An Efficacy and Safety Study of Sirukumab in Participants With Major Depressive Disorder
Condition: Depressive Disorder, Major
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Intervention: Sirukumab 50 mg; Placebo
Intervention 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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 193.0
Sex: All
Minimum age: 21 Years
Maximum age: 64 Years
Healthy volunteers: No
Keywords: Depressive disorder, major; Sirukumab

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.
    

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