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

NCT06335173 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: ACU193-2012023-509807-34-00
• Study Type: interventional
• Target: 542
• Locations: 5 countries
• Sites: 68

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.

Conditions

Alzheimer Disease

Keywords

Mild Cognitive Impairment; MCI; Mild Alzheimer's Disease; Memory Loss; Memory Problems

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (32)

• Change from Baseline in ADCS-iADL Score

  Baseline up to Week 80

• Change from Baseline in ADAS-Cog13 Score

  Baseline up to Week 80

• Change from Baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB)

  Baseline up to Week 80

• Change from Baseline in Mini-Mental State Examination (MMSE)

  Baseline up to Week 80

• Change from Baseline in Quality of Life in Alzheimer's Disease (QoL-AD)

  Baseline up to Week 80

Study Arms (4)

Double-blind Treatment (DBT) Period: sabirnetug 35 mg/kg

EXPERIMENTAL

Participants will receive sabirnetug, 35 milligrams per kilogram (mg/kg), Q4W as intravenous (IV) infusion during the DBT period.

Drug: sabirnetug

DBT Period: sabirnetug 50 mg/kg

EXPERIMENTAL

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

DBT Period: Placebo

PLACEBO COMPARATOR

Participants will receive sabirnetug matching placebo, Q4W as an IV infusion during the DBT period.

Drug: Placebo

Open-Label Extension (OLE) Period: sabirnetug 35 mg/kg

EXPERIMENTAL

Participants will receive sabirnetug, 35 mg/kg, Q4W as an IV infusion during the OLE period.

Drug: sabirnetug

Interventions

sabirnetug DRUG

Intravenous sabirnetug

DBT Period: sabirnetug 50 mg/kg; Double-blind Treatment (DBT) Period: sabirnetug 35 mg/kg; Open-Label Extension (OLE) Period: sabirnetug 35 mg/kg

Placebo DRUG

Intravenous Placebo

DBT Period: Placebo

Eligibility Criteria

• Age: 50 Years - 90 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• National Institute on Aging-Alzheimer's Association (NIA-AA) criteria for mild cognitive impairment (MCI) due to Alzheimer's Disease (AD) or probable AD
• Screening score between 22 and 30 (inclusive) on the Mini-Mental State Examination (MMSE)
• 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
• 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

You may not qualify if:

• 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:
• Any suicide attempt or preparatory acts/behavior on the C-SSRS Baseline/Screening in the last six months
• Suicidal ideation in the last six months as defined by a positive response to Question 5 (Suicidal Ideation) on the C-SSRS Baseline/Screening
• 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

Sponsors & Collaborators

• Acumen Pharmaceuticals: lead

Study Sites (68)

The Neurology Center of Southern California - Carlsbad

Carlsbad, California, 92011-4219, United States

Location

Neurology Center of North Orange County

Fullerton, California, 92835, United States

Location

Irvine Medical Research

Irvine, California, 92614, United States

Location

Healthy Brain Research

Long Beach, California, 90804, United States

Location

Syrentis Clinical Research

Santa Ana, California, 92705, United States

Location

CenExel - California Neuroscience Research Medical Group, Inc (CNR)

