Back to resultsAn Efficacy and Safety Study of Sirukumab in Participants With Major Depressive Disorder
Primary Purpose
Depressive Disorder, Major
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Sirukumab 50 mg
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Depressive Disorder, Major focused on measuring Depressive disorder, major, Sirukumab
Eligibility Criteria
Inclusion Criteria:
- Participants must have a primary DSM-5 diagnosis of MDD
- Must have a HDRS total score greater than or equal to (>=) 18 at screening and predose at Day 1, as recorded by the remote independent rater and must not demonstrate an improvement of > 25 percent (%) on their HDRS total score from the screening to baseline visit
- Must be medically stable on the basis of physical examination, medical history, vital signs, clinical laboratory tests and 12-lead ECG performed at screening. If there are abnormalities, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant. This determination must be recorded in the subject's source documents and initialed by the investigator
- Participants with hypothyroidism who are on stable treatment for 3 months prior to screening are required to have thyroid stimulating hormone (TSH) and free thyroxine (FT4) obtained. If the TSH value is out of range, but FT4 is normal, such cases should be discussed directly with the medical monitor before the subject is enrolled. If the FT4 value is out of range, the participant is not eligible
Exclusion Criteria:
- Any other current Axis one psychiatric condition, including, but not limited to, MDD with current psychotic features, bipolar disorder (including lifetime diagnosis), obsessive-compulsive disorder, borderline personality disorder, eating disorder (eg, bulimia, anorexia nervosa), or schizophrenia (lifetime). The MINI will be used to screen for comorbid psychiatric diagnoses. As noted above, subjects with a diagnosis of comorbid GAD, Post-Traumatic Stress Disorder, Persistent Depressive Disorder, ADHD, Social Anxiety Disorder, Panic Disorder with or without agoraphobia or Nicotine/Caffeine Dependence may be included, if the investigator considers MDD to be the primary diagnosis
- A history of alcohol or substance use disorder (abuse/dependence) within 6 months prior to screening (nicotine and caffeine dependence are not exclusionary)
- A current or recent (within the past year) history of clinically significant suicidal ideation (corresponding to a score of >= 3 for ideation) or any suicidal behavior within the past year, as validated on the C-SSRS at screening or baseline. Subjects with a prior suicide attempt of any sort, or history of prior serious suicidal ideation/plan should be carefully screened for current suicidal ideation and only included at the discretion of the investigator
- More than 3 failed antidepressant treatments (of adequate dose and duration) in the current episode of depression (verified by the MGH-ATRQ)
- Length of current major depressive episode > 60 months
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Sirukumab 50 milligram (mg)
Placebo
Arm Description
Participants will receive sirukumab 50 mg as subcutaneous injection on Day 1, 28 and 56.
Participants will receive matching placebo on Day 1, 28 and 56.
Outcomes
Primary Outcome Measures
Change From Baseline in Hamilton Depression Rating Scale (HDRS-17) Total Score at Week 12
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 (0 to 52) was calculated by adding the scores of all 17 items. For each item as well as the total score, a higher score represents a more severe condition. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Secondary Outcome Measures
Change From Baseline in HDRS-17 Total Score at Weeks 1, 4 and 8
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 (0 to 52) was calculated by adding the scores of all 17 items. For each item as well as the total score, a higher score represents a more severe condition.
Percentage of Participants With Remission as Assessed by HDRS-17 Total Score at Week 12
Remission- Percentage of participants with HDRS-17 total score less than or equal to (<=) 7 were considered as remitters. HDRS-17 defined as clinician-administered rating scale designed to assess severity of symptoms in participants diagnosed with depression with score range of 0 to 52. Each of 17 items is rated by 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 (0 to 52) was calculated by adding scores of all 17 items. For each item as well as total score, a higher score represents a more severe condition.
Percentage of Participants With Response as Assessed by HDRS-17 Total Score at Week 12
Response- Percentage of participants with greater than or equal to (>=) 50 percent (%) improvement on the HDRS-17 total score from baseline at Week 12 were considered as responders. The HDRS-17 defined as 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 (0 to 52) was calculated by adding the scores of all 17 items. For each item as well as the total score, a higher score represents a more severe condition.
Change From Baseline in Clinical Global Impression - Severity (CGI-S) Total Score at Weeks 1, 4, 8, 12, 16, and 22
CGI-S defined as clinician-rated scale that assesses the severity of mental illness on a scale of 0 to 7. Considering total clinical experience, a participant was assessed on severity of mental illness at the time of rating according to: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 patients. A higher score implies a more severe condition.
