An Efficacy and Safety Study of Sirukumab in Participants With Major Depressive Disorder

• ClinicalTrials.gov Identifier: NCT02473289
• Recruitment Status: Completed
• First Posted: June 16, 2015
• Results First Posted: June 11, 2019
• Last Update Posted: June 11, 2019
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

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.

Condition or disease	Intervention/treatment	Phase
Depressive Disorder, Major	Drug: Sirukumab 50 mg; Drug: Placebo	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 193 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Double-Blind, Placebo-Controlled, Multicenter Study of Sirukumab as Adjunctive Treatment to a Monoaminergic Antidepressant in Adults With Major Depressive Disorder
• Actual Study Start Date: July 23, 2015
• Actual Primary Completion Date: May 22, 2018
• Actual Study Completion Date: May 22, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Sirukumab 50 milligram (mg); Participants will receive sirukumab 50 mg as subcutaneous injection on Day 1, 28 and 56.	Drug: Sirukumab 50 mg; Participants will receive sirukumab 50 mg as subcutaneous injection on Day 1, 28 and 56.
Placebo Comparator: Placebo; Participants will receive matching placebo on Day 1, 28 and 56.	Drug: Placebo; Participants will receive matching placebo on Day 1, 28 and 56.

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in Hamilton Depression Rating Scale (HDRS-17) Total Score at Week 12 [ Time Frame: Baseline and 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 :

1. Change From Baseline in HDRS-17 Total Score at Weeks 1, 4 and 8 [ Time Frame: Baseline, 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.
2. Percentage of Participants With Remission as Assessed by HDRS-17 Total Score at Week 12 [ Time Frame: 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.
3. Percentage of Participants With Response as Assessed by HDRS-17 Total Score at Week 12 [ Time Frame: 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.
4. Change From Baseline in Clinical Global Impression - Severity (CGI-S) Total Score at Weeks 1, 4, 8, 12, 16, and 22 [ Time Frame: Baseline and 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.
5. Change From Baseline in Patient Health Questionnaire (PHQ-9) Total Score at Weeks 1, 4, 8, 12, 16, and 22 [ Time Frame: Baseline and 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.
6. Change From Baseline in Snaith Hamilton Pleasure Scale (SHAPS) Total Score (Definition 1) at Weeks 1, 4, 8, 12, 16, and 22 [ Time Frame: Baseline and 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.
7. Change From Baseline in Snaith Hamilton Pleasure Scale (SHAPS) Total Score (Definition 2) at Weeks 1, 4, 8, 12, 16, and 22 [ Time Frame: Baseline and 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.
8. Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score at Weeks 1, 4, 8, 12, 16, and 22 [ Time Frame: Baseline and 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.

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 64 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

  Show 46 Study Locations

Sponsors and Collaborators

Janssen Research & Development, LLC

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial; Janssen Research & Development, LLC

  Study Documents (Full-Text)

Documents provided by Janssen Research & Development, LLC:

Study Protocol  [PDF] January 22, 2018

Statistical Analysis Plan  [PDF] December 3, 2018

More Information

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT02473289 History of Changes
• Other Study ID Numbers: CR107171; CNTO136MDD2001 ( Other Identifier: Janssen Research & Development, LLC ); 2014-005206-37 ( EudraCT Number )
• First Posted: June 16, 2015
• Results First Posted: June 11, 2019
• Last Update Posted: June 11, 2019
• Last Verified: May 2019

• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Janssen Research & Development, LLC:

Depressive disorder, major; Sirukumab

Additional relevant MeSH terms:

Disease; Depressive Disorder; Depression; Depressive Disorder, Major; Pathologic Processes; Mood Disorders; Mental Disorders; Behavioral Symptoms; Antibodies, Monoclonal; Immunologic Factors; Physiological Effects of Drugs