Sherman Oaks, California, 91403-2131, United States

Location

Research Center for Clinical Studies, LLC

Norwalk, Connecticut, 06851-4903, United States

Location

Re:Cognition Health - Fairfax

Washington D.C., District of Columbia, 22031, United States

Location

JEM Research Institute

Atlantis, Florida, 33462, United States

Location

Bradenton Research Center

Bradenton, Florida, 34205, United States

Location

Gil Fernandez-Yera, MD, PA

Coral Gables, Florida, 33135, United States

Location

Brain Matters Research

Delray Beach, Florida, 33445, United States

Location

Coral Clinical Research

Homestead, Florida, 33032, United States

Location

K2 Medical Research - Villages

Lady Lake, Florida, 32159, United States

Location

Finlay Medical Research

Miami, Florida, 33126, United States

Location

Aqualane Clinical Research

Naples, Florida, 34105-8522, United States

Location

Ocala Health - Family Care Specialists - Ocala I

Ocala, Florida, 34470, United States

Location

Progressive Medical Research

Port Orange, Florida, 32127, United States

Location

Alzheimer's Research and Treatment Center - Stuart

Stuart, Florida, 34997, United States

Location

K2 Medical Research - Tampa

Tampa, Florida, 33607, United States

Location

Charter Research - Lady Lake

The Villages, Florida, 32162, United States

Location

Alzheimers Research and Treatment Center - Wellington

Wellington, Florida, 33414, United States

Location

Conquest Research

Winter Park, Florida, 32789, United States

Location

Charter Research - Winter Park

Winter Park, Florida, 32792, United States

Location

Columbus Memory Center

Columbus, Georgia, 31909, United States

Location

CenExel - iResearch Atlanta

Decatur, Georgia, 30030, United States

Location

Office of Jeffrey S. Ross, MD

Northbrook, Illinois, 60640, United States

Location

Boston Center for Memory

Newton, Massachusetts, 02459, United States

Location

Hattiesburg Clinic - Memory Center

Hattiesburg, Mississippi, 39401-7246, United States

Location

ActivMed Practices and Research

Portsmouth, New Hampshire, 03801, United States

Location

The Cognitive and Research Center of New Jersey

Springfield, New Jersey, 07081, United States

Location

CenExel - Advanced Memory Research Institute of NJ

Toms River, New Jersey, 08755, United States

Location

Neurological Associates of Albany

Albany, New York, 12208, United States

Location

AMC Research

Matthews, North Carolina, 28105, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Summit Research Network

Portland, Oregon, 97210, United States

Location

Abington Neurological Associates

Abington, Pennsylvania, 19001, United States

Location

Keystone Clinical Research

Norristown, Pennsylvania, 19462, United States

Location

Rhode Island Mood and Memory

East Providence, Rhode Island, 02914, United States

Location

Neurology Clinic. P.C

Cordova, Tennessee, 38018, United States

Location

The Alliance for Multispecialty Research LLC (AMR)

Knoxville, Tennessee, 37920-1511, United States

Location

Senior Adult Specialty Research

Austin, Texas, 78757, United States

Location

Gadolin Research, LLC

Beaumont, Texas, 77702, United States

Location

Kerwin Medical Center

Dallas, Texas, 75231, United States

Location

Okanagan Clinical Trials

Kelowna, British Columbia, Canada

Location

Hippocampe d/b/a Ottawa Memory Clinic

Ottawa, Ontario, Canada

Location

Toronto Memory Program (TMP) (Neurology Research Inc.)

Toronto, Ontario, Canada

Location

MoCA Research and Innovations

Greenfield Park, Quebec, Canada

Location

Charité - Universitaetsmedizin Berlin

Berlin, Germany

Location

University Hospital of Cologne

Cologne, Germany

Location

Zentralinstitut für seelische Gesundheit

Mannheim, Germany

Location

Technical University of Munich, School of Medicine and Health, Klinikum rechts der Isar

Munich, Germany

Location

Hospital Universitari General de catalunya

Sant Cugat del Vallès, Barcelona, Spain

Location

Fundacion Neuropolis - Hospital Viamed Montecanal

Cuarte de Huerva, Zaragoza, Spain

Location

Fundacio ACE

Barcelona, Spain

Location

Policlínica Gipuzkoa

Donostia / San Sebastian, Spain

Location

Cae Oroitu

Getxo, Spain

Location

Hospital Ruber

Madrid, Spain

Location

Hospital Victoria Eugenia

Seville, Spain

Location

Hospital Universitari i Politècnic La Fe

Valencia, Spain

Location

Re:Cognition Health - London

London, Greater London, United Kingdom

Location

St. Pancras Clinical Research Ltd.

London, Greater London, United Kingdom

Location

Re:Cognition Health - Winchester

Winchester, Hampshire, United Kingdom

Location

Neuroclin Glasgow

Motherwell, Lanarkshire, United Kingdom

Location

Panthera Bio-Partners - Preston

Preston, Lancashire, United Kingdom

Location

Re:Cognition Health - Guildford

Guildford, Surrey, United Kingdom

Location

Panthera Biopartners - Sheffield

Sheffield, Yorkshire, United Kingdom

Location

Re:Cognition Health - Bristol

Bristol, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 39800458 DERIVED

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction; Memory Disorders

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2024
• First Posted: March 28, 2024
• Study Start: February 29, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: October 27, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (4); ES (8); US (44); DE (4); GB (8)