Clinical Trial Results:
A Randomized, Stratified, Double-blind, Placebo-Controlled Study to Investigate the Efficacy, Safety and Tolerability of JNJ-55308942 in Bipolar Depression
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Summary
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EudraCT number |
2021-004790-31 |
Trial protocol |
ES PL |
Global end of trial date |
17 May 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
30 May 2025
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First version publication date |
30 May 2025
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
55308942BIP2001
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT05328297 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Janssen Research & Development LLC
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Sponsor organisation address |
920 Route 202 South, Raritan New Jersey, United States, 08869
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Public contact |
Clinical Registry Group, Janssen Research & Development LLC, ClinicalTrialsEU@its.jnj.com
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Scientific contact |
Clinical Registry Group, Janssen Research & Development LLC, ClinicalTrialsEU@its.jnj.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
17 May 2024
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
17 May 2024
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The main objective of the trial was to evaluate the efficacy of JNJ-55308942 compared to placebo on symptoms of depression in subjects with bipolar disorder (BD) in an major depressive episode (MDE) at Week 6.
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Protection of trial subjects |
This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practices and applicable regulatory requirements.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
03 Jun 2022
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Canada: 1
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Country: Number of subjects enrolled |
Poland: 60
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Country: Number of subjects enrolled |
Spain: 7
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Country: Number of subjects enrolled |
United States: 46
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Worldwide total number of subjects |
114
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EEA total number of subjects |
67
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
114
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
A total of 116 subjects were randomised in this study, out of which 114 received treatment. Out of 114 subjects, 92 completed the study. | |||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
A total of 116 subjects were randomised in this study, out of which 114 received treatment. Out of 114 subjects, 92 completed the study. | |||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | |||||||||||||||||||||||||||
Blinding implementation details |
Subjects and investigators were blinded to treatment.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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JNJ-55308942 | |||||||||||||||||||||||||||
Arm description |
During double-blind (DB) treatment phase, subjects received JNJ-55308942 capsule, orally once daily from Day 1 (Week 0) up to 6 weeks. Subjects were then followed up for up to 2 weeks after their last dose (up to Day 56). | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
JNJ-55308942
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
A single JNJ-55308942 capsule once daily from Day 1 up to 6 weeks during DB phase.
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Arm title
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Placebo | |||||||||||||||||||||||||||
Arm description |
During DB treatment phase, subjects received placebo capsule (matching to JNJ-55308942), orally once daily from Day 1 (Week 0) up to 6 weeks. Subjects were then followed up for up to 2 weeks after their last dose (up to Day 56). | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
A single JNJ-55308942 matching placebo capsule once daily from Day 1 up to 6 weeks during DB phase.
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Baseline characteristics reporting groups
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Reporting group title |
JNJ-55308942
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Reporting group description |
During double-blind (DB) treatment phase, subjects received JNJ-55308942 capsule, orally once daily from Day 1 (Week 0) up to 6 weeks. Subjects were then followed up for up to 2 weeks after their last dose (up to Day 56). | ||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
During DB treatment phase, subjects received placebo capsule (matching to JNJ-55308942), orally once daily from Day 1 (Week 0) up to 6 weeks. Subjects were then followed up for up to 2 weeks after their last dose (up to Day 56). | ||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
JNJ-55308942
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Reporting group description |
During double-blind (DB) treatment phase, subjects received JNJ-55308942 capsule, orally once daily from Day 1 (Week 0) up to 6 weeks. Subjects were then followed up for up to 2 weeks after their last dose (up to Day 56). | ||
Reporting group title |
Placebo
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Reporting group description |
During DB treatment phase, subjects received placebo capsule (matching to JNJ-55308942), orally once daily from Day 1 (Week 0) up to 6 weeks. Subjects were then followed up for up to 2 weeks after their last dose (up to Day 56). | ||
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End point title |
Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score up to Week 6 | ||||||||||||
End point description |
MADRS was a clinician-rated scale designed to measure depression severity and detect changes due to antidepressant (AD) treatment. MADRS evaluated reported sadness, apparent sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. The scale consisted 10 items, each was scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms), with higher score indicating more severe condition. MADRS total score was the sum of scores from individual question items and it ranged from 0 to 60, with higher scores indicated more severe conditions. Negative change in MADRS total score indicated improvement. Full analysis set (FAS) included all randomised subjects who received at least 1 dose of study intervention and had both baseline and at least 1 postbaseline MADRS measurement.
