12-Week Study Evaluating the Efficacy, Safety, and Tolerability of Adjunctive Infliximab for Bipolar I/II Depression

Inclusion criteria

• Fifth edition of Diagnostic and Statistical Manual for Mental Disorders (DSM-5) criteria for major depressive episode as part of bipolar I/II disorder and are able to provide written informed consent
• HAMD-17 score >= 20
• Young Mania Rating Scale score < 12
• Previous failed trial (i.e., inefficacy) of quetiapine and one other Canadian Network for Mood and Anxiety Treatments (CANMAT) BD guideline/FDA approved first line treatment for the depressive phase of BD during the index episode and/or during a prior episode
• Currently prescribed conventional mood stabilizer or atypical antipsychotic agent
• Received conventional treatment for bipolar depression for a minimum of 4 weeks prior to randomization
• Females of childbearing potential must test negative for pregnancy and must be using adequate birth control measures throughout the study and must continue such precautions for 6 months after receiving the last study drug administration.

Participants will also need to meet one of the following inflammatory indicators:

• Central Obesity (ethnicity-specific waist circumference - see table below for specific values) OR BMI ≥30 kg/m2.

AND

• Raised triglycerides: ≥1.7 mmol/L (150 mg/dL) or specific treatment for this lipid abnormality OR
• Reduced HDL-cholesterol: <1.03 mmol/L (40 mg/dL) in males; <1.29 mmol/L (50 mg/dL) in females or specific treatment for this lipid abnormality OR
• Raised Blood Pressure: Raised blood pressure Systolic: ≥130 mm Hg or diastolic: ≥85 mm Hg or treatment of previously diagnosed hypertension.
• Diabetes: 8-hour fasting plasma glucose ≥ 7.0 mmol/L or Hb-A1C test ≥ 6.5% (as per the 2013 CDA diagnostic criteria) or previously diagnosed type 1 or 2 diabetes (current prescription medication for diabetes acceptable of diagnosis). Participants with child onset of diabetes will be excluded.
• Inflammatory bowel disorder (Ulcerative Colitis, Crohn's disease).
• Rheumatological disorders (rheumatoid arthiristis); Psoriasis.
• Smoking cigarettes (daily - minimum of ½ pack).
• High sensitivity C-reactive protein level of ≥5 mg/L via blood test at screening

Exclusion criteria

• Another concurrent psychiatric disorder that requires primary clinical attention
• History of schizophrenia
• Active psychotic symptoms
• Substance abuse and/or dependence within past 6 months
• Electroconvulsive therapy in the past 6 months
• Actively suicidal or evaluated as being a suicide risk [HAMD-17 suicide item >= 3 or Montogomery Asberg Depression Rating Scale (MADRS) suicide item >= 4, or according to clinical judgement using the C-SSRS]
• Clinically significant unstable medical illness
• Severe infections such as sepsis, abscess, tuberculosis and opportunistic infections
• Viral hepatitis B
• History of Hepatitis C ( documented or suspected)
• Any autoimmune disorder
• History of tuberculosis or a high risk of tuberculosis exposure
• Human Immunodeficiency Virus confirmed by laboratory testing
• Active fungal infection
• History of recurrent viral or bacterial infections
• Received within 3 months prior to screening or are expected to receive any live viral vaccine or live bacterial vaccinations during the trial or up to 3 months after the last administration of study agent
• C. difficile infection within the past 4 months
• History of lymphoproliferative disease
• History of cancer, excluding basal cell or squamous cell carcinoma of the skin (fully excised with no recurrence)
• Unstable cardiovascular, endocrinological, hematological, hepatic, renal or neurological disease determined by physical examination and laboratory testing
• Concomitant diagnosis or any history of congestive heart failure
• Concomitant treatment with non-steroidal and steroidal anti-inflammatory medications or other biologics
• Current or past exposure to anti-TNF biologics
• Previous immediate hypersensitivity response, including anaphylaxis to an immunoglobulin product (plasma-derived or recombinant, e.g. monoclonal antibody)
• Known allergies, hypersensitivity or intolerance to infliximab or its excipients
• Known allergy to murine proteins or other chimeric proteins
• Currently on or have used any investigational drug within 30 days prior to screening, or within 5 half-lives of the investigational agent
• Females who are pregnant or breastfeeding