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)

Alzheimers Disease Clinical Trial

— SKYLINE  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05256134
• Other study ID #: WN42444
• Secondary ID: 2021-001184-25
• Status: Terminated
• Phase: Phase 3
• Start date: April 19, 2022
• Est. completion date: March 10, 2023

Study information

• Verified date: April 2023
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 24
• Est. completion date: March 10, 2023
• Est. primary completion date: March 10, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimers Disease

Intervention

Drug:
• Gantenerumab
Gantenerumab will be administered as per the dosing schedule described in the Arm description.
• Placebo
Placebo will be administered as per the dosing schedule described in the Arm description.

Locations

Country	Name	City	State
Argentina	NeuroSite	Ciudad Autonoma Buenos Aires
Argentina	Instituto Kremer	Córdoba
Argentina	Fundacion Scherbovsky	Mendoza
Australia	Heidelberg Repatriation Hospital; Medical and Cognitive Research Centre	Heidelberg West	Victoria
Australia	KaRa Institute of Neurological Diseases	Macquarie Park	New South Wales
Australia	Australian Alzheimer's Research Foundation	Nedlands	Western Australia
Canada	True North Clinical Research-Halifax	Halifax	Nova Scotia
Canada	Okanagan Clinical Trials	Kelowna	British Columbia
Canada	Kawartha Centre - Redefining Healthy Aging	Peterborough	Ontario
Canada	Alpha Recherche Clinique	Quebec
Canada	Toronto Memory Program	Toronto	Ontario
Italy	IRCCS Ospedale San Raffaele; U.O. di Neurologia	Milano	Lombardia
Italy	AO di Perugia - Ospedale S. Maria della Misericordia; Clinica Neurologica	Perugia	Umbria
Italy	IRCCS Neuromed; Neurologia I-Centro studio e cura delle demenze e UVA	Pozzilli	Molise
Italy	Fondazione Santa Lucia IRCCS; Neurologia e Riabilitazione Neurologica	Roma	Lazio
Italy	Ospedale San Giovanni Calibita Fatebenefratell;Neurologia	Roma	Lazio
Korea, Republic of	Dong-A University Hospital	Busan
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Konkuk University Medical Center	Seoul
Poland	KLIMED	Bia?ystok
Poland	NZOZ Vitamed	Bydgoszcz
Poland	NZOZ NEURO-KARD Ilkowski i Partnerzy Sp. Partn. Lek	Pozna?
Poland	Senior Sp. Z O.O. Poradnia Psychogeriatryczna	Sopot
Poland	Centrum Medyczne Euromedis Sp. z o.o.	Szczecin
Poland	NZOZ WCA	Wroc?aw
Spain	BARCELONABETA BRAIN RESEARCH CENTER (BBRC); FUNDACIÓN PASQUAL MARAGALL, Servicio de Neurologia	Barcelona
Spain	Fundación ACE; Servicio de Neurología	Barcelona
Spain	Hospital Quiron de Madrid; Servicio de Neurologia	Pozuelo de Alarcon	Madrid
Spain	Hospital Virgen del Rocío; Servicio de Neurología	Sevilla
Sweden	Sahlgrenska Academy University,Neuroscience and Physiology;Departmt of Psychiatry and Neurochemistry	Mölndal
Sweden	KAROLINSKA UNI HOSPITAL, HUDDINGE; Mottagning Kognitiv Forskning, M54	Stockholm
United Kingdom	Re-Cognition	Birmingham
United Kingdom	University of Exeter; College of Medicine and Health	Exeter
United Kingdom	Panthera Biopartners Sheffield	Sheffield
United Kingdom	Southampton General Hospital	Southampton
United Kingdom	Victoria Centre; Kingshill Research Centre	Swindon
United States	JEM Research LLC	Atlantis	Florida
United States	Senior Adults Specialty Research	Austin	Texas
United States	Visionary Investigators Network - Neurology Aventura	Aventura	Florida
United States	Bradenton Research Center	Bradenton	Florida
United States	Great Lakes Clinical Trials	Chicago	Illinois
United States	Ohio State University; College of Medicine	Columbus	Ohio
United States	Kerwin Medical Center	Dallas	Texas
United States	Brain Matters Research, Inc.	Delray Beach	Florida
United States	Velocity Clinical Research	East Syracuse	New York
United States	Keystone Clinical Studies LLC	Emmaus	Pennsylvania
United States	Re:Cognition Health	Fairfax	Virginia
