Tocilizumab in Schizophrenia

Summary

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.

Conditions

• Schizophrenia
• Psychotic Disorders

Interventions

DRUG

Tocilizumab

Investigational agent

DRUG

Normal saline

Placebo

Sponsors & Collaborators

• Brain & Behavior Research Foundation

  collaborator OTHER

• Brian Miller

  lead OTHER

Principal Investigators

• Brian J Miller, MD · Augusta University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

55 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-09-30

Primary Completion

2023-12-31

Completion

2023-12-31

Countries

• United States

Study Locations