An Open-Label Trial of Tocilizumab in Schizophrenia

• Status: Completed
• Trial end date: 2014-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This study is a Phase 1 clinical trail 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 (Ig) gamma-1 subclass. Tocilizumab is formulated as a concentrate for solution for infusion, and will be administered by intravenous infusion.

The investigators propose an 8-week trial to determine the safety, tolerability, and effectiveness of tocilizumab, given in addition to antipsychotic medications, in 10 stable outpatients with schizophrenia. The investigators hypothesize that tocilizumab will be associated with clinically significant improvement in cognition and total psychotic symptoms over the course of the trial. Tocilizumab is administered as an intravenous infusion every 4 weeks. Following a screening evaluation, participants will receive two infusions of tocilizumab, one at baseline and another at week 4 of the study. The investigators will measure changes in cognitive function and symptoms over an 8-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.

Data presented in 2008 showed the effectiveness of tocilizumab in combination therapy with methotrexate for rheumatoid arthritis treatment. In further studies, it was effective and generally well tolerated when administered either as monotherapy or in combination with conventional disease-modifying antirheumatic drugs in adult patients with moderate to severe rheumatoid arthritis.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Brian Miller

Criteria

Inclusion Criteria:

• male and female

• age 18-50

• capable of giving informed consent

• diagnosis of schizophrenia

• stable based on clinical judgement, no psychiatric hospitalizations in past 3 months, and on the same psychotropic medications for >4 weeks

• taking a non-clozapine antipsychotic

Exclusion Criteria:

• imminent danger to self/others

• antibiotic use in the past 2 weeks

• current scheduled use of immunomodulatory agents

• history of an immune disorder

• illicit drug use in the past 30 days

• any unstable or untreated medical condition

• history of gastrointestinal ulcers, diverticulitis, malignancy, central nervous system demyelinating disorder, seizure disorder, or tuberculosis

• low absolute neutrophil (<2000) or platelet (<100,000) count

• abnormal hepatic (AST or ALT >1.5 times the upper limit of normal) or renal (BUN or creatinine>1.5 times the upper limit of normal) function

• any abnormal lab test result judged to be clinically significant

• active, chronic or recurrent infections

• pregnancy

• breastfeeding

• female and of child-bearing potential who is not using any contraception