A Study to Evaluate Efficacy and Safety of Intravenous ACU193 in Participants With Early Alzheimer's Disease (ALTITUDE-AD)

Acumen Pharmaceuticals

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Alzheimer Disease

Treatments: Drug: ACU193; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT06335173

2023-509807-34-00 (Registry Identifier)

ACU193-201

Details and patient eligibility

About

The primary purpose of this study is to evaluate the efficacy of ACU193 infusions administered once every four weeks (Q4W) in slowing cognitive and functional decline as compared to placebo in participants with early Alzheimer's disease.

Enrollment: 2,040 estimated patients

Sex: All

Ages: 50 to 90 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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2,040 participants in 4 patient groups, including a placebo group

Double-blind Treatment (DBT) Period: ACU193 35 mg/kg

Experimental group

Description:

Participants will receive ACU193, 35 milligrams per kilogram (mg/kg), Q4W as intravenous (IV) infusion during the DBT period.

Treatment:

Drug: ACU193

DBT Period: ACU193 50 mg/kg

Experimental group

Description:

Participants will receive ACU193, 35 mg/kg, for the first two doses, followed by AUC193, 50 mg/kg, Q4W as an IV infusion during the DBT period.

Treatment:

Drug: ACU193

DBT Period: Placebo

Placebo Comparator group

Description:

Participants will receive AUC193 matching placebo, Q4W as an IV infusion during the DBT period.

Treatment:

Drug: Placebo

Open-Label Extension (OLE) Period: ACU193 35 mg/kg

Experimental group

Description:

Participants will receive ACU193, 35 mg/kg, Q4W as an IV infusion during the OLE period.

Treatment:

Drug: ACU193