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

Study Description

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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

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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

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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

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Primary Outcome Measures :

1. Change From Baseline in Hamilton Depression Rating Scale (HDRS17) Total Score at Week 12 [ Time Frame: Baseline upto Week 12 ]
   The HDRS17 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. It is the most widely used symptom severity measure for depression. Each of the 17 items is rated by the clinician on either a 3- or a 5-point scale. The higher the score, the more severe the depression.

Secondary Outcome Measures :

1. Change From Baseline in Snaith Hamilton Pleasure Scale (SHAPS) Total Score at Week 12 [ Time Frame: Baseline and Week 12 ]
   Anhedonia, the inability to experience pleasure, is a core symptom of depression. The Snaith-Hamilton Pleasure Scale (SHAPS) is a short, 14-item instrument to measure anhedonia, which has been shown to be valid and reliable in normal and clinical samples. Each of the 14 items has a set of four response categories: Definitely Agree (= 1), Agree (= 2), Disagree (= 3), and Definitely Disagree (= 4). A higher total score indicates higher levels of state anhedonia.
2. Change From Baseline in Clinical Global Impression - Severity (CGI-S) Total Score at Week 12 [ Time Frame: Baseline and Week 12 ]
   The CGI-S provides an overall clinician-determined summary measure that takes into account all available information, including knowledge of the participant's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the participant's ability to function. The CGI evaluates the severity of psychopathology from 1 to 7. Higher score indicates more severity.
3. Change From Baseline in Patient Health Questionnaire (PHQ-9) at Week 12 [ Time Frame: Baseline and Week 12 ]
   The PHQ-9 is used as a participant-reported measure of depressive symptomatology. The PHQ-9 is a 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), with a total score range of 0 to 27. The recall period is 2 weeks. High score indicates higher symptoms.
4. Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) at Week 12 [ Time Frame: Baseline and Week 12 ]
   The FACIT-Fatigue is a questionnaire that assesses self-reported tiredness, weakness, and difficulty conducting usual activities due to fatigue. The total FACIT-Fatigue score ranges from 0 to 52, with a higher score indicating less fatigue.
5. Number of Participants as Remitters [ Time Frame: Week 12 ]
   Remitters are defined as participants with HDRS17 total score <= 7 at 12 week.
6. Number of Participants as Responders [ Time Frame: Baseline and Week 12 ]
   Participants with >= 50 percent (%) improvement on the HDRS17 total score from baseline at Week 12.
7. Number of Participants with Adverse Events (AEs) and Serious AEs [ Time Frame: Screening up to End of Follow-up Phase (approximately up to 32 - 35 weeks) ]
   An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
8. The change from baseline to endpoint on the Hamilton Depression Rating Scale (HDRS17) total score [ Time Frame: Baseline upto Week 12 ]
   The HDRS17 is a clinician-administered rating scale designed to assess the severity of symptoms in patients diagnosed with depression with a score range of 0 to 52. Questions are related to symptoms such as depressed mood, guilt feelings, suicide, sleep disturbances, anxiety levels and weight loss.The higher the score, the more severe the depression.

Eligibility Criteria

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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

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Sponsors and Collaborators

Janssen Research & Development, LLC

Investigators

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

More Information

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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
Last Update Posted:	September 21, 2018
Last Verified:	September 2018

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