Clinical trial NCT06335173: A Study to Evaluate Efficacy and Safety of Intravenous Sabirnetug in Participants with Early Alzheimer's Disease (ALTITUDE-AD)
Official title: A Phase 2 Double-Blind, Randomized, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Intravenous Sabirnetug in Early Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Alzheimer Disease
Keywords: Mild Cognitive Impairment
MCI
Mild Alzheimer's Disease
Memory Loss
Memory Problems
Lead sponsor: Acumen Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2024-03-28
Enrollment: 540
Sex: ALL
Minimum age (years): 50
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study is to evaluate the efficacy of sabirnetug infusions administered once every four weeks (Q4W) in slowing cognitive and functional decline as compared to placebo in participants with early Alzheimer's disease.


Eligibility criteria: Inclusion Criteria:

* Body weight of at least 30 kilograms (kg) (66 pounds \[lbs\]) and no more than 160 kg (352 lbs) at Screening
* Must consent to apolipoprotein E4 (APOE4) genotype status assessment
* Must meet all of the following criteria

  1. National Institute on Aging-Alzheimer's Association (NIA-AA) criteria for mild cognitive impairment (MCI) due to Alzheimer's Disease (AD) or probable AD
  2. Screening score between 22 and 30 (inclusive) on the Mini-Mental State Examination (MMSE)
  3. Screening score of 0.5 or 1.0 on the Clinical Dementia Rating Global Score (CDR-GS) and Screening score ≥0.5 on the CDR Memory Box score
  4. Evidence of cerebral amyloid accumulation by either PET scan or CSF
* If using cholinesterase inhibitors or memantine to treat symptoms related to AD, doses must be stable for at least three months (12 weeks) prior to Baseline and every attempt should be made to keep them at stable doses throughout the study
* Must have a reliable informant or study partner who is willing and able to perform all the roles as specified in the study partner Informed Consent Form (ICF)
* Female participants must be surgically sterile or be at least one-year post-menopausal. Male participants with a female partner of child-bearing potential must use adequate contraception

Exclusion Criteria:

* Has any contraindications for MRI studies, including claustrophobia, the presence of metal (ferromagnetic) implants, or a cardiac pacemaker that is not compatible with MRI
* MRI of the brain that is inconsistent with MCI or AD or results showing greater than four ARIA-H, presence of any ARIA-E, or superficial siderosis
* History of significant or unstable neurological disease, other than AD, which may affect cognition or ability to complete the study, such as other dementias, serious infection of the brain, significant head trauma, uncontrolled seizures, stroke, or Parkinson´s disease
* Current serious or unstable clinically important illness that, in the judgment of the site investigator, is likely to affect cognitive assessment including visual and hearing impairment or affect the participant's safety or ability to complete the study
* Malignant disease in the last five years except for resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ prostate cancer with a normal posttreatment prostate-specific antibody (PSA)
* Geriatric Depression Scale-Short Form (GDS-SF) score \>10 or current symptoms meeting Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V), criteria for major depressive disorder or any current primary psychiatric diagnosis other than AD if, in the judgment of the site investigator, the psychiatric disorder or symptom is likely to confound interpretation of drug effect, affect cognitive assessments, or affect the participant´s ability to complete the study
* Suicide risk, as determined by meeting any of the following criteria:

  1. Any suicide attempt or preparatory acts/behavior on the C-SSRS Baseline/Screening in the last six months
  2. Suicidal ideation in the last six months as defined by a positive response to Question 5 (Suicidal Ideation) on the C-SSRS Baseline/Screening
  3. Significant risk of suicide, as judged by the site investigator
* Conditions that may affect cognitive assessments during the study
* Alcohol use disorder and/or substance use disorder within the last five years

