A study to assess the efficacy and safety of ITI-1284 in the treatment of Agitation Associated with Alzheimer's Dementia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Intra-Cellular Therapies Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Psychological Phenomena [F02]

Trial duration

17 Jul 2025 → ongoing

Decision date (initial)

2025-05-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Intra-Cellular Therapies, Inc.

External identifiers

EU CT number

2024-514680-26-00

ClinicalTrials.gov

NCT06651567

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Efficacy, Safety, Pharmacokinetic

The primary efficacy objective is to evaluate the efficacy of ITI-1284 administered once daily compared with placebo in the treatment of agitation in patients with Alzheimer’s dementia, as measured by change from baseline to end of Week 12 in Cohen-Mansfield Agitation Inventory (CMAI) total score.

Secondary objectives 3

1. The key secondary efficacy objective is to evaluate the efficacy of ITI-1284, administered once daily compared with placebo in the treatment of psychosis in patients with Alzheimer’s disease, as measured by change from baseline to end of Week 12 in Clinical Global Impression-Severity (CGI-S) score.
2. The safety objective of this study is to evaluate the safety and tolerability of ITI-1284 administered once daily compared with placebo in the treatment of psychosis in patients with AD, as assessed by adverse events (AEs), vital signs, electrocardiograms (ECGs), clinical laboratory tests, modified physical examinations, assessment of cognition by Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Columbia-Suicide Severity Rating Scale (C-SSRS) and extrapyramidal symptoms (EPS) as assessed by Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Rating Scale (BARS), and Simpson-Angus Scale (SAS).
3. The pharmacokinetic (PK) objective of this study is to evaluate the plasma concentrations of ITI-1284 and its metabolites following SL administration of ITI-1284 once daily.

Conditions and MedDRA coding

Agitation Associated with Alzheimer’s Dementia

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Applicable to all EU countries except Bulgaria and Croatia Able to provide consent before the initiation of any study-specific procedures as follows: o If patient is deemed competent to provide informed consent in the judgement of the Investigator, can understand the nature of the trial and protocol requirements, and provide signed informed consent in conjunction with an acknowledgment from the patient’s representative or surrogate (eg, caregiver, family member, friend, partner, Legally Authorized Representative [LAR]); or o If patient is deemed not competent to provide informed consent, with the patient’s assent (if capable) or lack of dissent, consent may be provided by an appropriate person (eg, patient's LAR) in accordance with local regulations; Applicable to Bulgaria only: Able to provide consent before the initiation of any study-specific procedures as follows: o If patient is deemed competent to provide informed consent in the judgment of the Investigator, can understand the nature of the trial and protocol requirements, and provide signed informed consent in conjunction with an acknowledgment from the patient’s caregiver; or o If patient is deemed not competent to provide informed consent, with the patient’s assent (if capable) or lack of dissent, consent may be provided by an appropriate person (eg, patient’s LAR) in accordance with local regulations; Applicable to Croatia only: Able to provide consent before the initiation of any study-specific procedures as follows: o Patient is deemed competent to provide informed consent in the judgment of the Investigator, can understand the nature of the trial and protocol requirements, and provide signed informed consent;
2. Male or female, ≥ 55 years of age
3. Has a body mass index (BMI) of 18–40 kg/m2 inclusive
4. Has an onset of symptoms of agitation at least 2 weeks prior to Screening (Visit 1)
5. Meets clinical criteria for Alzheimer’s disease (AD) based on 2011 NIA-AA dementia criteria and biomarker criteria (Jack et al, 2018; Jack et al, 2024) which is either: o Confirmation of high likelihood for amyloid pathology consistent with AD, as confirmed by blood-based biomarker (plasma amyloid beta 42 [Aβ42]/40 ratio and phosphorylated-tau217 [p-tau217]/non-phosphorylated- tau217 [p-tau217 ratio], or plasma Aβ42 and Aβ40 concentrations and determination of the presence of apolipoprotein E [ApoE]-specific peptides) at Screening (Visit 1); or o Confirmation of AD by historical documentation of cerebrospinal fluid (CSF) biomarker (CSF Aβ42/40, CSF p-tau181/Aβ42, or CSF total-tau/Aβ42) or amyloid positron emission tomography (PET) brain scan;
6. Meets all of the following criteria for agitation according to the International Psychogeriatric Association (IPA) consensus definition (Sano et al, 2024) at Screening (Visit 1): a. Exhibits one or more of the following persistently or frequently recurring (ie, for a period of ≥ 2 weeks) behaviors associated with observed/inferred evidence of emotional distress (eg, rapid changes in mood, irritability, outbursts): i. Excessive motor activity (eg, includes pacing, rocking, gesturing, pointing fingers, restlessness, performing repetitious mannerisms); and/or ii. Verbal aggression (eg, yelling, speaking in an excessively loud voice, using profanity, screaming, shouting); and/or iii. Physical aggression (eg, grabbing, shoving, pushing, resisting, hitting others, kicking objects or people, scratching, biting, throwing objects, hitting self, slamming doors, tearing things, and destroying property); b. Behaviors produces excess disability, which in the Investigator’s judgment are beyond that due to the cognitive impairment and include at least one of the following: i. Significant impairment in interpersonal relationships; ii. Significant impairment in other aspects of social functioning; or iii. Significant impairment in ability to perform or participate in daily living activities; c. Agitation is not solely attributable to another psychiatric, medical, or environmental condition
7. Has clinically meaningful agitation defined as a Neuropsychiatric Inventory–Agitation/Aggression (NPI-AA) domain total score of ≥ 4 (frequency × severity) at both Screening (Visit 1) and Baseline (Visit 2)
8. Meets criteria for CMAI Factor 1 (verbally and physically aggressive behavior [eg, cursing, screaming, biting, hitting, kicking]) at Screening (Visit 1) and Baseline (Visit 2 ) as specified in Protocol Section 8.1.5: a. ≥ 1 aggressive behavior(s) occurring several times per week; b. ≥ 2 aggressive behaviors occurring once or twice per week; or c. ≥ 3 aggressive behaviors occurring less than once per week.
9. CGI-S score ≥ 4 at Screening (Visit 1) and Baseline (Visit 2)
10. Has a Mini Mental State Examination, 2nd Edition™: Standard Version (MMSE-2®:SV) score of 6 to 24 (inclusive) at Screening (Visit 1)
11. Lives at home or in an assisted living/long-term care facility and has the ability to visit the clinic as an outpatient if the study is not otherwise being conducted at the assisted living or long-term care facility. a. Patients living at home must not live alone; b. Patients must have been at their current location for at least 4 weeks prior to Screening and plan to remain at the same location for the duration of the trial; c. Patients must be accompanied to and from study visits by a designated caregiver

