ACU193 for Early Alzheimer's Disease

(ALTITUDE-AD Trial)

Recruiting at 128 trial locations

Overseen By Alyssa Carroll

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Acumen Pharmaceuticals

Must be taking: Cholinesterase inhibitors, Memantine

Disqualifiers: Neurological disease, Malignant disease, Depression, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 20

540 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are using cholinesterase inhibitors or memantine for Alzheimer's symptoms, you must keep the doses stable for at least three months before starting the trial and try to maintain them throughout the study.

What data supports the effectiveness of the drug ACU193 for early Alzheimer's disease?

ACU193 is the first treatment designed to specifically target amyloid β oligomers, which are believed to be directly responsible for memory and cognitive decline in Alzheimer's disease. This approach is based on the hypothesis that blocking these oligomers could stop or reverse cognitive decline, a strategy not yet tested in previous trials. ^{1 2 3 4 5}

Is ACU193 safe for humans?

ACU193 is a new treatment being tested for Alzheimer's disease, and while specific safety data for ACU193 isn't available, similar treatments like aducanumab have shown some safety concerns, such as amyloid-related imaging abnormalities (changes seen in brain scans). It's important to discuss potential risks with the trial team. ^{2 6 7 8 9}

How is the drug ACU193 different from other Alzheimer's treatments?

ACU193 is unique because it is a monoclonal antibody that specifically targets soluble amyloid β oligomers, which are believed to be the most toxic form of amyloid β contributing to Alzheimer's disease. Unlike other treatments that target amyloid plaques or monomers, ACU193 is the first to focus on these oligomers, aiming to stop or reverse cognitive decline associated with Alzheimer's. ^{2 8 9 10 11}

Research Team

Eric Siemers, MD

Principal Investigator

Acumen Pharmaceuticals

Eric Siemers, MD

Principal Investigator

Acumen Pharmaceuticals

Eligibility Criteria

This trial is for individuals with early Alzheimer's Disease who can attend regular infusions every four weeks. Specific eligibility details are not provided, but typically participants must meet certain health criteria and agree to follow the study procedures.

Inclusion Criteria

My weight is between 66 and 352 lbs.

I agree to have my APOE4 gene status checked.

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 and baseline 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

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: 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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-blind Treatment (DBT) Period

Participants receive either sabirnetug or placebo as an intravenous infusion every four weeks

80 weeks

20 visits (in-person, every 4 weeks)

Open-Label Extension (OLE) Period

Participants receive sabirnetug as an intravenous infusion every four weeks

Long-term

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• ACU193

Trial Overview The trial is testing ACU193, a drug given through an IV once a month, to see if it slows down memory loss and daily functioning decline in people with early Alzheimer's compared to a placebo (a treatment with no active drug).

Participant Groups

Group I: Open-Label Extension (OLE) Period: sabirnetug 35 mg/kg Experimental Treatment 1 Intervention

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

Group II: Double-blind Treatment (DBT) Period: sabirnetug 35 mg/kg Experimental Treatment 1 Intervention

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

Group III: DBT Period: sabirnetug 50 mg/kg Experimental Treatment 1 Intervention

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.

Group IV: DBT Period: Placebo Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

Acumen Pharmaceuticals

Lead Sponsor

Trials

3

Recruited

630+

Findings from Research

The study identified that using the Functional Activities Questionnaire and the Clinical Dementia Rating Sum of Boxes as endpoints can detect significant changes in Alzheimer's disease progression, particularly in patients with Late Mild Cognitive Impairment, suggesting these measures are effective for future trials.

Composite measures showed even greater sensitivity, indicating that using a combination of endpoints could enhance the success rate of Alzheimer's clinical trials by better capturing the disease's progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The importance of endpoint selection: How effective does a drug need to be for success in a clinical trial of a possible Alzheimer's disease treatment? Evans, S., McRae-McKee, K., Wong, MM., et al.[2019]

Alzheimer's disease (AD) is linked to elevated levels of amyloid β (Aβ) peptide, particularly soluble Aβ oligomers (AβOs), which are believed to cause memory and cognitive decline; however, traditional therapies targeting Aβ have largely failed in clinical trials.

ACU193 is the first immunotherapeutic specifically designed to target AβOs and is currently undergoing human clinical trials, representing a new approach to potentially halt or reverse cognitive decline in AD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ACU193: An Immunotherapeutic Poised to Test the Amyloid β Oligomer Hypothesis of Alzheimer's Disease. Krafft, GA., Jerecic, J., Siemers, E., et al.[2022]

Deep brain stimulation targeting the fornix (DBS-f) was found to be safe and well tolerated in a study of 42 participants with mild probable Alzheimer's disease over 12 months.

Younger participants (<65 years) showed a significant decline in cognitive function compared to older participants (≥65 years), suggesting that age may influence treatment outcomes and highlighting the need for careful subject selection in Alzheimer's clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Age on Clinical Trial Outcome in Participants with Probable Alzheimer's Disease. Targum, SD., Fosdick, L., Drake, KE., et al.[2021]

Aducanumab is a monoclonal antibody that targets aggregated amyloid β (Aβ) in Alzheimer's disease, showing an objective reduction in Aβ levels but conflicting results regarding its clinical efficacy in improving symptoms.

The most significant safety concern associated with aducanumab treatment is the occurrence of amyloid-related imaging abnormalities, which raises questions about its overall risk-benefit profile despite its recent accelerated approval by the FDA for mild Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aducanumab for the treatment of Alzheimer's disease. Tagliapietra, M.[2022]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

The importance of endpoint selection: How effective does a drug need to be for success in a clinical trial of a possible Alzheimer's disease treatment? [2019]

2. Switzerland pubmed.ncbi.nlm.nih.gov

ACU193: An Immunotherapeutic Poised to Test the Amyloid β Oligomer Hypothesis of Alzheimer's Disease. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Effect of Age on Clinical Trial Outcome in Participants with Probable Alzheimer's Disease. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

[Cognitive rehabilitation in Alzheimer's disease patients: multidisciplinary team report]. [2022]

5. Denmark pubmed.ncbi.nlm.nih.gov

Circulating cholesterol levels, apolipoprotein E genotype and dementia severity influence the benefit of atorvastatin treatment in Alzheimer's disease: results of the Alzheimer's Disease Cholesterol-Lowering Treatment (ADCLT) trial. [2018]

6. Spain pubmed.ncbi.nlm.nih.gov

Aducanumab for the treatment of Alzheimer's disease. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Emerging drugs to reduce abnormal β-amyloid protein in Alzheimer's disease patients. [2018]

8. England pubmed.ncbi.nlm.nih.gov

The antibody aducanumab reduces Aβ plaques in Alzheimer's disease. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Amyloid-Related Imaging Abnormalities in 2 Phase 3 Studies Evaluating Aducanumab in Patients With Early Alzheimer Disease. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

ACU193, a Monoclonal Antibody that Selectively Binds Soluble Aß Oligomers: Development Rationale, Phase 1 Trial Design, and Clinical Development Plan. [2023]

11. England pubmed.ncbi.nlm.nih.gov

First-In-Human safety and long-term exposure data for AAB-003 (PF-05236812) and biomarkers after intravenous infusions of escalating doses in patients with mild to moderate Alzheimer's disease. [2018]