Primary outcomes:
measure: Change from Baseline in Integrated Alzheimer's Disease Rating Scale (iADRS) Score
timeFrame: Baseline up to Week 80
Secondary outcomes:
measure: Change from Baseline in ADCS-iADL Score
timeFrame: Baseline up to Week 80
measure: Change from Baseline in ADAS-Cog13 Score
timeFrame: Baseline up to Week 80
measure: Change from Baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB)
timeFrame: Baseline up to Week 80
measure: Change from Baseline in Mini-Mental State Examination (MMSE)
timeFrame: Baseline up to Week 80
measure: Change from Baseline in Quality of Life in Alzheimer's Disease (QoL-AD)
timeFrame: Baseline up to Week 80
measure: Change from Baseline in Neuropsychiatric Inventory Questionnaire (NPI-Q) Score
timeFrame: Baseline up to Week 80
measure: Change from Baseline in EuroQoL 5-Dimension 5-Level (EQ-5D-5L)
timeFrame: Baseline up to Week 80
measure: Change from Baseline in Resource Utilization in Dementia (RUD)
timeFrame: Baseline up to Week 80
measure: Change from Baseline in Zarit Burden Interview (ZBI)
timeFrame: Baseline up to Week 80
measure: Effect of sabirnetug on Clinical Progression as Compared to Placebo Assessed Using Time Saved Analysis as Measured by iADRS
timeFrame: Baseline up to Week 80
measure: Effect of sabirnetug on Clinical Progression as Compared to Placebo Assessed Using Time Saved Analysis as Measured by ADCS-iADL
timeFrame: Baseline up to Week 80
measure: Effect of sabirnetug on Clinical Progression as Compared to Placebo Assessed Using Time Saved Analysis as Measured by ADAS-Cog13
timeFrame: Baseline up to Week 80
measure: Effect of sabirnetug on Clinical Progression as Compared to Placebo Assessed Using Time Saved Analysis as Measured by CDR-SB
timeFrame: Baseline up to Week 80
measure: Effect of sabirnetug on Clinical Progression as Compared to Placebo Assessed Using Time Saved Analysis as Measured by MMSE
timeFrame: Baseline up to Week 80
measure: Percentage of Participants with No Clinical Progression at One Year
timeFrame: Baseline up to Week 80
measure: Number of Participants with Treatment-Related Adverse Events (TEAEs)
timeFrame: Baseline up to Week 80
measure: Number of Participants with Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI)
timeFrame: Baseline up to Week 80
measure: Number of Participants who Discontinue or Withdraw due to TEAE
timeFrame: Baseline up to Week 80
measure: Number of Participants with Anti-Drug Antibodies (ADA) and Neutralizing Antibodies
timeFrame: Baseline up to Week 80
measure: Number of Participants with Amyloid-Related Imaging Abnormality with Edema/Effusions (ARIA-E) and ARIA with Hemorrhage/Hemosiderin Deposition (ARIA-H) as Measured by Magnetic Resonance Imaging (MRI)
timeFrame: Baseline up to Week 80
measure: Number of Participants with Suicidal Ideation and Behavior as Measured by Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline up to Week 80
measure: Serum Concentration of sabirnetug
timeFrame: Pre-dose and multiple timepoints post dose up to 80 weeks
measure: Concentration of sabirnetug in Cerebrospinal Fluid (CSF)
timeFrame: Up to Week 76
measure: CSF Concentrations of ACU193 in a Subset of Participants
timeFrame: Up to Week 76
measure: Correlation Between sabirnetug Exposure with Clinical Efficacy Measures
timeFrame: Baseline up to 80 weeks
measure: Change From Baseline in Amyloid Plaque Load or Deposition Measured by Positron Emission Tomography (PET) in Centiloids
timeFrame: Baseline up to Week 76
measure: Change from Baseline in Volumetric Magnetic Resonance Imaging (vMRI) of Whole Brain Volume, Ventricular Volume, and Volume of Selected Regions of Interest
timeFrame: Baseline up to Week 76
measure: Target Engagement Assessed by Measurement of sabirnetug- Amyloid-β oligomer (AβO) Complex in CSF
timeFrame: Up to Week 76
measure: Change from Baseline in CSF Concentrations of Amyloid, Tau and Other Neurodegenerative Biomarkers
timeFrame: Baseline up to Week 76
measure: Change from Baseline in CSF Concentrations of Amyloid, Tau, and Other Neurodegenerative Biomarkers in a Subset of Participants
timeFrame: Baseline up to Week 76
measure: Change from Baseline in Blood Concentrations of Amyloid, Tau, and Other Neurodegenerative Biomarkers
timeFrame: Baseline up to Week 76
