SABIRNETUG for Alzheimer's disease | Mild cognitive impairment due to Alzheimer's disease

Stratification factors

• Geographical region

Inclusion criteria

• {"criterion_text":"- 1. Age 50 to 90 years (inclusive) at the time of signing the Informed Consent Form (ICF).\n- 4. Consent to APOE4 genotype status assessment.\n- 5. Meet all the following criteria: a. NIA-AA criteria for MCI or mild dementia due to AD. b. Screening and Baseline score between 22 and 30 (inclusive) on the Mini-Mental State Examination (MMSE). c. Screening and Baseline score of 0.5 or 1.0 on the CDR-GS and Screening and Baseline score ≥0.5 on the CDR Memory Box score. d. Evidence of cerebral amyloid accumulation by either PET scan or CSF. (CSF should not be collected from participants on anticoagulation treatment.) Participants will have only one assessment to determine evidence of cerebral amyloid accumulation – CSF or amyloid PET.\n- 12. OLE: Participants who complete treatment in the double-blind treatment period will be eligible for the OLE after signing consent.\n- 6. 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 (Week 0) and every attempt should be made to keep them at stable doses throughout the study.\n- 7. If on anticoagulants, must have their anticoagulation status optimized and stable for at least one month (four weeks) before Screening, and are not permitted to participate in CSF assessments due to bleeding risk.\n- 8. Have a reliable informant or study partner who is willing and able to perform the roles specified in the study partner ICF, including providing support and accompanying the participant to study visits or be available by telephone at designated times.\n- 9. Individuals with prior childbearing potential who are: a. Infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation) or b. Post-menopausal – defined as 12 months with no menses without an alternative medical cause.\n- 10. Sperm-producing individuals in a sexual relationship with individuals of childbearing potential must use adequate contraception (e.g., condom) and must not donate sperm during the study and for 180 days after the last dose of the study drug.\n- 11. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.\n- 2. Able to give written informed consent.\n- 3. Body weight of at least 30 kg (66 lbs) and no more than 160 kg (352 lbs) at Screening"}

Exclusion criteria

• {"criterion_text":"- 1. Contraindications for magnetic resonance imaging (MRI) studies, including claustrophobia, the presence of metal (ferromagnetic) implants, or a cardiac pacemaker and/or defibrillator that is not compatible with MRI.\n- 18. Known hypersensitivity to any component of sabirnetug, including excipients.\n- 19. A result below the cut-off value in an amyloid screening blood test at Screening 1. This test is being used as an enrichment strategy. In all regions except the EU (European Union) and UK (United Kingdom), this test is a mandatory part of the screening process. Exceptions apply for participants with prior PET or CSF evidence of amyloid positivity; these cases should be discussed with a medical monitor to determine if they can proceed to Screening 2 without the amyloid screening blood test.\n- 10. Ongoing or new clinically significant laboratory abnormality, as determined by the site investigator.\n- 11. Within one year before Screening, any of the following: myocardial infarction; moderate or severe congestive heart failure, New York Heart Association class III or IV; hospitalization for, or symptom of, unstable angina; syncope due to orthostatic hypotension or unexplained syncope; known significant structural heart disease (e.g., significant valvular disease, hypertrophic cardiomyopathy), hospitalization for arrhythmia, uncontrolled hypertension or clinically significant abnormalities in ECG, or history or presence of clinically significant QTc interval prolongation or family history of long QTc.\n- 2. MRI of brain that is inconsistent with MCI or AD or results showing greater than four amyloid-related imaging abnormalities hemorrhage/hemosiderin deposition (ARIA-H), presence of any amyloid-related imaging abnormalities edema/effusions (ARIA-E), or superficial siderosis.\n- 3. 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, or any other neurological condition that may be contributing to cognitive impairment beyond that caused by the participant’s AD in the judgement of the investigator.\n- 4. Received any investigational product within six months (24 weeks) prior to Baseline (Week 0).\n- 5. Received any monoclonal antibody within six months (24 weeks) prior to Baseline (Week 0) that reduces amyloid plaques or tau load in the brain, including sabirnetug\n- 6. Known allergy to biological products.\n- 7. Immunologic disease requiring treatment with plasmapheresis. If a participant is on immunosuppressive drugs, the investigator should discuss the case with the medical monitor.\n- 8. Modified Hachinski Ischemic Scale score >4.\n- 20. OLE:They were discontinued from study treatment during the double-blind treatment period.\n- 21. OLE:Their participation in the OLE is deemed inappropriate by the investigator (e.g., any serious medical condition or concerns that preclude the participant’s safe participation in the OLE or ability to comply with the required procedures.\n- 22. OLE:They have unresolved ARIA findings at the end of the double-blind treatment period scan that have required suspension or discontinuation of dosing (see Section 7.1.1).\n- 9. 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, including psychiatric, hepatic, renal, gastroenterological, respiratory, cardiovascular, endocrinological, immunologic, or hematologic disorders\n- 12. 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).\n- 13. 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.\n- 14. Suicide risk, as determined by meeting any of the following criteria: a.\tAny suicide attempt or preparatory acts/behavior on the Columbia-Suicide Severity Rating Scale (C-SSRS) Baseline/Screening in the last six months. b.\tSuicidal ideation in the last six months as defined by a positive response to Question 5 (Suicidal Ideation) on the C-SSRS Baseline/Screening. c.\tSignificant risk of suicide, as judged by the site investigator.\n- 15. Alcohol use disorder and/or substance use disorder within the last five years.\n- 16. Conditions that may affect cognitive assessments during the study (e.g., planned surgery requiring general anesthesia).\n- 17. Known genetic mutation that causes autosomal dominant AD."}

