This study is a Phase 1 clinical trial to determine the safety, tolerability, and efficacy of
Tocilizumab (Actemra) as an adjunct to antipsychotic medications in stable outpatients with
schizophrenia. Tocilizumab (structural formula C6428H9976N1720O2018S42) is a recombinant
humanized anti-human interleukin-6 (IL-6) receptor monoclonal antibody of the immunoglobulin
G1 (IgG1) subclass. Tocilizumab is formulated as a concentrate for solution for infusion, and
will be administered by intravenous infusion.
The investigators propose a 12-week randomized controlled trial of tocilizumab, given in
adjunct to antipsychotics, in N=20 stable outpatients with schizophrenia or schizoaffective
disorder and evidence of increased inflammation in the peripheral blood (high-sensitivity
C-reactive protein [hsCRP]>0.5 mg/dL). The investigators hypothesize that adjunctive
treatment with tocilizumab will be associated with significant improvement in cognition
compared to placebo in patients with schizophrenia, and baseline IL-6 levels are higher in
tocilizumab-treated responders versus non-responders, and there will be greater decreases in
hsCRP from baseline to week 12 in tocilizumab-versus placebo-treated responders, with
response defined as ≥0.5 standard deviation (SD) improvement in cognition. Tocilizumab is
administered as an intravenous infusion every 4 weeks. Following a screening evaluation,
participants will receive three infusions of siltuximab, one at baseline, another at week 4
of the study, and another at week 8. The investigators will measure changes in cognitive
function and symptoms over a 12-week period. Complementing previous positive clinical trials
of non-steroidal anti-inflammatory drugs, this would be a "proof-of-concept" study that
targeting specific cytokines is a viable treatment for schizophrenia.
Interleukin 6 and its receptor were discovered and cloned at Osaka University, Japan, by
Tadamitsu Kishimoto in the 1980s. In 1997, Chugai Pharmaceuticals began the clinical
development of tocilizumab for the treatment of rheumatoid arthritis. Clinical studies for
Castleman's disease and systemic juvenile idiopathic arthritis started in 2001 and 2002,
respectively. Hoffmann-La Roche co-developed the drug due to a license agreement in 2003.
On 11 January 2010, Tocilizumab was approved by the U.S. Food and Drug Administration (US
FDA) as Actemra for the treatment of rheumatoid arthritis. The FDA approved tocilizumab for
the treatment of systemic juvenile idiopathic arthritis for children from two years of age in
April 2011.