Study to Evaluate the Effects of NMRA-323511 Among Healthy Elderly and Adults With Agitation Associated With Dementia Due to Alzheimer's Disease

Neumora Therapeutics, Inc.96 enrolled

Overview

This study consists of 2 parts, Part A and Part B. Part A is a single center, randomized, double-blind, placebo-controlled cohort designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of NMRA-323511 among healthy elderly. Part B is a multicenter, randomized, double-blinded, placebo-controlled, parallel-group cohort to evaluate the safety, tolerability, and efficacy of NMRA-323511 among adults with Agitation Associated with Dementia due to Alzheimer's Disease. Part A consists of a Screening Period (up to 28 days), a 10-day Treatment Period, and a 10- day Follow-up clinic visit after last dose of study treatment. Part B consists of a Screening Period (up to 28 days), an 8-week Treatment Period, and a 10-day Follow-up clinic visit after last dose of study treatment.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Alzheimer's Disease Healthy Elderly

Interventions

Eligibility

Sex: ALLMin age: 55 YearsMax age: 90 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: Part A * Healthy participants * Age 65 to 80 years * Body mass index (BMI) ≥18.0 and ≤32.0 kg/m\^2 at the screening and check-in visit Part B * Participants aged 55 to 90 years * Diagnosis of probable AD or Alzheimer's clinical syndrome according to the National Institute of Aging-Alzheimer's Association criteria at least 12 months prior to screening * Agitation meets the International Psychogeriatric Association (IPA) consensus definition * Mini-Mental State Examination (MMSE) score = 5 - 24 (mild to severe dementia) at screening Exclusion Criteria: Part A * Participant is actively suicidal * Is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit * Diagnosis of epilepsy taking anticonvulsants for seizure control, history of seizures Part B * Dementia or memory impairment due to a reason other than AD * Clinically significant neurologic disorder other than AD * Have any clinically significant and uncontrolled medical condition Note: Other protocol defined inclusion/exclusion criteria may apply

Locations (26)

Neumora Investigator Site

Chandler, Arizona, United States

Neumora Investigator Site

Tempe, Arizona, United States

Neumora Investigator Site

Costa Mesa, California, United States

Neumora Investigator Site

Lomita, California, United States

Neumora Investigator Site

Walnut Creek, California, United States

Neumora Investigator Site

Bradenton, Florida, United States

Neumora Investigator Site

Greenacres City, Florida, United States

Neumora Investigator Site

Hallandale, Florida, United States

Neumora Investigator Site

Hialeah, Florida, United States

Neumora Investigator Site

Miami, Florida, United States

...and 16 more locations

Outcomes

Primary Outcomes

Part A: Safety and Tolerability Assessments Based on Treatment Emergent Adverse Events (TEAEs) and Validated Clinical Scales

An AE is any untoward medical occurrence in a participant or clinical trial participant, temporally associated with the use of trial intervention, whether or not considered related to the trial intervention. Any AE occurring following the start of treatment or occurring before treatment but increasing in severity afterward were counted as treatment-emergent AE (TEAE). Clinically significant abnormalities in Clinical Laboratory Evaluations, ECGs, Vital Signs, Physical examinations, and Columbia Suicide Severity Rating Scale (C-SSRS) scores will be reported as TEAEs.

Time frame: Up to 53 days

Part B: Safety and Tolerability Assessments Based on Treatment Emergent Adverse Events and Validated Clinical Scales

An AE is any untoward medical occurrence in a participant or clinical trial participant, temporally associated with the use of trial intervention, whether or not considered related to the trial intervention. Any AE occurring following the start of treatment or occurring before treatment but increasing in severity afterward were counted as a TEAE. Clinically significant abnormalities in Clinical Laboratory Evaluations, ECGs, Vital Signs, Physical examinations, and C-SSRS scores will be reported as TEAEs.

Time frame: Up to Week 10

Part B: Change from Baseline to Week 8 on the Cohen-Mansfield Agitation Inventory (CMAI) Total Score

The CMAI is a 29-item scale to assess the frequency of agitated behaviors. The 29 agitated behaviors are categorized into agitation factors, including aggressive behavior, physically non-aggressive behavior, and verbally agitated behavior. Each item is rated over the past 2 weeks on a 7-point scale ranging from "Never" (score of 1) to "Several times per hour" (score of 7). The CMAI total score is calculated as the sum of all 29 items and range from 29 (no agitation) to 203 (most severe agitation). A score \>45 is commonly regarded as clinically significant agitation.

Time frame: Baseline to Week 8