A Study of Lumateperone Versus Placebo in Participants With Major Depressive Disorder (CANDLE)

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Assess the Efficacy and Safety of Fixed Doses of Lumateperone Administered as Monotherapy in Participants With Major Depressive Disorder and an Open-label Long-term Extension Treatment With Lumateperone

The purpose of the study is to assess how well each dose of lumateperone (Dose 1 and 2) works when given alone as compared to placebo in participants with major depressive disorder (MDD; a medical condition characterized by a persistent feeling of deep sadness, hopelessness, and a loss of interest in activities for a prolonged period of time and interfere with ability to function).

Study Overview

• Status: Not yet recruiting
• Conditions: Depressive Disorder, Major
• Intervention / Treatment: Drug: Lumateperone; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 585
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Study Contact; Phone Number: 844-434-4210; Email: Participate-In-This-Study1@its.jnj.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Medically stable based on physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening and where applicable at DB period baseline
• Medically stable based on clinical laboratory tests performed at screening and where applicable at DB period baseline
• Meets the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) diagnostic criteria for recurrent or single episode MDD, without psychotic features, based upon clinical assessment and confirmed by Structured Clinical Interview for DSM-5 Axis I Disorders - Clinical Trials Version (SCID-CT)
• Has moderate-to-severe depression as measured by a rater-administered MADRS total greater than or equal to (>=) 26 score and corresponding to a CGI-S score of >=4 at screening and DB baseline
• Has a Quick Inventory of Depressive Symptomatology-Self Report-16 item (QIDS-SR-16) score of >=15 at screening and DB baseline

Exclusion criteria:

• The participant experiences a >=25 percent (%) decrease in the MADRS total score between screening and DB baseline
• The participant experiences a >=25% decrease in the QIDS-SR-16 total score between screening and DB baseline
• Has homicidal ideation/intent, per the investigator's clinical judgment, or has suicidal ideation with some intent to act within 3 months prior to the start of the screening period, per the investigator's clinical judgment or based on the Columbia-Suicide Severity Rating Scale (C-SSRS), corresponding to a response of "Yes" on Item 4 (active suicidal ideation with some intent to act, without specific plan) or Item 5 (active suicidal ideation with specific plan and intent) for suicidal ideation on the C-SSRS, or a history of suicidal behavior within the past 6 months prior to the start of the screening period
• Has a history of moderate-to-severe substance use disorder including alcohol use disorder according to DSM-5 criteria within 6 months before screening
• Has a history or evidence of clinically meaningful noncompliance with antidepressant therapy (ADT)s

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lumateperone: Dose 1; Eligible participants will receive dose 1 of lumateperone once daily starting on Day 1 of Double-blind (DB) treatment period for up to 6 weeks. At Visit Week 6, participants who completed DB Treatment Period, may have the option to roll over into an open-label (OL) treatment period to receive dose 1 or dose 2 of lumateperone for up to 24 weeks.	Drug: Lumateperone; Participants will receive lumateperone orally.; Other Names: Caplyta
Experimental: Lumateperone: Dose 2; Eligible participants will receive dose 2 of lumateperone once daily starting on Day 1 of DB treatment period for up to 6 weeks. At Visit Week 6, participants who completed DB Treatment Period, may have the option to roll over into an OL treatment period to receive dose 1 or dose 2 of lumateperone for up to 24 weeks.	Drug: Lumateperone; Participants will receive lumateperone orally.; Other Names: Caplyta
Placebo Comparator: Placebo; Eligible participants will receive placebo once daily starting on Day 1 of DB treatment period for up to 6 weeks. At Visit Week 6, participants who complete the DB treatment period, may have the option to participate in OL treatment period to receive dose 1 or dose 2 of lumateperone for up to 24 weeks.	Drug: Lumateperone; Participants will receive lumateperone orally.; Other Names: Caplyta; Drug: Placebo; Participants will receive placebo orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from DB Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score to End of Week 6	The MADRS is a 10-item clinician-rated scale designed to measure the overall severity of depressive symptoms. The MADRS total score ranges from 0 to 60 where higher score indicates more severity in symptoms.	DB Baseline (Day 1) up to Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from DB Baseline in Clinical Global Impression-Severity (CGI-S) Score to Week 6	The CGI-S evaluates the severity of participant's depressive symptoms on a scale of 0 to 7. Considering total clinical experience, a participant is assessed on severity of mental illness at the time of rating according to: 0=not assessed; 1=normal (not at all ill); 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill participants.	DB Baseline (Day 1) up to Week 6
Change from DB Baseline in MADRS Total Score to Week 2	The MADRS is a 10-item clinician-rated scale designed to measure the overall severity of depressive symptoms. The MADRS total score ranges from 0 to 60 where higher score indicates more severity in symptoms.	DB Baseline (Day 1) up to Week 2
Change from DB Baseline in MADRS Total Score to Week 1	The MADRS is a 10-item clinician-rated scale designed to measure the overall severity of depressive symptoms. The MADRS total score ranges from 0 to 60 where higher score indicates more severity in symptoms.	DB Baseline (Day 1) up to Week 1

Collaborators and Investigators

• Sponsor: Intra-Cellular Therapies, Inc.
• Investigators: Study Director: Intra-Cellular Therapies, Inc. Clinical Trial, Intra-Cellular Therapies, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): October 20, 2026
• Primary Completion (Estimated): September 20, 2029
• Study Completion (Estimated): September 20, 2029

Study Registration Dates

• First Submitted: July 30, 2026
• First Submitted That Met QC Criteria: July 30, 2026
• First Posted (Actual): August 5, 2026

Study Record Updates

• Last Update Posted (Actual): August 31, 2026
• Last Update Submitted That Met QC Criteria: August 27, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major; lumateperone
• Other Study ID Numbers: 86952580MDD3001; 2026-525307-27-00 (Registry Identifier: EUCT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of Johnson & Johnson Innovative Medicine is available at innovativemedicine.jnj.com/our-innovation/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

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