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End point type |
Primary
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End point timeframe |
From Baseline (Day 1) up to Week 6
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Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Statistical analysis description |
Statistical Analysis 1
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Comparison groups |
JNJ-55308942 v Placebo
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Number of subjects included in analysis |
107
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.438 | ||||||||||||
Method |
Mixed Model for Repeated Measures (MMRM) | ||||||||||||
Parameter type |
Least Square Mean difference | ||||||||||||
Point estimate |
-0.3
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Confidence interval |
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80% | ||||||||||||
sides |
2-sided
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lower limit |
-2.84 | ||||||||||||
upper limit |
2.23 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
1.96
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End point title |
Change from Baseline in Snaith-Hamilton Pleasure Scale (SHAPS) Total Score up to Week 6 | ||||||||||||
End point description |
Change from baseline in SHAPS total score up to Week 6 were reported. The SHAPS was a reliable, valid, and unidimensional instrument used to assess hedonic capacity in adults with Major Depressive Disorder (MDD). It is a 14-item, self-report tool with a completion time below 5 minutes. Each of the items had a set of 4 response categories: 1 = definitely agree/strongly agree, 2 = agree, 3 = disagree, and 4 = strongly disagree. The SHAPS total score was the sum of the 14 item scores, which ranged from 14 to 56. A higher SHAPS total score indicated higher levels of current anhedonia. Negative changes in the SHAPS total score indicated improvement. FAS included all randomised subjects who received at least 1 dose of study intervention and had both baseline and at least 1 postbaseline MADRS measurement. Here, 'N' (subjects analysed) signifies number of subjects evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
From Baseline (Day 1) up to Week 6
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from Baseline in MADRS Total Score up to Week 6 (Diagnosis Subgroup Analysis) | ||||||||||||||||||
End point description |
Diagnosis subgroup analysis included subjects with bipolar type I or II. MADRS was clinician-rated scale designed to measure depression severity and detect changes due to AD treatment. MADRS evaluated reported sadness, apparent sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Scale consist 10 items, each scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms); higher score indicated more severe condition. MADRS total score was sum of scores from individual question items and ranged from 0-60; higher scores indicated more severe conditions. Negative change in MADRS total score indicated improvement. FAS was used. 'N' (subjects analysed): number of subjects evaluable for this endpoint and 'n' (number analysed): subjects analysed at specified categories.
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End point type |
Secondary
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End point timeframe |
From Baseline (Day 1) up to Week 6
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Change from Baseline in MADRS Total Score up to Week 6 (Genetic Subgroup Analysis) | ||||||||||||||||||
End point description |
Genetic subgroup analysis: subjects with bipolar depression with P2RX7 Gain of Function single nucleotide polymorphism mutation genotype: heterozygous or homozygous. MADRS was clinician-rated scale designed to measure depression severity and detect changes due to AD treatment. MADRS evaluated reported sadness, apparent sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Scale consist 10 items, each scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms); higher score indicated more severe condition. MADRS total score was sum of scores from individual question items and ranged from 0-60; higher scores indicated more severe conditions. Negative change in MADRS total score indicated improvement. FAS was used. 'N' (subjects analysed):number of subjects evaluable for this endpoint and 'n' (number analysed):subjects analysed at specified categories.
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End point type |
Secondary
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End point timeframe |
From Baseline (Day 1) up to Week 6
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Change from Baseline in MADRS Total Score up to Week 6 (Biomarker Subgroup Analysis) | ||||||||||||||||||
End point description |
Biomarker subgroup analysis included specific (3-Marker Model [3MM]) biomarker profile: Yes or No. 3MM biomarker profile: serum C-reactive protein >3 mg/Liter(L) and soluble interleukin-6 receptor >25 micrograms(mcg)/L or tumor necrosis factor >4 nanograms(ng)/L at baseline. MADRS evaluated reported sadness, apparent sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Scale consist 10 items, each scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms); higher score indicated more severe condition. MADRS total score was sum of scores from individual question items and ranged from 0-60; higher scores indicated more severe conditions. Negative change in MADRS total score indicated improvement. FAS was used. 'N' (subjects analysed): number of subjects evaluable for this endpoint and 'n' (number analysed): subjects analysed at specified categories.
