NCT04080752

A Study of JNJ-61393215 in the Treatment of Depression

Completed Phase 2 Results posted Last updated 29 April 2025

What this trial tests

Phase 2 trial testing JNJ-61393215 in Major Depressive Disorder With Anxious Distress in 222 participants. Completed in 2 September 2021.

Timeline

17 September 2019

Primary endpoint
2 September 2021

2 September 2021

Quick facts

Lead sponsor	Janssen Research & Development, LLC
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	222
Start date	17 September 2019
Primary completion	2 September 2021
Estimated completion	2 September 2021
Sites	35 locations across Russia, Ukraine, United Kingdom, Moldova, United States

Drugs / interventions tested

• JNJ-61393215 — full drug profile →
• Placebo

Conditions studied

• Major Depressive Disorder With Anxious Distress — all drugs for Major Depressive Disorder With Anxious Distress →

Sponsor

Janssen Research & Development, LLC — full company profile →

Who can join

Adults 18 to 64, any sex, with Major Depressive Disorder With Anxious Distress. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Hamilton Depression Rating Scale-17 (HDRS-17) Total Score at Week 6 Primary · Baseline and Week 6

Change from baseline in HDRS-17 total score at Week 6 was reported. The HDRS-17 is a clinician-administered rating scale designed to assess the severity of symptoms in participants diagnosed with depression with a score range of 0 to 52. Each of the 17 items is rated by the clinician on either a 3-point (0 to 2) or a 5-point scale (0 to 4). The point scale used a rating of 0 (absent), 1 (doubtful to mild), 2 (mild to moderate), 3 (moderate to severe), and 4 (very severe). A total score (range: 0 to 52) was calculated by adding the scores of all 17 items. For each item as well as the total scor

Group	Value	95% CI
Placebo	-8.8	± 0.66
JNJ-61393215 135 Milligrams (mg)	-9.4	± 0.64

Change From Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Score at Week 6 Secondary · Baseline and Week 6

Change from baseline in HAM-A total score at Week 6 was reported. HAM-A is a 14-item scale designed to measure severity of anxiety-related symptoms in participants. Each question reflects a symptom of general anxiety, including physical anxiety and mental anxiety. Each item was rated on a 5-point scale ranged from 0 (not present) to 4 (maximum anxiety). The total score was sum of 14 items scores and it ranged from 0 (normal) to 56 (severe), where higher score indicated greater degree of anxiety symptom. The total score was categorized as 0-13: normal range, 14-17: mild severity, 18-24: mild to

Group	Value	95% CI
Placebo	-10.4	± 0.74
JNJ-61393215 135 Milligrams (mg)	-10.3	± 0.72

Change From Baseline in HAM-A Total Score at Weeks 2 and 4 Secondary · Baseline, Week 2, and Week 4

Change from baseline in HAM-A total score at Weeks 2 and 4 were reported. HAM-A is a 14-item scale designed to measure severity of anxiety-related symptoms in participants. Each question reflects a symptom of general anxiety, including physical anxiety and mental anxiety. Each item was rated on a 5-point scale ranged from 0 (not present) to 4 (maximum anxiety). The total score was sum of 14 items scores and it ranged from 0 (normal) to 56 (severe), where higher score indicated greater degree of anxiety symptom. The total score was categorized as 0-13: normal range, 14-17: mild severity, 18-24:

Week 2

Group	Value	95% CI
Placebo	-4.85	± 0.511
JNJ-61393215 135 Milligrams (mg)	-4.1	± 0.505

Week 4

Group	Value	95% CI
Placebo	-8.05	± 0.616
JNJ-61393215 135 Milligrams (mg)	-7.9	± 0.603

Change From Baseline in HDRS-17 Total Score in Participants With a Baseline HAM-A Score >=20 at Week 6 Secondary · Baseline and Week 6

