A study to assess the efficacy and safety of ITI-1284 as monotherapy treatment in patients with Generalized Anxiety Disorder

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

21 Jul 2025 → ongoing

Decision date (initial)

2025-06-09

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Intra-Cellular Therapies, Inc.

External identifiers

EU CT number

2024-516684-82-00

ClinicalTrials.gov

NCT06701903

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Therapy, Efficacy, Safety

The primary efficacy objective of this study is to evaluate the efficacy of 2 doses of ITI-1284 (10 mg and 20 mg) administered once daily as monotherapy compared with placebo in patients with GAD who have had inadequate response to GAD treatment, as measured by change from baseline to end of Week 6 in Hamilton Anxiety Rating Scale (HAM-A) total score.

Secondary objectives 1

1. The key secondary efficacy objective of this study is to evaluate the efficacy of 2 doses of ITI-1284 (10 mg and 20 mg) administered once daily as monotherapy compared with placebo in patients with GAD who have had inadequate response to GAD treatment, as measured by change from baseline to end of Week 6 in Clinical Global Impression-Severity (CGI-S) score.

Conditions and MedDRA coding

Generalized Anxiety Disorder

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Provide written informed consent before the initiation of any study specific procedures; NOTE: Patients who are unable to provide informed consent on their own, including those that are under guardianship or curatorship, will be ineligible to participate in this study.
2. Male or female patients ≥ 18 years of age
3. Has a body mass index (BMI) of 19-40 kg/m2 , inclusive
4. At Screening (Visit 1), meet DSM-5-TR diagnostic criteria for moderate or severe Generalized Anxiety Disorder as confirmed by the Investigator or Sponsor-approved rater using the SCID-5-CT, and meets all of the following at Screening (Visit 1) and Baseline (Visit 2): a. HAM-A Total score of ≥ 22; b. HAM-A Items 1 (anxious mood) and 2 (tension) scores ≥ 2; c. CGI-S score of ≥ 4; d. At Baseline (Visit 2) ≤ 25% improvement in HAM-A total score from that at Screening (Visit 1)
5. History of inadequate response (< 50% improvement in anxiety symptoms as measured by the modified ATRQ for GAD) to at least 2 of the following GAD-approved treatments: paroxetine, venlafaxine XR, duloxetine, escitalopram, or buspirone taken at an adequate dose (at least the minimum GAD-approved dose per package insert) and duration (ie, for at least 6 weeks prior to Screening [Visit 1]) for the treatment of ongoing GAD symptoms
6. Is currently an outpatient, and is anticipated to maintain outpatient status for the duration of the study
7. Male or female of childbearing potential and agrees to use a highly effective method of birth control (defined as those methods, alone or in combination, which result in a failure rate less than 1 percent per year when used consistently and correctly as listed in Appendix II), from the time informed consent is provided through the end of the SFU period. Abstinence may be an acceptable form of birth control based on the Investigator’s judgment and familiarity with the patient’s “preferred and usual lifestyle”; NOTE: Females of non-childbearing potential (defined as either permanently sterilized) or post-menopausal females (defined as at least one year with no menses without an alternative medical explanation) are exempt from the birth control requirement. As per Investigator’s judgment, females with exclusively same sex partners are also exempt from the birth control requirement.
8. Ability to follow study instructions and likely to complete all required visits.
9. Applicable to Czech Republic Only: Patient has a caregiver who is willing to sign the patient information leaflet (informed consent form) and is familiar with the circumstances of the patient’s participation in the clinical trial and able to monitor their compliance and safety during their contact at least 5 times a week.

Exclusion criteria 12

1. Within the patient’s lifetime, has one of the following confirmed DSM-5-TR psychiatric diagnoses: a. Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder or other psychotic disorder; b. Bipolar Disorder
2. Within 6 months of Screening (Visit 1), has a confirmed DSM-5-TR psychiatric diagnosis other than GAD, including: a. Other anxiety disorders (except simple phobias and social anxiety disorder); b. Moderate or severe alcohol or substance use disorders (excluding nicotine); c. Moderate or severe major depressive disorder (MDD); d. Any other psychiatric condition (except for mild MDD) that has been the main focus of treatment or of sufficient severity to have a major impact on the patient’s psychiatric status
3. MADRS total score > 18 at Screening (Visit 1) or Baseline (Visit 2)
4. In the opinion of the Investigator, the patient has a significant risk for suicidal behavior during his/her participation in the study or a. At Screening (Visit 1), the patient scores “yes” on Suicidal Ideation Items 4 or 5 of the C-SSRS within 6 months prior to Screening (Visit 1) or, at Baseline (Visit 2), the patient scores “yes” on Suicidal Ideation Items 4 or 5 since the screening visit; b. At Screening (Visit 1), the patient has had 1 or more suicidal attempts within the 2 years prior to Screening; c. At Screening (Visit 1) or Baseline (Visit 2) MADRS Item 10 score ≥ 5; or d. The patient is considered to be an imminent danger to him/herself or others based on the assessment of the Investigator
5. Lifetime history of failure to respond to > 3 of the approved treatments for GAD (ie, paroxetine, venlafaxine XR, duloxetine, escitalopram, or buspirone) at an adequate dose (ie, at least the minimum dose approved for GAD per package insert) and for an adequate duration (ie, at least 6 weeks)
6. The patient has received electroconvulsive therapy (ECT) or vagal nerve stimulation within the past 5 years, or repetitive trans-cranial magnetic stimulation within the last 2 years prior to Screening (Visit 1), or had a failure in response to ECT at any time
7. The patient has known hypersensitivity or intolerance to ITI-1284 or lumateperone, or to any of their excipients
8. The patient has plans to initiate psychotherapy during the study; ongoing psychotherapy that has been stable (at least 2 months) prior to Baseline (Visit 2) is permissible
9. The patient is unable to be safely discontinued or unwilling to discontinue benzodiazepine treatment at least 2 days prior to Baseline (Visit 2)
10. The patient has used 1 of the following agents under the specified conditions: a. 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); b. Monoamine oxidase inhibitors within 14 days prior to Baseline (Visit 2)
11. The patient is unable to be safely discontinued or unwilling to discontinue other drugs with known psychotropic properties or any non-psychotropic drugs with known or potentially significant central nervous system effects, in the opinion of the Investigator, before Baseline (Visit 2), including, but not limited to: a. Sedative hypnotics; b. Central opioid agonists/antagonists including tramadol; c. Anticonvulsants, mood stabilizers, antidepressants, stimulants, antipsychotics, and nonbenzodiazepine anxiolytics
12. Please refer to the Protocol for additional exclusion criteria.

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 6 in HAM-A total score.

Secondary endpoints 2

1. The key secondary efficacy endpoint is the change from baseline to end of Week 6 in CGI-S score.
2. Additional secondary efficacy endpoints include by visit, change from baseline in HAM-A total score; CGI-S score; Q-LES-Q score; ≥ 50% reduction from baseline in HAM-A total score; HAM-A remission (HAM-A total score ≤ 7); CGI-I scale score; change from baseline in MADRS total score; PGI-C scale 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 6

Locations

5 EU/EEA countries · 29 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 106 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