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End point type |
Secondary
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End point timeframe |
From Baseline (Day 1) up to Week 6
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Number of Subjects with Treatment-emergent Clinically Important Abnormalities in Vital Signs | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Vital signs included pulse rate (abnormally low [AL]:<50 beats per minute[bpm] with >15 bpm decrease from baseline and abnormally high [AH]: >100 bpm with >15 bpm increase from baseline),Systolic blood pressure (SBP; AL: <90 millimeters of mercury[mmHg] with >20 mmHg decrease from baseline and AH: >180 mmHg with >20 mmHg increase from baseline), Diastolic BP (DBP; AL: <50 mmHg with >15 mmHg decrease from baseline and AH: >105 mmHg with >15 mmHg increase from baseline), temperature (AL: <35.5 and AH: >37.5 degree Celsius [C]), respiratory rate (AH: >20 breaths per minute),and weight (planned to analyzed at Weeks 6 and 8 only; AL: decrease from baseline >7% and AH: increase from baseline >7%). TE abnormalities in vital signs: those abnormalities that occurred at or after first dose administration. Safety analysis set: all randomised subjects who took at least 1 dose of study intervention. ‘N’: number of subjects evaluable for this endpoint. 'n': subject analysed at specified categories.
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End point type |
Secondary
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End point timeframe |
Weeks 1, 2, 4, 6, and 8 (Follow-up/Early Withdrawal)
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Change From Baseline in Clinical Laboratory Values in Male Hormone: Inhibin B | |||||||||||||||||||||
End point description |
Change from baseline in clinical laboratory values in male hormone (Inhibin B) were reported. Safety analysis set included all randomised subjects who took at least 1 dose of study intervention. Here, 'N' (subjects analysed) signifies number of subjects evaluable for this endpoint. Here, 'n' (number analysed) is defined as subjects analysed at specified timepoints.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1), Week 4, 6, and 8 (Follow-up/Early Withdrawal)
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Change From Baseline in Clinical Laboratory Values in Male Hormone: Luteinizing Hormone | |||||||||||||||||||||
End point description |
Change from baseline in clinical laboratory values in male hormone (luteinizing hormone) were reported. Safety analysis set included all randomised subjects who took at least 1 dose of study intervention. Here, 'N' (subjects analysed) signifies number of subjects evaluable for this endpoint. Here, 'n' (number analysed) is defined as subjects analysed at specified timepoints.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1), Week 4, 6, and 8 (Follow-up/Early Withdrawal)
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Change From Baseline in Clinical Laboratory Values in Male Hormone: Prolactin | |||||||||||||||||||||
End point description |
Change from baseline in clinical laboratory values in male hormone (prolactin) were reported. Safety analysis set included all randomised subjects who took at least 1 dose of study intervention. Here, 'N' (subjects analysed) signifies number of subjects evaluable for this endpoint. Here, 'n' (number analysed) is defined as subjects analysed at specified timepoints.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1), Weeks 4, 6, and 8 (Follow-up/Early Withdrawal)
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Change From Baseline in Clinical Laboratory Values in Male Hormones: Sex Hormone Binding Globulin, Testosterone (Free), Testosterone (High Sensitivity), and Testosterone (Low Sensitivity) | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Change from baseline in clinical laboratory values in male hormones (sex hormone binding globulin, testosterone [free], testosterone [high sensitivity], and testosterone [low sensitivity]) were reported. Safety analysis set included all randomised subjects who took at least 1 dose of study intervention. Here, 'N' (subjects analysed) signifies number of subjects evaluable for this endpoint. Here, 'n' (number analysed) is defined as subjects analysed at specified categories.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1), Weeks 4, 6, and 8 (Follow-up/Early Withdrawal)
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Number of Subjects With Abnormal Laboratory Values: Serum Chemistry | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Number of subjects with abnormal laboratory values: serum chemistry were reported. It included: aspartate aminotransferase (high), alanine aminotransferase (high), bilirubin (high/low), and alkaline phosphatase (high/low). Only categories with data were reported. Safety analysis set included all randomised subjects who took at least 1 dose of study intervention. Here, 'n' (number analysed) is defined as subjects analysed at specified categories.
