Tocilizumab as Add-On Treatment For Residual Positive, Negative, and Cognitive Symptoms of Schizophrenia
Condition: Schizophrenia; Schizoaffective Disorder
MeSH terms: Neurobehavioral Manifestations; Schizophrenia; Psychotic Disorders
Intervention: Tocilizumab; Placebo
Intervention description: 8mg/kg intravenously via iv drip over 60 min; intravenously via iv drip over 60 min
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 59.0
Sex: All
Minimum age: 18 Years
Maximum age: 59 Years
Healthy volunteers: No

Summary:

      Randomized, double-blind clinical trial of tocilizumab vs. placebo as add-on treatment for
      residual positive, negative, and cognitive symptoms in schizophrenia. The primary study
      hypothesis is that individuals receiving tocilizumab will show greater improvements in their
      PANSS total scores than those taking placebo.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Fulfill DSM-IV criteria for schizophrenic illness, schizoaffective disorder

          -  Negative urine toxicology

          -  Capacity to understand the study and give written informed consent

          -  Must be on a stable dose of antipsychotic medications, up to two medications, except
             for clozapine, for at least 4 weeks if oral or 2 cycles if depot. Mood stabilizers,
             benzodiazepines and antidepressants are allowed as long as no change for 4 weeks.

          -  Moderate level of symptomatology

        Exclusion Criteria:

          -  Pregnancy or lactation, lack of effective birth control during the 15 days before the
             initial day of the study and for the duration of the drug trial

          -  Unstable medical or neurological condition (including chronic rashes other than mild
             eczema, ANC < 2000, platelet count < 120,000, severe liver disease or AST/ALT greater
             than 1.5 times the ULN at baseline, or any chronic inflammatory or immunologic
             disorder that impairs the immune system, a current severe infection, intestinal
             diverticula, or tuberculosis (latent or active-patients with a positive ppd but
             negative chest x ray may participate) or a live vaccine within one month of receiving
             study drug

          -  Any current non medicinal use of amphetamines, opiates, cocaine, sedative-hypnotics,
             cannabis, or other psychoactive drugs (other than nicotine)

          -  Currently taking a medication known to cause neutropenia (clozapine, carbamazepine),
             or another disease modifying anti-rheumatic drugs (DMARD)

          -  Any history of substance dependence (other than nicotine or cannabis) within the
             previous 6 months or a history of substance abuse within the previous 1 month (other
             than nicotine)

          -  Impaired intellectual functioning

          -  Major surgery (including joint surgery) within 8 weeks prior to screening or planned
             major surgery within 6 months following randomization

          -  Treatment with any investigational agent within 4 weeks (or 5 half-lives of the
             investigational drug, whichever is longer)

          -  Previous treatment with any cell-depleting therapies, including investigational agents
             or approved therapies, some examples are CAMPATH, anti-CD4, anti-CD5, anti-CD3,
             anti-CD19 and anti-CD20

          -  Treatment with intravenous gamma globulin, plasmapheresis or Prosorba column within 6
             months of baseline

          -  Previous treatment with tocilizumab (an exception to this criterion may be granted for
             single dose exposure upon application to the sponsor on case-by-case basis

          -  Any previous treatment with alkylating agents such as chlorambucil, or with a total
             lymphoid irradiation

          -  History of severe allergic or anaphylactic reactions to human, humanized or murine
             monoclonal antibodies

          -  Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary
             (including obstructive pulmonary disease), renal, hepatic, endocrine (include
             uncontrolled diabetes mellitus) or gastrointestinal disease (including complicated
             diverticulitis, ulcerative colitis, or Crohn's disease)

          -  Current liver disease

          -  Known active current or history of recurrent bacterial, viral, fungal, mycobacterial
             or other infections (including but not limited to tuberculosis and atypical
             mycobacterial disease, Hepatitis B and C, and herpes zoster, but excluding fungal
             infections of nail beds).

          -  Any major episode of infection requiring hospitalization or treatment with IV
             antibiotics within 4 weeks or oral antibiotics within 2 weeks

          -  Active TB requiring treatment within the previous 3 years.

          -  Primary or secondary immunodeficiency (history of or currently active)

          -  Evidence of active malignant disease, malignancies diagnosed within the previous 10
             years (including hematological malignancies and solid tumors, except basal and
             squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that has
             been excised and cured) or breast cancer diagnosed within the previous 20 years

          -  Neuropathies or other conditions that might interfere with pain evaluation unless
             related to primary disease under investigation

          -  Lack of peripheral venous access

          -  Body weight of >150 kg

          -  Serum creatinine > 1/6mg/dL (141 umol/L) in female patients and > 1.9 mg/dL (168
             umol/L) in male patients. Patients with serum creatinine values exceeding limits may
             be eligible for the study if their estimated glomerular filtration rates (GFR) are >
             30

          -  Total Bilirubin >ULN

          -  Hemoglobin < 85g/L

          -  White Blood Cells <3.0 x 10^9/L

          -  Absolute Lymphocyte Count < 0.5 x 10^9/L

          -  Positive Hepatitis BsAg or Hepatitis C antibody

        Additional Exclusion Criteria for MRI portion

          -  Metal implants or a history of metal working

          -  Lifetime diagnosis of asthma with asthmatic symptoms within the past 3 years

          -  Lifetime diagnosis of renal failure or renal disease

          -  Lifetime diagnosis of hypertension or diabetes

          -  Renal insufficiency

          -  More than one previous gadolinium scan