measure: Correlation Between Change in Biomarker that Reflect Disease Progression and Clinical Changes
timeFrame: Up to 80 weeks
Other outcomes:
Locations:
city: Carlsbad
country: United States
facility: The Neurology Center of Southern California - Carlsbad
state: California
city: Fullerton
country: United States
facility: Neurology Center of North Orange County
state: California
city: Irvine
country: United States
facility: Irvine Medical Research
state: California
city: Long Beach
country: United States
facility: Healthy Brain Research
state: California
city: Santa Ana
country: United States
facility: Syrentis Clinical Research
state: California
city: Sherman Oaks
country: United States
facility: CenExel - California Neuroscience Research Medical Group, Inc (CNR)
state: California
city: New Haven
country: United States
facility: Yale School of Medicine - Alzheimer's Disease Research Unit (ADRU)
state: Connecticut
city: Norwalk
country: United States
facility: Research Center for Clinical Studies, LLC
state: Connecticut
city: Washington
country: United States
facility: Re:Cognition Health - Fairfax
state: District of Columbia
city: Atlantis
country: United States
facility: JEM Research Institute
state: Florida
city: Bradenton
country: United States
facility: Bradenton Research Center
state: Florida
city: Coral Gables
country: United States
facility: Gil Fernandez-Yera, MD, PA
state: Florida
city: Delray Beach
country: United States
facility: Brain Matters Research
state: Florida
city: Homestead
country: United States
facility: Coral Clinical Research
state: Florida
city: Lady Lake
country: United States
facility: K2 Medical Research - Villages
state: Florida
city: Miami
country: United States
facility: Finlay Medical Research
state: Florida
city: Naples
country: United States
facility: Collier Neurologic Specialists (CNS), L.L.C.
state: Florida
city: Ocala
country: United States
facility: Ocala Health - Family Care Specialists - Ocala I
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: Stuart
country: United States
facility: Alzheimer's Research and Treatment Center - Stuart
state: Florida
city: Tampa
country: United States
facility: K2 Medical Research - Tampa
state: Florida
city: The Villages
country: United States
facility: Charter Research - Lady Lake
state: Florida
city: Wellington
country: United States
facility: Alzheimers Research and Treatment Center - Wellington
state: Florida
city: Winter Park
country: United States
facility: Conquest Research
state: Florida
city: Winter Park
country: United States
facility: Charter Research - Winter Park
state: Florida
city: Columbus
country: United States
facility: Columbus Memory Center
state: Georgia
city: Decatur
country: United States
facility: Accel Research- Neurostudies
state: Georgia
city: Decatur
country: United States
facility: CenExel - iResearch Atlanta
state: Georgia
city: Savannah
country: United States
facility: CenExel - iResearch Savannah
state: Georgia
city: Northbrook
country: United States
facility: Office of Jeffrey S. Ross, MD
state: Illinois
city: Newton
country: United States
facility: Boston Center for Memory
state: Massachusetts
city: Hattiesburg
country: United States
facility: Hattiesburg Clinic - Memory Center
state: Mississippi
city: Las Vegas
country: United States
facility: Las Vegas Medical Research Center
state: Nevada
city: Portsmouth
country: United States
facility: ActivMed Practices and Research
state: New Hampshire
city: Princeton
country: United States
facility: Princeton Psychiatric Center
state: New Jersey
city: Springfield
country: United States
facility: The Cognitive and Research Center of New Jersey
state: New Jersey
city: Toms River
country: United States
facility: CenExel - Advanced Memory Research Institute of NJ
state: New Jersey
city: Albuquerque
country: United States
facility: IMA Clinical Research - Albuquerque
state: New Mexico
city: Albany
country: United States
facility: Neurological Associates of Albany
state: New York
city: New York
country: United States
facility: Neurological Institute of New York
state: New York
city: Matthews
country: United States
facility: AMC Research
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: Summit Research Network
state: Oregon
city: Abington
country: United States