Exclusion criteria 5

1. Agitation symptoms are attributable to concomitant medications, adverse environmental conditions, substance abuse, or active medical or psychiatric conditions as per Investigator’s judgment
2. Has been diagnosed with one or more of the following psychiatric conditions: a. Schizophrenia, schizoaffective disorder, or other psychotic disorder that is not related to Alzheimer’s dementia; b. Bipolar disorder; c. Major depressive disorder, unless it is considered stable and treated for at least 8 weeks prior to Screening (Visit 1)
3. Has a significant risk for suicidal behavior during the course of their participation in the study, or is considered to be an imminent danger to themselves or others, in the opinion of the Investigator, and/or as assessed by Columbia Suicide Severity Rating Scale (C-SSRS); or the patient has had 1 or more suicide attempts within 2 years prior to Screening (Visit 1)
4. The patient has known hypersensitivity or intolerance toITI-1284 or lumateperone, or to any of their excipients.
5. Has had an insufficient response, based on the Investigator’s judgment, to 2 or more previous antipsychotic medications for the treatment of dementia-related agitation

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary efficacy endpoint is the change from baseline to end of Week 12 in CMAI total score.

Secondary endpoints 1

1. The key secondary efficacy endpoint: change from baseline to end of Week 12 in CGI-S score.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Intra-Cellular Therapies Inc.

Sponsor organisation

Intra-Cellular Therapies Inc.

Address

430 East 29th Street Suite 900

City

New York

Postcode

10016-8367

Country

United States

Scientific contact point

Organisation

Intra-Cellular Therapies Inc.

Contact name

ITI Clinical Trials

Public contact point

Organisation

Intra-Cellular Therapies Inc.

Contact name

ITI Clinical Trials

Third parties 8

Locations

6 EU/EEA countries · 35 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 194 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications