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

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.

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