facility: Abington Neurological Associates
state: Pennsylvania
city: Norristown
country: United States
facility: Keystone Clinical Research
state: Pennsylvania
city: East Providence
country: United States
facility: Rhode Island Mood and Memory
state: Rhode Island
city: Cordova
country: United States
facility: Neurology Clinic. P.C
state: Tennessee
city: Knoxville
country: United States
facility: The Alliance for Multispecialty Research LLC (AMR)
state: Tennessee
city: Austin
country: United States
facility: Senior Adult Specialty Research
state: Texas
city: Beaumont
country: United States
facility: Gadolin Research, LLC
state: Texas
city: Dallas
country: United States
facility: Kerwin Medical Center
state: Texas
city: Kelowna
country: Canada
facility: Okanagan Clinical Trials
state: British Columbia
city: Ottawa
country: Canada
facility: Hippocampe d/b/a Ottawa Memory Clinic
state: Ontario
city: Peterborough
country: Canada
facility: The Kawartha Regional Memory Clinic (KRMC)
state: Ontario
city: Toronto
country: Canada
facility: Toronto Memory Program (TMP) (Neurology Research Inc.)
state: Ontario
city: Greenfield Park
country: Canada
facility: MoCA Research and Innovations
state: Quebec
city: Bordeaux
country: France
facility: Chu Pellegrin
city: Bron
country: France
facility: Hopital Neurologique Pierre Wertheimer
city: Marseille Cedex 05
country: France
facility: Hôpital de la Timone
city: Montpellier
country: France
facility: Chu Montpellier
city: Paris
country: France
facility: Hopital Lariboisiere
city: Paris
country: France
facility: Institut de la Mémoire et de la Maladie d'Alzheimer -IM2A
city: Rennes
country: France
facility: CHU de Rennes, CMRR
city: Saint-Herblain
country: France
facility: CHU de NANTES-Hôpital Nord Laennec
city: Strasbourg
country: France
facility: Hôpitaux Universitaires de Strasbourg
city: Toulouse
country: France
facility: Centre de Recherche du Gérontopôle - CHU de Toulouse Hôpital la Grave
city: Berlin
country: Germany
facility: Charité - Universitaetsmedizin Berlin
city: Chemnitz
country: Germany
facility: Pharmakologisches Studienzentrum Chemnitz GmbH
city: Cologne
country: Germany
facility: University Hospital of Cologne
city: Homburg
country: Germany
facility: Saarland University Hospital
city: Mannheim
country: Germany
facility: Zentralinstitut für seelische Gesundheit
city: Munich
country: Germany
facility: Technical University of Munich, School of Medicine and Health, Klinikum rechts der Isar
city: Rostock
country: Germany
facility: Rostock University Medical Center
city: Westerstede
country: Germany
facility: Praxisgemeinschaft Dr. Springub/Schwarz
city: Sant Cugat Del Vallès
country: Spain
facility: Hospital Universitari General de catalunya
state: Barcelona
city: San Sebastián
country: Spain
facility: Fundacion CITA alzheimer
state: Gipuzkoa
city: Cuarte de Huerva
country: Spain
facility: Fundacion Neuropolis - Hospital Viamed Montecanal
state: Zaragoza
city: Barcelona
country: Spain
facility: Fundacio ACE
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Getxo
country: Spain
facility: Cae Oroitu
city: Madrid
country: Spain
facility: Hospital Ruber
city: San Sebastian
country: Spain
facility: Policlínica Gipuzkoa
city: Sevilla
country: Spain
facility: Hospital Victoria Eugenia
city: Valencia
country: Spain
facility: Hospital Universitari i Politècnic La Fe
city: London
country: United Kingdom
facility: Re:Cognition Health - London
state: Greater London
city: London
country: United Kingdom
facility: St. Pancras Clinical Research Ltd.
state: Greater London
city: Rochdale
country: United Kingdom
facility: Panthera Bio-Partners - Rochdale
state: Greater Manchester
city: Winchester
country: United Kingdom
facility: Re:Cognition Health - Winchester
state: Hampshire
city: Motherwell
country: United Kingdom
facility: Neuroclin Glasgow
state: Lanarkshire
city: Preston
country: United Kingdom
facility: Panthera Bio-Partners - Preston
state: Lancashire
city: Guildford
country: United Kingdom
facility: Re:Cognition Health - Guildford
state: Surrey
city: Sheffield
country: United Kingdom
facility: Panthera Biopartners - Sheffield
state: Yorkshire
city: Bristol
country: United Kingdom
facility: Re:Cognition Health - Bristol
Study officials:
References: