This study is a Phase 1 clinical trial to determine the safety, tolerability, and efficacy of
Siltuximab (Sylvant) as an adjunct to antipsychotic medications in stable outpatients with
schizophrenia. Siltuximab (structural formula C6450H9932N1688O2016S50) is a recombinant
chimeric (human-murine) anti-human interleukin-6 (IL-6) monoclonal antibody. Siltuximab is
formulated as a concentrate for solution for infusion, and will be administered by
intravenous infusion.
The investigators propose a 9-week randomized controlled trial of siltuximab, given in
adjunct to antipsychotics, in N=30 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 siltuximab will be associated with significant improvement in cognition
compared to placebo in patients with schizophrenia, baseline IL-6 levels are higher in
siltuximab-treated responders versus non-responders, and there will be greater decreases in
hsCRP from baseline to week 6 in siltuximab-treated versus placebo-treated responders, with
response defined as ≥0.5 SD improvement in cognition. Siltuximab is administered as an
intravenous infusion every 3 weeks. Following a screening evaluation, participants will
receive three infusions of siltuximab, one at baseline, another at week 3 of the study, and
another at week 6. The investigators will measure changes in cognitive function and symptoms
over a 9-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. Janssen Pharmaceuticals, Inc. began the clinical
development of siltuximab for the treatment of multicentric Castleman's disease, a rare blood
disorder. Other clinical studies with siltuximab have been conduced for patients with B-cell
non-Hodgkin's lymphoma, multiple myeloma, and ovarian cancer.
In April 2014,siltuxiumab was approved by the U.S. Food and Drug Administration (US FDA) as
Sylvant for human immunodeficiency virus (HIV)-negative and human herpesvirus-8
(HHV-8)-negative multicentric Castleman's disease.