Change from baseline in HDRS-17 total score in participants with a baseline HAM-A score \>=20 at Week 6 was reported. The HDRS-17 is a clinician-administered rating scale designed to assess the severity of symptoms in participants diagnosed with depression with a score range of 0 to 52. Each of the 17 items is rated by the clinician on either a 3-point (0 to 2) or a 5-point scale (0 to 4). The point scale used a rating of 0 (absent), 1 (doubtful to mild), 2 (mild to moderate), 3 (moderate to severe), and 4 (very severe). A total score (range: 0 to 52) was calculated by adding the scores of all

Group	Value	95% CI
Placebo	-8.8	± 0.68
JNJ-61393215 135 Milligrams (mg)	-9.8	± 0.67

Change From Baseline in HAM-A Total Score in Participants With a Baseline HAM-A Score >=20 at Week 6 Secondary · Baseline and Week 6

Change from baseline in HAM-A total score in participants with a baseline HAM-A score \>=20 at Week 6 was reported. HAM-A is a 14-item scale designed to measure severity of anxiety-related symptoms in participants. Each question reflects a symptom of general anxiety, including physical anxiety and mental anxiety. Each item was rated on a 5-point scale ranged from 0 (not present) to 4 (maximum anxiety). The total score was sum of 14 items scores and it ranged from 0 (normal) to 56 (severe), where higher score indicated greater degree of anxiety symptom. The total score was categorized as 0-13:

Group	Value	95% CI
Placebo	-10.6	± 0.78
JNJ-61393215 135 Milligrams (mg)	-10.9	± 0.77

Change From Baseline in Generalized Anxiety Disorder-7 (GAD-7) Total Score at Week 6 Secondary · Baseline and Week 6

Change from baseline in GAD-7 total score at Week 6 was reported. The GAD-7 is a brief and validated 7-item self-reported assessment of overall anxiety. Participants respond to each item using a 4-point scale with response categories of 0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day. Item responses are summed to yield a total score with a range of 0 to 21, where higher scores indicate more anxiety. The recall period is 2 weeks. The severity of the GAD-7 is categorized as follows: None (0-4), Mild (5-9), Moderate (10-14) and Severe (15-21).

Group	Value	95% CI
Placebo	-5.3	± 0.52
JNJ-61393215 135 Milligrams (mg)	-5.7	± 0.51

Change From Baseline in Patient Health Questionnaire (PHQ-9) Total Score at Weeks 2 and 4 Secondary · Baseline, Week 2, and Week 4

Change From baseline in PHQ-9 total score at Weeks 2 and 4. The PHQ-9 is a 9-item, Patient Reported Outcome (PRO) measure to assess depressive symptoms. The scale scores each of the 9 symptom domains of the Diagnostic and Statistical Manual of Mental Disorders-5th Edition (DSM-5) major depressive disorder (MDD) criteria. Each item is rated on a 4 point scale (0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day). The participants item responses are summed to provide a total score (range of 0 to 27), with higher scores indicating greater severity of depressive symptom

Week 2

Group	Value	95% CI
Placebo	-3.26	± 0.461
JNJ-61393215 135 Milligrams (mg)	-2.84	± 0.455

Week 4

Group	Value	95% CI
Placebo	-5.63	± 0.557
JNJ-61393215 135 Milligrams (mg)	-5.71	± 0.544

Change From Baseline in HDRS-17 Total Score at Weeks 2 and 4 Secondary · Baseline, Week 2, and Week 4

Change From baseline in HDRS-17 total score at Weeks 2 and 4. The HDRS-17 is a clinician-administered rating scale designed to assess the severity of symptoms in participants diagnosed with depression with a score range of 0 to 52. Each of the 17 items is rated by the clinician on either a 3-point (0 to 2) or a 5-point scale (0 to 4). The point scale used a rating of 0 (absent), 1 (doubtful to mild), 2 (mild to moderate), 3 (moderate to severe), and 4 (very severe). A total score (range: 0 to 52) was calculated by adding the scores of all 17 items. For each item as well as the total score, a h

Week 2

Group	Value	95% CI
Placebo	-3.98	± 0.47
JNJ-61393215 135 Milligrams (mg)	-3.54	± 0.465

Week 4

Group	Value	95% CI
Placebo	-6.78	± 0.546
JNJ-61393215 135 Milligrams (mg)	-7.03	± 0.536

Number of Participants With Treatment-emergent Adverse Events (TEAEs) as a Measure of Safety and Tolerability Secondary · Up to 8 weeks

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were events during the initiation of study drug up till follow-up period.