Change From Baseline in Patient Health Questionnaire (PHQ-9) Total Score at Weeks 1, 4, 8, 12, 16, and 22
The PHQ-9 used as a participant-reported measure of depressive symptomatology. The PHQ-9 is 9-item scale, where 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 participant's item responses were summed to provide a total score range of 0 to 27. Higher scores indicates greater severity of depressive symptoms. The recall period is 2 weeks.
Change From Baseline in Snaith Hamilton Pleasure Scale (SHAPS) Total Score (Definition 1) at Weeks 1, 4, 8, 12, 16, and 22
The Snaith-Hamilton Pleasure Scale (SHAPS) is short, 14-item instrument to measure anhedonia. Each of the 14 items has a set of four response categories (Definition 1): Definitely Agree (=1), Agree (= 2), Disagree (= 3), and Definitely Disagree (= 4). A SHAPS total score was calculated as the sum of the 14 item scores with a total score range from 14 to 56. A higher total score indicates higher levels of state anhedonia.
Change From Baseline in Snaith Hamilton Pleasure Scale (SHAPS) Total Score (Definition 2) at Weeks 1, 4, 8, 12, 16, and 22
The Snaith-Hamilton Pleasure Scale (SHAPS) is short, 14-item instrument to measure anhedonia. Each of the 14 items has a set of four response categories (Definition 2): Definitely Agree (= 0), Agree (= 0), Disagree (= 1), and Definitely Disagree (= 1). A SHAPS total score was calculated as the sum of the 14 item scores with a score range from 0 to 14. A higher total score indicates higher levels of state anhedonia.
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score at Weeks 1, 4, 8, 12, 16, and 22
The FACIT-Fatigue is a questionnaire that assesses self-reported tiredness, weakness, and difficulty conducting usual activities due to fatigue. The subscale consists 13-item instrument to measure fatigue. Each of the 13 items has a set of five response categories: Not at all (=0), A little bit (=1), Somewhat (=2), Quite a bit (=3) and Very much (=4). A total FACIT-Fatigue subscale score was calculated as the sum of the 13 item scores (reserved scores [4 - score] for all except for 2 items: "I have energy" and "I am able to do my usual activities"), and ranges from 0 to 52, with a higher score indicating less fatigue.
Full Information
NCT ID
NCT02473289
First Posted
June 12, 2015
Last Updated
May 21, 2019
Sponsor
Janssen Research & Development, LLC
1. Study Identification
Unique Protocol Identification Number
NCT02473289
Brief Title
An Efficacy and Safety Study of Sirukumab in Participants With Major Depressive Disorder
Official Title
A Double-Blind, Placebo-Controlled, Multicenter Study of Sirukumab as Adjunctive Treatment to a Monoaminergic Antidepressant in Adults With Major Depressive Disorder
Study Type
Interventional
2. Study Status
Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
July 23, 2015 (Actual)
Primary Completion Date
May 22, 2018 (Actual)
Study Completion Date
May 22, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC
4. Oversight
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate the efficacy of sirukumab as adjunctive treatment to antidepressant therapy (monoaminergic antidepressant) where sirukumab (administered as a 50 milligram (mg) subcutaneous (SC) injection at Day 1, Day 28 and Day 56 during the 12- week double-blind treatment period) is compared to adjunctive placebo based on the change from baseline to 12-week endpoint in depressive symptoms as measured by the total score on the Hamilton Depression Rating Scale (HDRS), in participants diagnosed with Major Depressive Disorder (MDD) who have had a suboptimal response to the current standard oral antidepressant therapy and have a screening high sensitivity C-Reactive Protein (hsCRP) >=0.300 milligram per deciliters (mg/dL) (International System of Units (SI) 3.00 mg/L). A cohort of subjects with hsCRP <0.300 milligram per deciliter will also be enrolled to allow a better understanding of the relationship between CRP and clinical changes.
Detailed Description
A double-blind, placebo-controlled, multicenter study of sirukumab as adjunctive treatment to a monoaminergic antidepressant in adults with major depressive disorder. Participants will be randomly assigned to receive either placebo or sirukumab 50 milligram (mg) at a ratio of 1:1 at Day 1, 28 and 56. Participants will primarily be assessed for change from baseline in Hamilton Depression Rating Scale (HDRS17) score at Week 12. Safety will be monitored throughout the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Depressive Disorder, Major
Keywords
Depressive disorder, major, Sirukumab
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
193 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sirukumab 50 milligram (mg)
Arm Type
Experimental
Arm Description
Participants will receive sirukumab 50 mg as subcutaneous injection on Day 1, 28 and 56.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will receive matching placebo on Day 1, 28 and 56.
Intervention Type
Drug
Intervention Name(s)
Sirukumab 50 mg
Intervention Description
Participants will receive sirukumab 50 mg as subcutaneous injection on Day 1, 28 and 56.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Participants will receive matching placebo on Day 1, 28 and 56.
Primary Outcome Measure Information:
Title
Change From Baseline in Hamilton Depression Rating Scale (HDRS-17) Total Score at Week 12
Description
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 (0 to 52) was calculated by adding the scores of all 17 items. For each item as well as the total score, a higher score represents a more severe condition. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Time Frame
Baseline and Week 12
Secondary Outcome Measure Information:
Title
Change From Baseline in HDRS-17 Total Score at Weeks 1, 4 and 8
Description
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 (0 to 52) was calculated by adding the scores of all 17 items. For each item as well as the total score, a higher score represents a more severe condition.
Time Frame
Baseline, Weeks 1, 4 and 8
Title
Percentage of Participants With Remission as Assessed by HDRS-17 Total Score at Week 12
Description
Remission- Percentage of participants with HDRS-17 total score less than or equal to (<=) 7 were considered as remitters. HDRS-17 defined as clinician-administered rating scale designed to assess severity of symptoms in participants diagnosed with depression with score range of 0 to 52. Each of 17 items is rated by 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 (0 to 52) was calculated by adding scores of all 17 items. For each item as well as total score, a higher score represents a more severe condition.
Time Frame
Week 12
Title
Percentage of Participants With Response as Assessed by HDRS-17 Total Score at Week 12
Description
Response- Percentage of participants with greater than or equal to (>=) 50 percent (%) improvement on the HDRS-17 total score from baseline at Week 12 were considered as responders. The HDRS-17 defined as 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 (0 to 52) was calculated by adding the scores of all 17 items. For each item as well as the total score, a higher score represents a more severe condition.
Time Frame
Week 12
Title
Change From Baseline in Clinical Global Impression - Severity (CGI-S) Total Score at Weeks 1, 4, 8, 12, 16, and 22
Description
CGI-S defined as clinician-rated scale that assesses the severity of mental illness on a scale of 0 to 7. Considering total clinical experience, a participant was assessed on severity of mental illness at the time of rating according to: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 patients. A higher score implies a more severe condition.
Time Frame
Baseline and Weeks 1, 4, 8, 12, 16, and 22
Title
Change From Baseline in Patient Health Questionnaire (PHQ-9) Total Score at Weeks 1, 4, 8, 12, 16, and 22
Description
The PHQ-9 used as a participant-reported measure of depressive symptomatology. The PHQ-9 is 9-item scale, where 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 participant's item responses were summed to provide a total score range of 0 to 27. Higher scores indicates greater severity of depressive symptoms. The recall period is 2 weeks.
Time Frame
Baseline and Weeks 1, 4, 8, 12, 16, and 22
Title
Change From Baseline in Snaith Hamilton Pleasure Scale (SHAPS) Total Score (Definition 1) at Weeks 1, 4, 8, 12, 16, and 22
Description
The Snaith-Hamilton Pleasure Scale (SHAPS) is short, 14-item instrument to measure anhedonia. Each of the 14 items has a set of four response categories (Definition 1): Definitely Agree (=1), Agree (= 2), Disagree (= 3), and Definitely Disagree (= 4). A SHAPS total score was calculated as the sum of the 14 item scores with a total score range from 14 to 56. A higher total score indicates higher levels of state anhedonia.
Time Frame
Baseline and Weeks 1, 4, 8, 12, 16, and 22
Title
Change From Baseline in Snaith Hamilton Pleasure Scale (SHAPS) Total Score (Definition 2) at Weeks 1, 4, 8, 12, 16, and 22
Description
The Snaith-Hamilton Pleasure Scale (SHAPS) is short, 14-item instrument to measure anhedonia. Each of the 14 items has a set of four response categories (Definition 2): Definitely Agree (= 0), Agree (= 0), Disagree (= 1), and Definitely Disagree (= 1). A SHAPS total score was calculated as the sum of the 14 item scores with a score range from 0 to 14. A higher total score indicates higher levels of state anhedonia.
Time Frame
Baseline and Weeks 1, 4, 8, 12, 16, and 22
Title
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score at Weeks 1, 4, 8, 12, 16, and 22
Description
The FACIT-Fatigue is a questionnaire that assesses self-reported tiredness, weakness, and difficulty conducting usual activities due to fatigue. The subscale consists 13-item instrument to measure fatigue. Each of the 13 items has a set of five response categories: Not at all (=0), A little bit (=1), Somewhat (=2), Quite a bit (=3) and Very much (=4). A total FACIT-Fatigue subscale score was calculated as the sum of the 13 item scores (reserved scores [4 - score] for all except for 2 items: "I have energy" and "I am able to do my usual activities"), and ranges from 0 to 52, with a higher score indicating less fatigue.
