Tocilizumab as Add-On Treatment For Residual Positive, Negative, and Cognitive Symptoms of Schizophrenia

NCT02034474 | Completed Phase 4 Results

• 1 other identifier: 6729
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

Randomized, double-blind clinical trial of tocilizumab vs. placebo as add-on treatment for residual positive, negative, and cognitive symptoms in schizophrenia. The primary study hypothesis is that individuals receiving tocilizumab will show greater improvements in their PANSS total scores than those taking placebo.

Conditions

Schizophrenia; Schizoaffective Disorder

Outcome Measures

Primary Outcomes (1)

• Clinical Response to Tocilizumab

  To evaluate an anticipated clinical response to tocilizumab treatment including positive, negative and cognitive symptoms by the change in the Positive and Negative Syndrome Scale (PANSS) total score. Score ranges from 30 to 210 for PANSS total, 16-112 for General, 7-49 for positive and 7-49 for negative symptoms subscales. A lower score means less symptomatic. There is a total score and general psychopathology scores, a positive symptoms score and a negative symptom score. The unit of measure is units on a scale from 1-7, whole numbers only. Summed scores are simply added to each other

  Baseline (start of tocilizumab) through 12 weeks. We present the change scores

Secondary Outcomes (2)

• Cognitive Symptomatology - Overall MATRICS t Score Change

  Baseline (start of tocilizumab) through 12 weeks

• Cognitive Symptomatology - UPSA-B Score Change

  Baseline (start of tocilizumab) through 12 weeks

Other Outcomes (1)

• Relationship Between Baseline IL-6 Levels and Positive, Negative and Cognitive Symptoms and Impairment

  Baseline (start of tocilizumab) through 12 weeks

Study Arms (2)

tocilizumab

EXPERIMENTAL

Tocilizumab will be administered at day 0, week 4 and week 8 via an iv drip over 60 min. Dose is 8mg/kg but may be reduced to 4mg/kg if intolerable. Maximum dose will be 800mg.

Drug: Tocilizumab

Placebo

PLACEBO COMPARATOR

Placebo will be administered intravenously via an iv drip over 60 min

Drug: Placebo

Interventions

Tocilizumab DRUG

8mg/kg intravenously via iv drip over 60 min

Also known as: Actemra

tocilizumab

Placebo DRUG

intravenously via iv drip over 60 min

Also known as: Saline Drip

Placebo

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Fulfill DSM-IV criteria for schizophrenic illness, schizoaffective disorder
• Negative urine toxicology
• Capacity to understand the study and give written informed consent
• Must be on a stable dose of antipsychotic medications, up to two medications, except for clozapine, for at least 4 weeks if oral or 2 cycles if depot. Mood stabilizers, benzodiazepines and antidepressants are allowed as long as no change for 4 weeks.
• Moderate level of symptomatology

You may not qualify if:

• Pregnancy or lactation, lack of effective birth control during the 15 days before the initial day of the study and for the duration of the drug trial
• Unstable medical or neurological condition (including chronic rashes other than mild eczema, ANC \< 2000, platelet count \< 120,000, severe liver disease or AST/ALT greater than 1.5 times the ULN at baseline, or any chronic inflammatory or immunologic disorder that impairs the immune system, a current severe infection, intestinal diverticula, or tuberculosis (latent or active-patients with a positive ppd but negative chest x ray may participate) or a live vaccine within one month of receiving study drug
• Any current non medicinal use of amphetamines, opiates, cocaine, sedative-hypnotics, cannabis, or other psychoactive drugs (other than nicotine)
• Currently taking a medication known to cause neutropenia (clozapine, carbamazepine), or another disease modifying anti-rheumatic drugs (DMARD)
• Any history of substance dependence (other than nicotine or cannabis) within the previous 6 months or a history of substance abuse within the previous 1 month (other than nicotine)
• Impaired intellectual functioning
• Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization
• Treatment with any investigational agent within 4 weeks (or 5 half-lives of the investigational drug, whichever is longer)
• Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies, some examples are CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19 and anti-CD20
• Treatment with intravenous gamma globulin, plasmapheresis or Prosorba column within 6 months of baseline
• Previous treatment with tocilizumab (an exception to this criterion may be granted for single dose exposure upon application to the sponsor on case-by-case basis
• Any previous treatment with alkylating agents such as chlorambucil, or with a total lymphoid irradiation
• History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies
• Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (include uncontrolled diabetes mellitus) or gastrointestinal disease (including complicated diverticulitis, ulcerative colitis, or Crohn's disease)
• Current liver disease

Sponsors & Collaborators

• New York State Psychiatric Institute: lead
• Stanley Medical Research Institute: collaborator

Study Sites (1)

New York State Psychiatric Institute

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Results Point of Contact

• Title: Ragy Girgis,MD
• Organization: NYSPI

ragy.girgis@nyspi.columbia.edu

6467745553

Study Officials

• Ragy R Girgis, MD

  New York State Psychiatric Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Psychiatry at CUMC

Study Record Dates

• First Submitted: January 9, 2014
• First Posted: January 13, 2014
• Study Start: February 1, 2014
• Primary Completion: February 6, 2017
• Study Completion: February 6, 2017
• Last Updated: December 26, 2018
• Results First Posted: December 26, 2018

Record last verified: 2018-12

Locations

US (1)