A Study to Evaluate Efficacy and Safety of Intravenous Sabirnetug in Participants With Early Alzheimer's Disease (ALTITUDE-AD) (ALTITUDE-AD)

A Phase 2 Double-Blind, Randomized, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Intravenous Sabirnetug in Early Alzheimer's Disease

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: Placebo; Drug: sabirnetug

• Study Type: Interventional
• Enrollment (Actual): 542
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Kelowna, British Columbia, Canada
      • Okanagan Clinical Trials
  • Ontario
    • Ottawa, Ontario, Canada
      • Hippocampe d/b/a Ottawa Memory Clinic
    • Toronto, Ontario, Canada
      • Toronto Memory Program (TMP) (Neurology Research Inc.)
  • Quebec
    • Greenfield Park, Quebec, Canada
      • MoCA Research and Innovations
• Germany
  • Berlin, Germany
    • Charité - Universitaetsmedizin Berlin
  • Cologne, Germany
    • University Hospital of Cologne
  • Mannheim, Germany
    • Zentralinstitut für Seelische Gesundheit
  • Munich, Germany
    • Technical University of Munich, School of Medicine and Health, Klinikum rechts der Isar
• Spain
  • Barcelona, Spain
    • Fundació ACE
  • Donostia / San Sebastian, Spain
    • Policlinica Gipuzkoa
  • Getxo, Spain
    • Cae Oroitu
  • Madrid, Spain
    • Hospital Ruber
  • Seville, Spain
    • Hospital Victoria Eugenia
  • Valencia, Spain
    • Hospital Universitari i Politecnic La Fe
  • Barcelona
    • Sant Cugat del Vallès, Barcelona, Spain
      • Hospital Universitari General de Catalunya
  • Zaragoza
    • Cuarte de Huerva, Zaragoza, Spain
      • Fundacion Neuropolis - Hospital Viamed Montecanal
• United Kingdom
  • Bristol, United Kingdom
    • Re:Cognition Health - Bristol
  • Greater London
    • London, Greater London, United Kingdom
      • Re:Cognition Health - London
    • London, Greater London, United Kingdom
      • St. Pancras Clinical Research Ltd.
  • Hampshire
    • Winchester, Hampshire, United Kingdom
      • Re:Cognition Health - Winchester
  • Lanarkshire
    • Motherwell, Lanarkshire, United Kingdom
      • NeuroClin Glasgow
  • Lancashire
    • Preston, Lancashire, United Kingdom
      • Panthera Bio-Partners - Preston
  • Surrey
    • Guildford, Surrey, United Kingdom
      • Re:Cognition Health - Guildford
  • Yorkshire
    • Sheffield, Yorkshire, United Kingdom
      • Panthera Biopartners - Sheffield
• United States
  • California
    • Carlsbad, California, United States, 92011-4219
      • The Neurology Center of Southern California - Carlsbad
    • Fullerton, California, United States, 92835
      • Neurology Center of North Orange County
    • Irvine, California, United States, 92614
      • Irvine Medical Research
    • Long Beach, California, United States, 90804
      • Healthy Brain Research
    • Santa Ana, California, United States, 92705
      • Syrentis Clinical Research
    • Sherman Oaks, California, United States, 91403-2131
      • CenExel - California Neuroscience Research Medical Group, Inc (CNR)
  • Connecticut
    • Norwalk, Connecticut, United States, 06851-4903
      • Research Center for Clinical Studies, LLC
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 22031
      • Re:Cognition Health - Fairfax
  • Florida
    • Atlantis, Florida, United States, 33462
      • JEM Research Institute
    • Bradenton, Florida, United States, 34205
      • Bradenton Research Center
    • Coral Gables, Florida, United States, 33135
      • Gil Fernandez-Yera, MD, PA
    • Delray Beach, Florida, United States, 33445
      • Brain Matters Research
    • Homestead, Florida, United States, 33032
      • Coral Clinical Research
    • Lady Lake, Florida, United States, 32159
      • K2 Medical Research - Villages
    • Miami, Florida, United States, 33126
      • Finlay Medical Research
    • Naples, Florida, United States, 34105-8522
      • Aqualane Clinical Research
    • Ocala, Florida, United States, 34470
      • Ocala Health - Family Care Specialists - Ocala I
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
    • Stuart, Florida, United States, 34997
      • Alzheimer's Research and Treatment Center - Stuart
    • Tampa, Florida, United States, 33607
      • K2 Medical Research - Tampa
    • The Villages, Florida, United States, 32162
      • Charter Research - Lady Lake
    • Wellington, Florida, United States, 33414
      • Alzheimers Research and Treatment Center - Wellington
    • Winter Park, Florida, United States, 32789
      • Conquest Research
    • Winter Park, Florida, United States, 32792
      • Charter Research - Winter Park
  • Georgia
    • Columbus, Georgia, United States, 31909
      • Columbus Memory Center
    • Decatur, Georgia, United States, 30030
      • CenExel - iResearch Atlanta
  • Illinois
    • Northbrook, Illinois, United States, 60640
      • Office of Jeffrey S. Ross, MD
  • Massachusetts
    • Newton, Massachusetts, United States, 02459
      • Boston Center for Memory
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39401-7246
      • Hattiesburg Clinic - Memory Center
  • New Hampshire
    • Portsmouth, New Hampshire, United States, 03801
      • ActivMed Practices and Research
  • New Jersey
    • Springfield, New Jersey, United States, 07081
      • The Cognitive and Research Center of New Jersey
    • Toms River, New Jersey, United States, 08755
      • CenExel - Advanced Memory Research Institute of NJ
  • New York
    • Albany, New York, United States, 12208
      • Neurological Associates of Albany
  • North Carolina
    • Matthews, North Carolina, United States, 28105
      • AMC Research
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Oregon
    • Portland, Oregon, United States, 97210
      • Summit Research Network
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Neurological Associates
    • Norristown, Pennsylvania, United States, 19462
      • Keystone Clinical Research
  • Rhode Island
    • East Providence, Rhode Island, United States, 02914
      • Rhode Island Mood and Memory
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Neurology Clinic. P.C
    • Knoxville, Tennessee, United States, 37920-1511
      • The Alliance for Multispecialty Research LLC (AMR)
  • Texas
    • Austin, Texas, United States, 78757
      • Senior Adult Specialty Research
    • Beaumont, Texas, United States, 77702
      • Gadolin Research, LLC
    • Dallas, Texas, United States, 75231
      • Kerwin Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Double-blind Treatment (DBT) Period: sabirnetug 35 mg/kg; Participants will receive sabirnetug, 35 milligrams per kilogram (mg/kg), Q4W as intravenous (IV) infusion during the DBT period.	Drug: sabirnetug; Intravenous sabirnetug
Experimental: DBT Period: sabirnetug 50 mg/kg; Participants will receive sabirnetug, 35 mg/kg, for the first two doses, followed by sabirnetug, 50 mg/kg, Q4W as an IV infusion during the DBT period.	Drug: sabirnetug; Intravenous sabirnetug
Placebo Comparator: DBT Period: Placebo; Participants will receive sabirnetug matching placebo, Q4W as an IV infusion during the DBT period.	Drug: Placebo; Intravenous Placebo
Experimental: Open-Label Extension (OLE) Period: sabirnetug 35 mg/kg; Participants will receive sabirnetug, 35 mg/kg, Q4W as an IV infusion during the OLE period.	Drug: sabirnetug; Intravenous sabirnetug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Integrated Alzheimer's Disease Rating Scale (iADRS) Score	iADRS is a validated composite of cognition and function made up of Alzheimer's Disease Assessment Scale - Cognitive Subscale 13-item (ADAS-Cog13) and the Alzheimer's Disease Cooperative Study - instrumental Activities of Daily Living scale (ADCS-iADL). ADAS-Cog13 is a rater-administered instrument consisting of 13 items assessing cognitive function areas most typically impaired in AD. ADAS-Cog13 scores range from 0 to 85, with higher scores indicating a greater deficit of global cognition. The ADCS-iADL is a subset of the 23-item ADCS-ADL (items 6a and 7 to 23). The iADLs are more complex skills required to successfully live independently. iADL-items score ranges from 0 to 59 (lower scores indicating greater impairment). The iADRS is calculated as a linear combination of total scores from the ADAS-Cog13 and ADCS-iADL. The iADRS score ranges from 0 to 144 with lower scores indicating worse performance.	Baseline up to Week 80