Time Frame
Baseline and Weeks 1, 4, 8, 12, 16, and 22
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participants must have a primary DSM-5 diagnosis of MDD
Must have a HDRS total score greater than or equal to (>=) 18 at screening and predose at Day 1, as recorded by the remote independent rater and must not demonstrate an improvement of > 25 percent (%) on their HDRS total score from the screening to baseline visit
Must be medically stable on the basis of physical examination, medical history, vital signs, clinical laboratory tests and 12-lead ECG performed at screening. If there are abnormalities, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant. This determination must be recorded in the subject's source documents and initialed by the investigator
Participants with hypothyroidism who are on stable treatment for 3 months prior to screening are required to have thyroid stimulating hormone (TSH) and free thyroxine (FT4) obtained. If the TSH value is out of range, but FT4 is normal, such cases should be discussed directly with the medical monitor before the subject is enrolled. If the FT4 value is out of range, the participant is not eligible
Exclusion Criteria:
Any other current Axis one psychiatric condition, including, but not limited to, MDD with current psychotic features, bipolar disorder (including lifetime diagnosis), obsessive-compulsive disorder, borderline personality disorder, eating disorder (eg, bulimia, anorexia nervosa), or schizophrenia (lifetime). The MINI will be used to screen for comorbid psychiatric diagnoses. As noted above, subjects with a diagnosis of comorbid GAD, Post-Traumatic Stress Disorder, Persistent Depressive Disorder, ADHD, Social Anxiety Disorder, Panic Disorder with or without agoraphobia or Nicotine/Caffeine Dependence may be included, if the investigator considers MDD to be the primary diagnosis
A history of alcohol or substance use disorder (abuse/dependence) within 6 months prior to screening (nicotine and caffeine dependence are not exclusionary)
A current or recent (within the past year) history of clinically significant suicidal ideation (corresponding to a score of >= 3 for ideation) or any suicidal behavior within the past year, as validated on the C-SSRS at screening or baseline. Subjects with a prior suicide attempt of any sort, or history of prior serious suicidal ideation/plan should be carefully screened for current suicidal ideation and only included at the discretion of the investigator
More than 3 failed antidepressant treatments (of adequate dose and duration) in the current episode of depression (verified by the MGH-ATRQ)
Length of current major depressive episode > 60 months
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
City
Birmingham
State/Province
Alabama
Country
United States
City
Little Rock
State/Province
Arkansas
Country
United States
City
Bellflower
State/Province
California
Country
United States
City
Glendale
State/Province
California
Country
United States
City
Lemon Grove
State/Province
California
Country
United States
City
Orange
State/Province
California
Country
United States
City
Santa Ana
State/Province
California
Country
United States
City
Torrance
State/Province
California
Country
United States
City
Wildomar
State/Province
California
Country
United States
City
Atlanta
State/Province
Georgia
Country
United States
City
Decatur
State/Province
Georgia
Country
United States
City
Chicago
State/Province
Illinois
Country
United States
City
Edgewood
State/Province
Kentucky
Country
United States
City
Baltimore
State/Province
Maryland
Country
United States
City
Grand Rapids
State/Province
Michigan
Country
United States
City
Lebanon
State/Province
New Hampshire
Country
United States
City
Brooklyn
State/Province
New York
Country
United States
City
New York
State/Province
New York
Country
United States
City
Staten Island
State/Province
New York
Country
United States
City
Columbus
State/Province
Ohio
Country
United States
City
Oklahoma City
State/Province
Oklahoma
Country
United States
City
Houston
State/Province
Texas
Country
United States
City
Plano
State/Province
Texas
Country
United States
City
Salt Lake City
State/Province
Utah
Country
United States
City
Edmonton
State/Province
Alberta
Country
Canada
City
Chatham
State/Province
Ontario
Country
Canada
City
Hamilton
State/Province
Ontario
Country
Canada
City
Toronto
State/Province
Ontario
Country
Canada
City
Belchatow
Country
Poland
City
Bydgoszcz
Country
Poland
City
Chelmno
Country
Poland
City
Gorlice
Country
Poland
City
Lublin
Country
Poland
City
Karelia
Country
Russian Federation
City
Moscow
Country
Russian Federation
City
Nizny Novgorod
Country
Russian Federation
City
Rostov-on-Don
Country
Russian Federation
City
Saratov Region
Country
Russian Federation
City
Saratov
Country
Russian Federation
City
St-Petersburg
Country
Russian Federation
City
Tomsk
Country
Russian Federation
City
Yaroslavl
Country
Russian Federation
City
Edinburgh
Country
United Kingdom
City
Glasgow
Country
United Kingdom
City
Oxford
Country
United Kingdom
City
Redruth
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
An Efficacy and Safety Study of Sirukumab in Participants With Major Depressive Disorder
We'll reach out to this number within 24 hrs