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End point type |
Secondary
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End point timeframe |
Weeks 2, 4, 6, and 8 (Follow-up/Early Withdrawal)
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Number of Subjects With Clinically Significant Abnormal Laboratory Values: Hematology | |||||||||||||||||||||
End point description |
Number of subjects with clinically significant abnormal laboratory values: hematology were reported. Safety analysis set included all randomised subjects who took at least 1 dose of study intervention.
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End point type |
Secondary
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End point timeframe |
Weeks 2, 4, 6, and 8 (Follow-up/Early Withdrawal)
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Number of Subjects With Clinically Significant Abnormal Laboratory Values: Urinalysis | |||||||||||||||||||||
End point description |
Number of subjects with clinically significant abnormal laboratory values: urinalysis were reported. Safety analysis set included all randomised subjects who took at least 1 dose of study intervention.
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End point type |
Secondary
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End point timeframe |
Weeks 2, 4, 6, and 8 (Follow-up/Early Withdrawal)
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Number of Subjects with Treatment-emergent Adverse Events (TEAEs) | |||||||||
End point description |
Number of subjects with TEAEs were reported. An adverse event (AE) is any untoward medical occurrence in a clinical study subjects who administered a medicinal (investigational or non-investigational) product and does not necessarily have a causal relationship with the treatment. A TEAE defined as an AE that occurred at or after the first dose administration up to day of the last dose plus 30 days. Safety analysis set included all randomized subjects who took at least 1 dose of study intervention.
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End point type |
Secondary
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End point timeframe |
Day 1 (Week 0) up to 30 days after the last dose (up to 11 weeks)
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of Subjects with Treatment-emergent Abnormalities in Electrocardiograms (ECGs) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Number of subjects with treatment-emergent abnormalities in ECGs were reported. It included ECG mean heart rate (abnormally low [AL]: <50 and abnormally high [AH]: >100 beats per minute [bpm]), PR Interval (AL: <120 and AH: >200 milliseconds [msec]), QRS Duration (AL: <60 and AH: >120 msec), and QT Interval (AL: <200 and AH: >500 msec). Treatment-emergent abnormalities in ECGs is defined as those abnormalities that occurred at or after the first dose administration. Safety analysis set included all randomised subjects who took at least 1 dose of study intervention. Here, 'n' (number analysed) is defined as subjects analysed at specified categories.
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End point type |
Secondary
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End point timeframe |
Weeks 1, 2, 4, 6, and 8 (Follow-up/Early Withdrawal)
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Change from Baseline in Young Mania Rating Scale (YMRS) Total Score | ||||||||||||
End point description |
Change from baseline in YMRS total score were reported. The YMRS was designed to measure the severity of manic symptoms, to gauge the effect of treatment on mania severity, and to detect a return of manic symptoms (for example relapse or recurrence). YMRS had 11 items : 4 items (irritability, speech, thought content, and disruptive/aggressive behavior) were graded on a scale of 0 to 8 and the remaining 7 items (elevated mood, increased motor activity, sexual interest, sleep, language-thought disorder, appearance, and insight) were graded on a scale of 0 to 4. Higher scores indicated greater symptom severity. Responses were summed to yield YMRS total score ranged from 0 to 60 , with higher scores reflecting greater severity of mania. Safety analysis set included all randomised subjects who took at least 1 dose of study intervention. Here, 'N' (subjects analysed) signifies number of subjects evaluable for this endpoint.
