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

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] - Mental Disorders [F03]

Trial duration

11 Jul 2025 → ongoing

Decision date (initial)

2025-05-14

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic

To evaluate the efficacy of ITI-1284 administered once daily compared with placebo in the treatment of psychosis in patients with Alzheimer’s disease (AD), as measured by change from baseline to end of Week 6 in the Behavioral Pathology in Alzheimer’s Disease Rating Scale (BEHAVE-AD) psychosis subscale score

Secondary objectives 1

1. To evaluate the efficacy of ITI-1284 administered once daily compared with placebo in the treatment of psychosis in patients with AD, as measured by change from baseline to end of Week 6 in Clinical Global Impression-Severity (CGI-S) score

Conditions and MedDRA coding

Psychosis associated with Alzheimer’s Disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 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.
2. Male or female, ≥ 55 years of age
3. Has a body mass index (BMI) of 18–40 kg/m2 inclusive
4. Meets clinical criteria for AD based on 2011 NIA-AAdementia 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
5. Meets criteria for psychosis in accordance with the International Psychogeriatric Association (IPA) provisional consensus definition at Screening (Visit 1) and Baseline (Visit 2): o Symptom(s) of psychosis were not present prior to the onset of the symptoms of AD-related dementia; to be substantiated by medical records and/or external contacts (eg, physician, family member, professional caregiver); o Symptom(s) of psychosis have been present, at least intermittently, for ≥ 1 month; o Symptoms are severe enough to cause disruption in patients’ and/or others’ ability to accomplish activities of daily functioning;
6. Scoring ≥ 2 on any item of the BEHAVE-AD Part A. Paranoid and Delusional Ideation item and/or Part B. Hallucinations item (ie, psychosis subscale) at Screening and Baseline
7. CGI-S score ≥ 4 at Screening (Visit 1) and Baseline (Visit 2)
8. Mini-Mental State Examination, 2nd Edition™: Standard Version (MMSE-2®:SV) score of 6 to 24 (inclusive) at Screening (Visit 1) with sufficient verbal ability to understand and answer questions and comply with procedures
9. 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. o Patients living at home must not live alone. o Patients must have been at their current location for at least 4 weeks prior to Screening (Visit 1) and plan to remain at the same location for the duration of the trial

Exclusion criteria 9

1. Psychotic symptoms that are primarily attributable to delirium, substance abuse, or another general-medical condition (eg, hypothyroidism) or has been diagnosed with one or more of the following psychiatric conditions: o Schizophrenia, schizoaffective disorder, or other psychotic disorder that is not related to Alzheimer’s dementia; o Bipolar disorder
2. 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 C-SSRS; or the patient has had 1 or more suicide attempts within 2 years prior to Screening (Visit 1)
3. The patient has known hypersensitivity or intolerance to ITI-1284 or lumateperone, or to any of their excipients
4. The patient is receiving cholinesterase inhibitors, memantine, and/or antidepressant therapy initiated less than 8 weeks of Screening (Visit 1)
5. The patient has used 1 of the following under the specified conditions: o any moderate or strong cytochrome P450 3A4 (CYP3A4) inhibitor or any CYP3A4 inducer within 5 half-lives or 14 days prior to Baseline (Visit 2), whichever is longer; o Monoamine oxidase inhibitors within 14 days prior to Baseline (Visit 2)
6. The patient is unable or unwilling to discontinue other drugs with known psychotropic properties or any non-psychotropic drugs with known or potentially significant central nervous system effects. See Section 7.7.2 for additional information
7. The patient is hospitalized or receiving skilled nursing care for any medical condition other than dementia (skilled nursing care includes procedures that can only be administered by a registered nurse or doctor, such as [but not limited to] need for feeding tube, intravenous administration of medication, procedures related to insertion or care of suprapubic catheters, and nasopharyngeal/tracheostomy aspiration)
8. The patient is bedridden or has any significant medical condition that is unstable and that would either: o Place the patient at undue risk from study drug or undergoing study procedures; or o Interfere with the interpretation of safety or efficacy evaluations performed during the course of the study
9. The patient is in hospice or end-of-life care

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. the change from baseline to end of Week 6 in BEHAVE-AD psychosis subscale score

Secondary endpoints 1

1. the change from baseline to end of Week 6 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

135 US Highway 202 206

City

Bedminster

Postcode

07921-2608

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 9

Locations

8 EU/EEA countries · 43 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 258 files

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

Application history

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