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in ADCS-iADL Score	The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire to be answered by a participant's study partner, where a participant's performance level is rated over the last 4 weeks, based on a set of performance descriptions. The ADCS-iADL is a subset of the 23-item ADCS-ADL (items 6a and 7 to 23). The iADLs are more complex skills required to successfully live independently, and include shopping, keeping appointments, traveling outside of the home, making a meal or snack, and reading and writing. The iADL-items score ranges from 0 to 59 with lower scores indicating greater impairment.	Baseline up to Week 80
Change from Baseline in ADAS-Cog13 Score	ADAS-Cog is a rater-administered instrument, designed to assess the severity of dysfunction in cognition, characteristic of persons with AD. The ADAS-Cog13, the cognitive subscale of the ADAS, consists of 13 items assessing cognitive function areas most typically impaired in AD: orientation, verbal memory, language, praxis, delayed free recall, and digit cancellation. The scores range from 0 to 85, with higher scores indicating a greater deficit of global cognition.	Baseline up to Week 80
Change from Baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB)	The CDR is obtained through semi-structured interviews of individuals with AD and informants. The ratings are obtained in six domains: memory, orientation, judgment & problem-solving, community affairs, home & hobbies, and personal care. Each domain is rated on a five-point scale of functioning as follows: 0 = no impairment; 0.5 = questionable impairment; 1 = mild impairment; 2 = moderate impairment; and 3 = severe impairment. CDR-SB score is obtained by summing each of the domain scores, with scores ranging from 0 to 18. Higher scores reflect greater cognitive and functional impairment.	Baseline up to Week 80
Change from Baseline in Mini-Mental State Examination (MMSE)	MMSE is a standard staging and assessment tool in AD, designed for grading the cognitive state of individuals with AD. The scale comprises tasks concerning orientation, memory, attention, language, and praxis to evaluate an individual's cognitive state. MMSE total score ranges from 0 to 30, with lower scores indicative of greater cognitive impairment.	Baseline up to Week 80
Change from Baseline in Quality of Life in Alzheimer's Disease (QoL-AD)	The QOL-AD tool is a 13-item assessment with each question scored on a 4-point scale where 1 = poor quality of life and 4 = excellent quality of life. Scores range from 13 to 52 with higher scores indicating better quality of life.	Baseline up to Week 80
Change from Baseline in Neuropsychiatric Inventory Questionnaire (NPI-Q) Score	NPI-Q is a validated questionnaire completed by informants about participants for whom they care. Each of the 12 NPI-Q domains contains a survey question (answered in Yes/No) that reflects the cardinal symptoms of that domain. If the domain response is "Yes," the informant then rates the severity of the symptoms present within the last month on a 3-point scale and the distress of the symptom using a 5-point scale. The total NPI-Q severity score is the sum of the individual severity scores for each symptom and ranges from 0 to 36, with higher scores indicating more severe behavioral impairment. The total NPI-Q distress score is the sum of the individual distress scores for each symptom and ranges from 0 to 60, with higher scores indicating greater caregiver distress.	Baseline up to Week 80
Change from Baseline in EuroQoL 5-Dimension 5-Level (EQ-5D-5L)	EQ-5D-5L is a self-report survey that measures quality of life. The EQ-5D-5L consists of an EQ-5D descriptive system and EQ visual analog scale (EQ VAS). The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has five levels, each assigned a unique 1-digit number: no problems, slight problems, moderate problems, severe problems, and extreme problems. The digits are combined into a 5-digit number that describes the participant's health state. The EQ VAS records the participant's health on a vertical visual analog scale, where the endpoints are labeled 0= the best health you can imagine, and 100= the worst health you can imagine.	Baseline up to Week 80
Change from Baseline in Resource Utilization in Dementia (RUD)	The RUD questionnaire is a standardized tool and the most widely used instrument for resource use data collection in dementia, enabling comparison of costs of care across countries with differing health care provisions. It is designed to collect data on formal and informal care resource use and to be useful in different care settings, across different countries and care systems, and in both clinical studies and observational cost-of-illness studies.	Baseline up to Week 80
