An Open-Label Trial of Tocilizumab in Schizophrenia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Brian Miller, Georgia Regents University
ClinicalTrials.gov Identifier:
NCT01696929
First received: September 24, 2012
Last updated: June 23, 2016
Last verified: June 2016
  Purpose

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.


Condition Intervention Phase
Schizophrenia
Drug: Tocilizumab
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label Trial of Tocilizumab in Schizophrenia

Resource links provided by NLM:


Further study details as provided by Augusta University:

Primary Outcome Measures:
  • Change in Cognition [ Time Frame: Change in BACS composite score from baseline to 8 weeks ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change in Total Psychotic Symptoms [ Time Frame: Change in PANSS total score from baseline to 8 weeks ] [ Designated as safety issue: No ]
    The Positive and Negative Symptoms Scale (PANSS) is the metric used to characterize psychotic symptoms in this study. The PANSS consists of 30 items, each scored 1-7. The range for the PANSS total score is 30-210. There are 3 subscales - PANSS positive score (range 7-49), PANSS negative score (range 7-49), and PANSS general score (range 16-112). PANSS total score is the summation of these 3 subscales. Higher values for the total and subscale scores reflect more severe psychopathology. A positive change in PANSS total score reflects an increase in psychopathology. A negative change in PANSS total score reflects a decrease in psychopathology.


Enrollment: 8
Study Start Date: September 2012
Study Completion Date: December 2014
Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tocilizumab
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

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.

Other Names:
  • Brand Name: Actemra
  • NDA/Serial Number: STN 125276/S022 (Cross ref: IND 11972)

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01696929

Locations
United States, Georgia
Georgia Health Sciences University
Augusta, Georgia, United States, 30912
Sponsors and Collaborators
Brian Miller
Investigators
Principal Investigator: Brian Miller, MD, PhD, MPH Georgia Health Sciences University Department of Psychiatry and Health Behavior
  More Information

Publications:

Responsible Party: Brian Miller, Assistant Professor, Georgia Regents University
ClinicalTrials.gov Identifier: NCT01696929     History of Changes
Other Study ID Numbers: Pro00000405 
Study First Received: September 24, 2012
Results First Received: August 5, 2015
Last Updated: June 23, 2016
Health Authority: United States: Institutional Review Board

Keywords provided by Augusta University:
tocilizumab
safety
tolerability
efficacy
schizophrenia
improvement
cognition
psychotic symptoms
baseline IL-6 levels

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders

ClinicalTrials.gov processed this record on August 23, 2016