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End point type |
Secondary
|
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End point timeframe |
From Baseline (Day 1) up to Week 6
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of Subjects Who Reported Suicidal Ideation (SI) or Suicidal Behavior (SB) Using With Columbia Suicide Severity Rating Scale (C-SSRS) Score | ||||||||||||||||||
End point description |
C-SSRS is a clinician-rated instrument that reports severity of both SI and SB. SI categories : 1 (wish to be dead), 2 (nonspecific active suicidal thoughts), 3 (active SI with any methods [not plan] without intent to act), 4 (active SI with some intent to act, without specific plan), and 5 (active SI with specific plan and intent). SB categories: 6 (preparatory acts or behavior), 7 (aborted attempt), 8 (interrupted attempt), 9 (actual attempt), and 10 (suicide). An additional category for non-suicide: non-suicidal self-injurious behavior. SI/SB was indicated by "yes" answer to any listed categories. Score of 0 (no SI/SB) was assigned. Maximum score of 1 to 10 was assigned if SI/SB was present. Scoring was grouped into 3 categories: No SI or behavior (0), SI (score 1 to 5), and SB (score 6 to 10), with higher scores indicating more severe ideation/behavior. Safety set was used. Here, 'N' (subjects analysed) signifies number of subjects evaluable for this endpoint.
|
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End point type |
Secondary
|
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End point timeframe |
From Baseline (Day 1) up to Week 8
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| No statistical analyses for this end point | |||||||||||||||||||
|
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End point title |
Change from Baseline in Clinical Global Impression-Severity Scale (CGI-S) Score | ||||||||||||
End point description |
Change from baseline in CGI-S score were reported. The CGI-S provides an overall clinician-determined summary measure of the severity of the subject's illness that takes into account all available information, including knowledge of the subject's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the subject's ability to function. The CGI-S is a 7-point global assessment scale that measures the clinician's impression of the severity of mental illness exhibited by a subject, and rated on a scale of 1 to 7: 1=normal (not at all ill); 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; and 7=among the most extremely ill subjects. Higher scores indicate worsening. Negative change in CGI-S score indicate improvement. Safety analysis set included all randomised subjects who took at least 1 dose of study intervention. Here, 'N' (subjects analysed) signifies number of subjects evaluable for this endpoint.
|
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End point type |
Secondary
|
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End point timeframe |
From Baseline (Day 1) up to Week 6
|
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|
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| No statistical analyses for this end point | |||||||||||||
|
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End point title |
Plasma Concentrations of JNJ-55308942 [1] | ||||||||||||||||||||||||||||||||||||||
End point description |
Plasma concentrations of JNJ-55308942 were reported. Pharmacokinetics (PK) analysis set included all subjects who received at least 1 dose of JNJ-55308942 and had at least 1 valid blood sample drawn for PK analysis. Here, 'n' (number analysed) is defined as subjects analysed at specified categories. Data for this endpoint was not planned to be collected and analysed for placebo arm.
|
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End point type |
Secondary
|
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End point timeframe |
Predose, 1.5 hours and 4 hours post-dose on Week 0 (Day 1), Weeks 1 (Day 8), 2 (Day 15), 4 (Day 29), and 6 (Day 43)
|
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| Notes [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Descriptive statistics for this endpoint were planned to be analysed for specified arm only as the other arm was the placebo. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||
|
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End point title |
Change from Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Score - Ability to Participate in Social Roles and Activities (APS) T-Scores | ||||||||||||||||||||||||||||||
End point description |
Change from baseline in PROMIS score - ability to participate in social roles and activities T-Scores were reported. The PROMIS - APS item bank assesses the perceived ability to perform one’s usual social roles and activities. The item bank did not use a time frame (for example, over the past seven days) when assessing the APS. The Short Form 4a included 4 items that represent this concept. Each question had 5 response options ranging in value from 1 to 5 with higher scores indicating better social function. Total raw score for short form was calculated by summing the values of the response to each question, so for the 4-item form, the lowest possible raw score was 4; the highest possible raw score was 20. The total raw score was converted to a T score with a mean of 50 and a standard deviation of 10. FAS was used. Here, 'n' (number analysed) is defined as subjects analysed at specified categories.