Change from Baseline in Zarit Burden Interview (ZBI)	ZBI consists of 22 items. Twenty-one of the items are designed to measure several aspects of burden, whereas Item 22 is a global measure of burden. Response options for each item range from 0-4, and total scores range from 0-88, with higher scores indicating greater self-reported burden.	Baseline up to Week 80
Percentage of Participants with No Clinical Progression at One Year	No clinical progression in participants will be defined as no decline in CDR-SB score. The CDR is obtained through semi-structured interviews of individuals with AD and informants. The ratings are obtained in six domains: memory, orientation, judgment & problem-solving, community affairs, home & hobbies, and personal care. Each domain is rated on a five-point scale of functioning as follows: 0 = no impairment; 0.5 = questionable impairment; 1 = mild impairment; 2 = moderate impairment; and 3 = severe impairment. CDR-SB score is obtained by summing each of the domain scores, with scores ranging from 0 to 18. Higher scores reflect greater cognitive and functional impairment.	Baseline up to Week 80
Number of Participants with Treatment-Related Adverse Events (TEAEs)		Baseline up to Week 80
Number of Participants with Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI)		Baseline up to Week 80
Number of Participants who Discontinue or Withdraw due to TEAE		Baseline up to Week 80
Number of Participants with Anti-Drug Antibodies (ADA) and Neutralizing Antibodies		Baseline up to Week 80
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)		Baseline up to Week 80
Number of Participants with Suicidal Ideation and Behavior as Measured by Columbia-Suicide Severity Rating Scale (C-SSRS)	The C-SSRS includes 'yes' or 'no' responses for assessment of suicidal ideation and behavior as well as numeric ratings for severity of ideation, if present (from 1 to 5, with 5 being the most severe). Greater lethality or potential lethality of suicidal behaviors (endorsed on the behavior subscale) indicates increased risk.	Baseline up to Week 80
CSF Concentrations of ACU193 in a Subset of Participants		Up to Week 76
Change From Baseline in Amyloid Plaque Load or Deposition Measured by Positron Emission Tomography (PET) in Centiloids		Baseline up to Week 76
Change from Baseline in Volumetric Magnetic Resonance Imaging (vMRI) of Whole Brain Volume, Ventricular Volume, and Volume of Selected Regions of Interest		Baseline up to Week 76
Change from Baseline in CSF Concentrations of Amyloid, Tau and Other Neurodegenerative Biomarkers		Baseline up to Week 76
Change from Baseline in CSF Concentrations of Amyloid, Tau, and Other Neurodegenerative Biomarkers in a Subset of Participants		Baseline up to Week 76
Change from Baseline in Blood Concentrations of Amyloid, Tau, and Other Neurodegenerative Biomarkers		Baseline up to Week 76
Correlation Between Change in Biomarker that Reflect Disease Progression and Clinical Changes	Assessment of the correlation between change in clinical outcomes (iADRS, CDR-SB, ADCS-iADL, ADAS-Cog13, and MMSE) and change in biomarker (amyloid PET) will be determined by computing Pearson's correlation coefficient for each treatment group.	Up to 80 weeks
Effect of sabirnetug on Clinical Progression as Compared to Placebo Assessed Using Time Saved Analysis as Measured by iADRS		Baseline up to Week 80
Effect of sabirnetug on Clinical Progression as Compared to Placebo Assessed Using Time Saved Analysis as Measured by ADCS-iADL		Baseline up to Week 80
Effect of sabirnetug on Clinical Progression as Compared to Placebo Assessed Using Time Saved Analysis as Measured by ADAS-Cog13		Baseline up to Week 80
Effect of sabirnetug on Clinical Progression as Compared to Placebo Assessed Using Time Saved Analysis as Measured by CDR-SB		Baseline up to Week 80
Effect of sabirnetug on Clinical Progression as Compared to Placebo Assessed Using Time Saved Analysis as Measured by MMSE		Baseline up to Week 80
Serum Concentration of sabirnetug		Pre-dose and multiple timepoints post dose up to 80 weeks
Concentration of sabirnetug in Cerebrospinal Fluid (CSF)		Up to Week 76
Correlation Between sabirnetug Exposure with Clinical Efficacy Measures	Correlation between sabirnetug exposure and clinical outcomes (including iADRS, CDR-SB, ADCS-iADL, ADAS-Cog13, and MMSE) will be assessed in this study.	Baseline up to 80 weeks
Target Engagement Assessed by Measurement of sabirnetug- Amyloid-β oligomer (AβO) Complex in CSF		Up to Week 76

