach, Florida, United States, 33407
      • Premiere Research Institute
    • Winter Park, Florida, United States, 32792
      • Charter Research - Winter Park/Orlando
  • Georgia
    • Gainesville, Georgia, United States, 30501
      • Center for Advanced Research & Education
  • Illinois
    • Chicago, Illinois, United States, 60640
      • Great Lakes Clinical Trials
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Via Christi Research
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Tandem Clinical Research, LLC
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Quest Research Institute
  • Nebraska
    • Omaha, Nebraska, United States, 68198-8440
      • University of Nebraska Medical Center; Dept of Neurological Sciences
  • New Jersey
    • Springfield, New Jersey, United States, 07081
      • The Cognitive and Research Center of New Jersey
  • New York
    • East Syracuse, New York, United States, 13057
      • Velocity Clinical Research
  • North Carolina
    • Matthews, North Carolina, United States, 28105
      • Alzheimer's Memory Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University; College of Medicine
  • Oregon
    • Portland, Oregon, United States, 97210
      • Summit Research Network Inc.
  • Pennsylvania
    • Emmaus, Pennsylvania, United States, 18049
      • Keystone Clinical Studies LLC
  • Texas
    • Austin, Texas, United States, 78757
      • Senior Adults Specialty Research
    • Dallas, Texas, United States, 75231
      • Kerwin Medical Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • RE:Cognition Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline to Year 4 in Preclinical Alzheimer's Cognitive Composite-5 (PACC-5) Score	Baseline up to Week 211

Secondary Outcome Measures

Outcome Measure	Time Frame
Time from Randomization to Clinical Progression to Mild Cognitive Impairment (MCI) or Dementia due to AD	Baseline up to Week 211
Time to Onset of Confirmed Clinical Progression	Baseline up to Week 211
Change from Baseline to Year 4 in the Amsterdam Instrumental Activities of Daily Living Questionnaire Short Version (A-IADL-Q-SV)	Baseline up to Week 211
Change from Baseline to Year 4 in the Cognitive Function Instrument Acute (CFIa)	Baseline up to Week 211
Change from Baseline to Year 4 in the Clinical Dementia Rating Sum of Boxes (CDR-SB)	Baseline up to Week 211
Number of Participants with Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)	Baseline up to Week 211
Number of Participants with Anti-Drug Antibodies (ADAs)	Baseline up to Week 211
Change in Brain Amyloid Load Over Time in a Subset of Partcipants	Baseline up to Week 211
Change in Brain Tau Load Over Time in a Subset of Partcipants	Baseline up to Week 211
Change in Cerebrospinal Fluid (CSF) Abeta 1-42 Over Time in a Subset of Participants	Baseline up to Week 211
Change in CSF Abeta 1-40 Over Time in a Subset of Partcipants	Baseline up to Week 211
Change in CSF Neurofilament Light (NfL) Over Time in a Subset of Participants	Baseline up to Week 211
Change in CSF Phosphorylated Tau (pTau) Over Time in a Subset of Participants	Baseline up to Week 211
Change in CSF Total Tau (tTau) Over Time in a Subset of Participants	Baseline up to Week 211
Change in Blood Abeta 1-42 Over Time	Baseline up to Week 211
Change in Blood Abeta 1-40 Over Time	Baseline up to Week 211
Change in Blood NfL Over Time	Baseline up to Week 211
Change in Blood pTau Over Time	Baseline up to Week 211
Change in Whole Brain Volume as Determined by Magnetic Resonance Imaging (MRI)	Baseline up to Week 211
Change in Ventricle Volume as Determined by MRI	Baseline up to Week 211
Change in Hippocampal Volume as Determined by MRI	Baseline up to Week 211

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2022
• Primary Completion (Actual): March 10, 2023
• Study Completion (Actual): March 10, 2023

Study Registration Dates

• First Submitted: January 25, 2022
• First Submitted That Met QC Criteria: February 16, 2022
• First Posted (Actual): February 25, 2022

Study Record Updates

• Last Update Posted (Actual): April 18, 2023
• Last Update Submitted That Met QC Criteria: April 17, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: WN42444; 2021-001184-25 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No