|
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End point type |
Secondary
|
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End point timeframe |
Baseline (Day 1), Weeks 1, 2, 3, 4, 5, and 6
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
|
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End point title |
Change from Baseline in Generalized Anxiety Disorder 7 (GAD-7) Total Score | |||||||||||||||||||||
End point description |
Change from baseline in GAD-7 total score were reported. GAD-7 is a brief and validated 7-item self-reported questionnaire for assessment of overall GAD. Subjects responded 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, with a higher score representing a more severe condition. Item responses were summed to yield GAD-7 total score which ranged of 0 to 21, where higher scores indicated more anxiety. FAS included all randomised subjects who received at least 1 dose of study intervention and had both the baseline and at least 1 postbaseline MADRS measurement. Here, 'n' (number analysed) is defined as subjects analysed at specified categories.
|
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End point type |
Secondary
|
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End point timeframe |
Baseline (Day 1), Weeks 2, 4, and 6
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Change from Baseline in Patient Health Questionnaire-9 (PHQ-9) Total Score | ||||||||||||||||||||||||||||||
End point description |
Change from baseline in PHQ-9 total score were reported. PHQ-9 is 9-item, self-report scale assessed depressive symptoms. Each item was rated on 4-point scale (0=Not at all, 1=several days, 2=more than half days, 3=nearly every day. The subject's item responses were summed to provide PHQ-9 total score (range of 0 to 27) with higher scores indicating greater severity of depressive symptoms. FAS included all randomised subjects who received at least 1 dose of study intervention and had both the baseline and at least 1 postbaseline MADRS measurement. Here, 'N' (subjects analysed) signifies number of subjects evaluable for this endpoint. Here, 'n' (number analysed) is defined as subjects analysed at specified categories.
|
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End point type |
Secondary
|
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End point timeframe |
Baseline (Day 1), Weeks 1, 2, 3, 4, 5, and 6
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
|
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End point title |
Change from Baseline in MADRS Total Score up to Week 6 (Subgroup of Subjects with Messenger Ribonucleic Acid [mRNA] Transcript Levels) | ||||||||||||
End point description |
Subgroup included subjects with mRNA transcript levels (exceeded medium level for both P2RX7 and IL-1-beta). MADRS was clinician-rated scale designed to measure depression severity and detect changes due to AD treatment. MADRS evaluated reported sadness, apparent sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Scale consist 10 items, each was scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms); higher score indicated more severe condition. MADRS total score was sum of scores from individual question items; ranged: 0-60; higher scores indicated more severe conditions. Negative change in MADRS total score indicated improvement. FAS was used. 99999 refer to mean and standard deviation (SD) were not calculable because planned analysis was terminated as reliable data could not be produced using single step polymerase chain reaction method.
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End point type |
Secondary
|
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End point timeframe |
From Baseline (Day 1) up to Week 6
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|
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from Baseline in MADRS Total Score up to Week 6 (Concomitant Medication Subgroup Analysis) | ||||||||||||||||||||||||
End point description |
Concomitant medication subgroup analysis included subjects with BD not taking any mood stabilizer or antipsychotic, taking a mood stabilizer alone, taking antipsychotic alone, and taking a combination of mood stabilizer and an antipsychotic. MADRS measures depression severity, detects changes due to AD treatment. It consists of 10 items (evaluate apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, suicidal thoughts), scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), summed for a total possible score of 0 to 60. Higher scores indicate more severe conditions. Negative change in score indicates improvement. FAS was used for the analysis. 99999 refer to standard deviation not estimable for single subject and 99999 at n=0 signifies no subject was available for the analysis.
|
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End point type |
Secondary
|
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End point timeframe |
From Baseline (Day 1) up to Week 6
|
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| No statistical analyses for this end point | |||||||||||||||||||||||||
|
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End point title |
Number of Subjects Who Achieved Response at Week 6 | |||||||||
End point description |
Number of subjects who achieved response at Week 6 were reported. Response was defined as greater than or equal to (>=)50% improvement in MADRS total score from baseline. MADRS was a clinician-rated scale designed to measure depression severity and detect changes due to AD treatment. The MADRS evaluated reported sadness, apparent sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. The scale consist of 10 items each of which was scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms),with higher score indicating a more severe condition. The MADRS total score was the sum of scores from individual question items and it ranged from 0 to 60, with higher scores indicated more severe conditions. Negative change in MADRS total score indicated improvement. FAS was used.