Collaborators and Investigators

• Sponsor: Acumen Pharmaceuticals
• Investigators: Study Director: Eric Siemers, MD, Acumen Pharmaceuticals

Publications and helpful links

General Publications

• Siemers E, Feaster T, Sethuraman G, Sundell K, Skljarevski V, Cline EN, Zhang H, Jerecic J, Honig LS, Salloway S, Sperling R, Trame MN, Dodds MG, Johnson K. INTERCEPT-AD, a phase 1 study of intravenous sabirnetug in participants with mild cognitive impairment or mild dementia due to Alzheimer's disease. J Prev Alzheimers Dis. 2025 Jan;12(1):100005. doi: 10.1016/j.tjpad.2024.100005. Epub 2025 Jan 1.

Study record dates

Study Major Dates

• Study Start (Actual): February 29, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: March 13, 2024
• First Submitted That Met QC Criteria: March 21, 2024
• First Posted (Actual): March 28, 2024

Study Record Updates

• Last Update Posted (Estimated): October 27, 2025
• Last Update Submitted That Met QC Criteria: October 23, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Mild Cognitive Impairment; MCI; Memory Loss; Mild Alzheimer's Disease; Memory Problems
• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurobehavioral Manifestations; Neurocognitive Disorders; Cognition Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Cognitive Dysfunction; Alzheimer Disease; Memory Disorders
• Other Study ID Numbers: ACU193-201; 2023-509807-34-00 (Registry Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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