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

A Phase 1b, Randomized, Double-blind, Placebo-controlled Pilot Study to Evaluate the Effects of NMRA-323511 Among Healthy Elderly and Adults With Agitation Associated With Dementia Due to Alzheimer's Disease

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 Overview

• Status: Completed
• Conditions: Healthy Elderly; Alzheimer's Disease
• Intervention / Treatment: Drug: Placebo; Drug: NMRA-323511

• Study Type: Interventional
• Enrollment (Actual): 87
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Chandler, Arizona, United States, 85286
      • Neumora Investigator Site
    • Tempe, Arizona, United States, 85283
      • Neumora Investigator Site
  • California
    • Costa Mesa, California, United States, 92626
      • Neumora Investigator Site
    • Lomita, California, United States, 90717
      • Neumora Investigator Site
    • Walnut Creek, California, United States, 94596
      • Neumora Investigator Site
  • Florida
    • Bradenton, Florida, United States, 34205
      • Neumora Investigator Site
    • Greenacres City, Florida, United States, 33467
      • Neumora Investigator Site
    • Hallandale, Florida, United States, 33009
      • Neumora Investigator Site
    • Hialeah, Florida, United States, 33016
      • Neumora Investigator Site
    • Miami, Florida, United States, 33126
      • Neumora Investigator Site
    • Miami, Florida, United States, 33137
      • Neumora Investigator Site
    • Miami, Florida, United States, 33155
      • Neumora Investigator Site
    • Miami Springs, Florida, United States, 33166
      • Neumora Investigator Site
    • Orlando, Florida, United States, 32807
      • Neumora Investigator Site
    • Pembroke Pines, Florida, United States, 33024
      • Neumora Investigator Site
    • Port Orange, Florida, United States, 32127
      • Neumora Investigator Site
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Neumora Investigator Site
  • Hawaii
    • Honolulu, Hawaii, United States, 96817
      • Neumora Investigator Site
  • Idaho
    • Boise, Idaho, United States, 83704
      • Neumora Investigator Site
  • Massachusetts
    • Belmont, Massachusetts, United States, 02478
      • Neumora Investigator Site
  • Michigan
    • Troy, Michigan, United States, 48085
      • Neumora Investigator Site
  • New Jersey
    • Toms River, New Jersey, United States, 08755
      • Neumora Investigator Site
  • New York
    • Brooklyn, New York, United States, 11229
      • Neumora Investigator Site
    • East Syracuse, New York, United States, 13057
      • Neumora Investigator Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Neumora Investigator Site
  • Texas
    • Mesquite, Texas, United States, 75149
      • Neumora Investigator Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Part A: Placebo	Drug: Placebo; Participants will receive matching placebo tablets orally.
Placebo Comparator: Part B: Placebo	Drug: Placebo; Participants will receive matching placebo tablets orally.
Experimental: Part A: NMRA-323511	Drug: NMRA-323511; Participants will receive NMRA-323511 orally.
Experimental: Part B: NMRA-323511	Drug: NMRA-323511; Participants will receive NMRA-323511 orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	Baseline to Week 8

Collaborators and Investigators

• Sponsor: Neumora Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 9, 2024
• Primary Completion (Actual): November 19, 2025
• Study Completion (Actual): November 19, 2025

Study Registration Dates

• First Submitted: August 6, 2024
• First Submitted That Met QC Criteria: August 6, 2024
• First Posted (Actual): August 9, 2024

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Alzheimer's Disease; Agitation Associated Dementia; NMRA-323511
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: NMRA-323511-104

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No