An Open-Label Trial of Tocilizumab in Schizophrenia

NCT01696929 | Completed Phase 1 Results FDA Drug

• 1 other identifier: Pro00000405
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Schizophrenia

Keywords

tocilizumab; safety; tolerability; efficacy; schizophrenia; improvement; cognition; psychotic symptoms; baseline IL-6 levels

Outcome Measures

Primary Outcomes (1)

• Change in Cognition

  The Brief Assessment of Cognition in Schizophrenia (BACS) is the metric used to characterize cognition in this study. The BACS consists of 6 subscales: Verbal Memory (range 0-75), Working Memory (range 0-28), Motor Speed (range 0-100), Verbal Fluency (measure is total number of words generated in two 60 second trials), Attention and Processing speed (range 0-110), and Executive Function (range 0-22). For each subscale, higher scores reflect better cognition. For each subscale, a Standard Deviation Score was calculated based on normative data (Keefe et al. Norms and standardization of the Brief Assessment of Cognition in Schizophrenia (BACS). Schizophrenia Research 102 (2008) 108-115). The BACS composite score is calculated as the average Standard Deviation Score of the 6 subscale scores. The change in BACS composite score was calculated as the BACS composite score at 8 weeks minus the BACS composite score at baseline.

  Change in BACS composite score from baseline to 8 weeks

Secondary Outcomes (1)

• Change in Total Psychotic Symptoms

  Change in PANSS total score from baseline to 8 weeks

Study Arms (1)

Tocilizumab

EXPERIMENTAL

Following a screening evaluation, participants will receive two infusions of tocilizumab, one at baseline and another at week 4 of the study. All subjects will receive a 4 mg/kg infusion of tocilizumab, the recommended starting dose for adults with rheumatoid arthritis.

Drug: Tocilizumab

Interventions

Tocilizumab DRUG

Therapeutic/Pharmacologic Class of Drug: Tocilizumab is a recombinant humanized anti-human interleukin-6 (IL-6) receptor monoclonal antibody of the immunoglobulin (Ig) gamma-1 subclass. Type of Dosage Form: Concentrate for solution for infusion. Route of Administration: Intravenous (i.v.) infusion.

Also known as: Brand Name: Actemra, NDA/Serial Number: STN 125276/S022 (Cross ref: IND 11972)

Tocilizumab

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Brian Miller: lead

Study Sites (1)

Georgia Health Sciences University

Augusta, Georgia, 30912, United States

Location

Related Publications (16)

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• Muller N, Riedel M, Schwarz MJ, Engel RR. Clinical effects of COX-2 inhibitors on cognition in schizophrenia. Eur Arch Psychiatry Clin Neurosci. 2005 Apr;255(2):149-51. doi: 10.1007/s00406-004-0548-4. Epub 2004 Nov 19.

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MeSH Terms

Conditions

Schizophrenia

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Results Point of Contact

• Title: Dr. Brian Miller
• Organization: Georgia Regents University

brmiller@gru.edu

706-721-4445

Study Officials

• Brian Miller, MD, PhD, MPH

  Augusta University - Department of Psychiatry and Health Behavior

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: September 24, 2012
• First Posted: October 2, 2012
• Study Start: September 1, 2012
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: July 29, 2021
• Results First Posted: October 7, 2015

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)