Primary endpoints

• {"endpoint_text":"- Change from Baseline to Week 80 in the iADRS score.","definition_or_measurement_approach":"Change from Baseline to Week 80 in the Integrated Alzheimer’s Disease Rating Scale (iADRS) score; primary objective compares sabirnetug Q4W infusions vs placebo based on change from Baseline to Week 80 in iADRS."}

Secondary endpoints

• {"endpoint_text":"- 1. Change from Baseline to Week 80 in the ADCS-iADL, ADAS-Cog13, CDR-SB, and MMSE.","definition_or_measurement_approach":"Change from Baseline to Week 80 in listed cognitive and functional scale scores (ADCS-iADL, ADAS-Cog13, CDR-SB, MMSE)."}
• {"endpoint_text":"- 2. Change from Baseline to Week 80 in QoL-AD","definition_or_measurement_approach":"Change from Baseline to Week 80 in the QoL-AD (Quality of Life in Alzheimer's Disease) score."}
• {"endpoint_text":"- 3. Further Secondary, Clinical, Safety, Pharmacodynamic, Pharmacokinetics, Pharmacogenomic, Blood and CSF Biomarker and Exploratory Endpoints are visible in the study protocol.","definition_or_measurement_approach":"See study protocol for detailed definitions; includes safety, PD, PK, pharmacogenomic, blood and CSF biomarker and exploratory endpoints."}
• {"endpoint_text":"- 4. OLE: Changes from Baseline to Week 104 and Week 132 for iADRS, CDR-SB, ADCS-iADL, ADAS-Cog13, and MMSE as measured by delayed-start analysis.","definition_or_measurement_approach":"OLE (open-label extension) outcomes: changes from Baseline to Week 104 and Week 132 for listed scales assessed by delayed-start analysis."}

Other endpoints

• {"endpoint_text":"- Further Secondary, Clinical, Safety, Pharmacodynamic, Pharmacokinetics, Pharmacogenomic, Blood and CSF Biomarker and Exploratory Endpoints are visible in the study protocol.","definition_or_measurement_approach":"Detailed exploratory and biomarker endpoint definitions are provided in the study protocol (includes blood and CSF biomarkers, imaging, PK/PD, pharmacogenomics and other exploratory assessments)."}

Methods

• Posters (print) — recruitment posters listed in recruitment materials (target: patients/caregivers), available in Spanish versions.
• Social media advertisements — social media ad materials (target: patients/caregivers/general public), Spanish versions provided.
• Print adverts — print ads / tearpads for patient recruitment (target: patients/caregivers), Spanish versions.
• Study website — multilingual study website (annotated and translations) to provide study information and contact details; screenshots provided in materials.
• Patient brochure — study brochure for potential participants (Spanish version available).
• Tearpad / tear-off materials — printed recruitment material for distribution in clinics.
• Study website translations and localized materials (e.g., Spanish translations) to support country-specific recruitment.

France

Earliest CTIS Part Ii Submission Date

28-05-2024

Latest Decision Or Authorization Date

22-07-2024

Processing Time Days

55

Number Of Sites

11

Number Of Participants

90

Spain

Earliest CTIS Part Ii Submission Date

14-06-2024

Latest Decision Or Authorization Date

21-01-2026

Processing Time Days

586

Number Of Sites

8

Number Of Participants

50

Germany

Earliest CTIS Part Ii Submission Date

14-05-2024

Latest Decision Or Authorization Date

20-01-2026

Processing Time Days

616

Number Of Sites

4

Number Of Participants

35

Primary sponsor

Full Name

Acumen Pharmaceuticals Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Worldwide Clinical Trials d.o.o.

Responsibilities

Project management and broad CRO responsibilities including TMF, monitoring and multiple operational tasks (sponsorDuties codes: [1,2,5,6,8,9,10,11,12,13,15 (TMF)])

Name

Signant Health Global LLC

Responsibilities

Rater / Scale Management

Name

Suvoda LLC

Responsibilities

Clinical operations / eClinical service (sponsorDuties code 3)

Name

Sitero LLC

Responsibilities

Clinical Trial Management System

Name

Bioclinica Inc.

Responsibilities

MRI & PET Analysis

Name

eResearchTechnology GmbH

Responsibilities

Cardiac Safety

Name

Iqvia Laboratories Limited

Responsibilities

Laboratory services (sponsorDuties code 4)

Third parties

• {"country":"Germany","full_name":"Catalent Germany Schorndorf GmbH","duties_or_roles":"sponsorDuties codes: [14]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Meso Scale Diagnostics LLC","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Ledger Run Inc.","duties_or_roles":"Investigator payment system (sponsorDuties code 15)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Signant Health Global LLC","duties_or_roles":"Rater / Scale Management (sponsorDuties code 15)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"sponsorDuties codes: [3]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Merative US LP","duties_or_roles":"sponsorDuties codes: [7]","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Bioagilytix Labs LLC","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Voute","duties_or_roles":"Participant Reimbursement (sponsorDuties code 15)","organisation_type":"Pharmaceutical company"}
• {"country":"Croatia","full_name":"Worldwide Clinical Trials d.o.o.","duties_or_roles":"Multiple sponsor duties including project management, monitoring, TMF and operational tasks (sponsorDuties codes: [1,10,11,12,13,15 (TMF),2,5,6,8,9])","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"eResearchTechnology GmbH","duties_or_roles":"Cardiac Safety (sponsorDuties code 15)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Sitero LLC","duties_or_roles":"Clinical Trial Management System (sponsorDuties code 15)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"MRI & PET Analysis (sponsorDuties code 15)","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Oracle America Inc.","duties_or_roles":"sponsorDuties codes: [8]","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Iqvia Laboratories Limited","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Non-Pharmaceutical company"}