Group	Value	95% CI
Placebo	34
JNJ-61393215 135 Milligrams (mg)	50

Total Plasma Concentration of JNJ-61393215 Secondary · 1-4 hours postdose on Day 1; Predose and 1-4 hours post dose on Days 15, 29, and 43

Total plasma concentration of JNJ-61393215 was reported. The concentrations of JNJ-61393215 were measured using a validated, specific, and sensitive liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method.

Day 1: 1-4 hours postdose

Group	Value	95% CI
JNJ-61393215 135 Milligrams (mg)	4143	± 2315

Day 15: Predose

Group	Value	95% CI
JNJ-61393215 135 Milligrams (mg)	3053	± 1857

Day 15: 1-4 hours postdose

Group	Value	95% CI
JNJ-61393215 135 Milligrams (mg)	5638	± 2362

Day 29: Predose

Group	Value	95% CI
JNJ-61393215 135 Milligrams (mg)	3104	± 1839

Day 29: 1-4 hours postdose

Group	Value	95% CI
JNJ-61393215 135 Milligrams (mg)	5868	± 2267

Day 43: Predose

Group	Value	95% CI
JNJ-61393215 135 Milligrams (mg)	3019	± 1794

Day 43: 1-4 hours postdose

Group	Value	95% CI
JNJ-61393215 135 Milligrams (mg)	5897	± 2288

Plasma Protein Binding (PPB): Percentage of JNJ-61393215 Unbound Secondary · Predose and 1-4 hours post dose on Day 43

Percentage of JNJ-61393215 unbound was determined by using a liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method. The protein binding was assessed by spiking plasma samples with radiolabeled JNJ-61393215.

Day 43: Predose

Group	Value	95% CI
JNJ-61393215 135 Milligrams (mg)	2.52	± 0.776

Day 43: 1-4 hours postdose

Group	Value	95% CI
JNJ-61393215 135 Milligrams (mg)	4.15	± 1.58

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 8 weeks. Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 0/112 (0%)

Deaths: 0/112

JNJ-61393215 135 Milligrams (mg)

Serious: 0/110 (0%)

Deaths: 0/110

Other adverse events (7 terms — click to expand)

Reaction	System	Placebo	JNJ-61393215 135 Milligram…
Headache	Nervous system disorders	—	—
Somnolence	Nervous system disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Abdominal Pain	Gastrointestinal disorders	—	—
Fatigue	General disorders	—	—
Urinary Tract Infection	Infections and infestations	—	—

Data from ClinicalTrials.gov NCT04080752 adverse events section.

Sponsor's own description

The purpose of this study is to evaluate the efficacy of JNJ-61393215 as adjunctive treatment compared to adjunctive placebo, as assessed by the change from baseline to week 6 on a 17-item Hamilton Depression Rating Scale (HDRS-17) in participants with major depressive disorder (MDD) with anxious distress with a score greater than or equal to (\>=) 2 on item 26 or 27 of the Inventory of Depressive Symptomatology, Clinician Rating -30 (IDS-C30), who have a suboptimal response to current treatment with a standard antidepressant.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Selective Orexin Receptor Antagonists as Novel Augmentation Treatments for Major Depressive Disorder: Evidence for Safety and Efficacy From a Phase 2B Study of Seltorexant.
   Jha MK. · · 2022 · cited 5× · PMID 34791262 · DOI 10.1093/ijnp/pyab078
2. Efficacy, safety, and tolerability of JNJ-61393215 (tebideutorexant), a selective orexin-1 receptor antagonist, as adjunctive treatment for major depressive disorder with anxious distress: A double-blind, placebo-controlled, randomized phase 2a study.
   Schmidt ME, Moyer JA, Kezic I, Zhou X, et al · · 2025 · cited 3× · PMID 40215570 · DOI 10.1016/j.euroneuro.2025.03.007