|
|||||||||
End point type |
Secondary
|
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End point timeframe |
Week 6
|
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|
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| No statistical analyses for this end point | ||||||||||
|
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End point title |
Number of Subjects Who Achieved Remission at Week 6 | |||||||||
End point description |
Number of subjects who achieved remission at Week 6 were reported. Remission was defined as MADRS total score <=12. MADRS was a clinician-rated scale designed to measure depression severity and detect changes due to AD treatment. The MADRS evaluated reported sadness, apparent sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. The scale consist of 10 items each of which was scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms),with higher score indicating a more severe condition. The MADRS total score was the sum of scores from individual question items and it ranged from 0 to 60, with higher scores indicated more severe conditions. Negative change in MADRS total score indicated improvement. FAS was used.
|
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End point type |
Secondary
|
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End point timeframe |
Week 6
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|
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| No statistical analyses for this end point | ||||||||||
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Adverse events information
|
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Timeframe for reporting adverse events |
All-cause mortality: From screening (-28 days) up to end of study (up to 12 weeks); SAEs and Other AEs: From Day 1 (Week 0) up to 30 days after the last dose (up to 11 weeks)
|
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Adverse event reporting additional description |
All-cause mortality was analysed on all randomized subjects in the study. SAEs and Other AEs were analysed on safety analysis set that included all randomised subjects who took at least 1 dose of study intervention.
|
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
26.1
|
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Reporting groups
|
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Reporting group title |
Placebo
|
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Reporting group description |
During DB treatment phase, subjects received placebo capsule (matching to JNJ-55308942), orally once daily from Day 1 (Week 0) up to 6 weeks. Subjects were then followed up for up to 2 weeks after their last dose (up to Day 56). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
JNJ-55308942
|
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Reporting group description |
During double-blind (DB) treatment phase, subjects received JNJ-55308942 capsule, orally once daily from Day 1 (Week 0) up to 6 weeks. Subjects were then followed up for up to 2 weeks after their last dose (up to Day 56). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
01 Feb 2022 |
The rational for this amendment was to remove the safety, tolerability, and efficacy preview (STEP) interview, Patient-Reported Outcomes Measurement Information System (PROMIS) - social isolation and Patient and Global Impression of Severity for Depression(PGI-S), to add clarification on the antidepressant treatment history-short form (ATHF-SF), to replace the DARS with the Snaith-Hamilton Pleasure Scale (SHAPS), to replace the SMDDS with the Patient Health Questionnaire (PHQ-9), and the use of the AiCure application, to add the digital health assessment by the AiCure app, and to add the urine drug screen (UDS) to every visit. |
||
04 Jul 2022 |
The rational for this amendment was to add clarifications on timing of self-rating assessments, downloading of apps, prohibited concomitant therapy. To add recommendations on order of events and when the second pharmacogenomics sample could be taken. To add Canada as a new country where TruCulture sampling would be performed, provided flexibility on the country list where TruCulture assay or determination of peripheral blood mononuclear cells (PBMCs) inflammatory profiles could be performed and to remove Russia where we were provisioning phones to all subjects. |
||
27 Jul 2022 |
The rational for this amendment was to change the definition of a treatment-emergent adverse events (TEAE) on regulatory request. |
||
25 Jan 2023 |
The rational for this amendment was to allow for operational efficiency the prescreening visit would be removed from the study and the prescreening assessment, a blood sample for P2RX7 genotyping, would be part of the screening phase. |
||
18 Aug 2023 |
The rational for this amendment was Antipsychotics approved for bipolar depression (BD), however not effective for treating the current major depressive episode, whether taken alone or in combination with a mood stabilizer might be permitted. AiCure services for medication compliance and meal intake were discontinued and replaced with Q1.6 for medication reminders. Vendor names were removed from the body of the protocol. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