United States	Quest Research Institute	Farmington Hills	Michigan
United States	Neuropsychiatric Research; Center of Southwest Florida	Fort Myers	Florida
United States	Center for Advanced Research & Education	Gainesville	Georgia
United States	ClinCloud, LLC	Maitland	Florida
United States	Tandem Clinical Research, LLC	Marrero	Louisiana
United States	Alzheimer's Memory Center	Matthews	North Carolina
United States	Optimus U Corp	Miami	Florida
United States	Renstar Medical Research	Ocala	Florida
United States	University of Nebraska Medical Center; Dept of Neurological Sciences	Omaha	Nebraska
United States	K2 Medical Research, LLC	Orlando	Florida
United States	Banner Alzheimer?s Institute	Phoenix	Arizona
United States	Progressive Medical Research	Port Orange	Florida
United States	Summit Research Network Inc.	Portland	Oregon
United States	California Neuroscience Research Medical Group, Inc	Sherman Oaks	California
United States	The Cognitive and Research Center of New Jersey	Springfield	New Jersey
United States	Alzheimer's Research and Treatment Center	Stuart	Florida
United States	Banner Sun Health Research Insitute	Sun City	Arizona
United States	Charter Research - Lady Lake/The Villages	The Villages	Florida
United States	Banner Alzheimer's Institute	Tucson	Arizona
United States	Alzheimer?s Research and Treatment Center	Wellington	Florida
United States	Premiere Research Institute	West Palm Beach	Florida
United States	Via Christi Research	Wichita	Kansas
United States	Charter Research - Winter Park/Orlando	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Canada,  Italy,  Korea, Republic of,  Poland,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline to Year 4 in Preclinical Alzheimer's Cognitive Composite-5 (PACC-5) Score		Baseline up to Week 211
Secondary	Time from Randomization to Clinical Progression to Mild Cognitive Impairment (MCI) or Dementia due to AD		Baseline up to Week 211
Secondary	Time to Onset of Confirmed Clinical Progression		Baseline up to Week 211
Secondary	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
Secondary	Change from Baseline to Year 4 in the Cognitive Function Instrument Acute (CFIa)		Baseline up to Week 211
Secondary	Change from Baseline to Year 4 in the Clinical Dementia Rating Sum of Boxes (CDR-SB)		Baseline up to Week 211
Secondary	Number of Participants with Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)		Baseline up to Week 211
Secondary	Number of Participants with Anti-Drug Antibodies (ADAs)		Baseline up to Week 211
Secondary	Change in Brain Amyloid Load Over Time in a Subset of Partcipants		Baseline up to Week 211
Secondary	Change in Brain Tau Load Over Time in a Subset of Partcipants		Baseline up to Week 211
Secondary	Change in Cerebrospinal Fluid (CSF) Abeta 1-42 Over Time in a Subset of Participants		Baseline up to Week 211
Secondary	Change in CSF Abeta 1-40 Over Time in a Subset of Partcipants		Baseline up to Week 211
Secondary	Change in CSF Neurofilament Light (NfL) Over Time in a Subset of Participants		Baseline up to Week 211
Secondary	Change in CSF Phosphorylated Tau (pTau) Over Time in a Subset of Participants		Baseline up to Week 211
Secondary	Change in CSF Total Tau (tTau) Over Time in a Subset of Participants		Baseline up to Week 211
Secondary	Change in Blood Abeta 1-42 Over Time		Baseline up to Week 211
Secondary	Change in Blood Abeta 1-40 Over Time		Baseline up to Week 211
Secondary	Change in Blood NfL Over Time		Baseline up to Week 211
Secondary	Change in Blood pTau Over Time		Baseline up to Week 211
Secondary	Change in Whole Brain Volume as Determined by Magnetic Resonance Imaging (MRI)		Baseline up to Week 211
Secondary	Change in Ventricle Volume as Determined by MRI		Baseline up to Week 211
Secondary	Change in Hippocampal Volume as Determined by MRI		Baseline up to Week 211