Siltuximab in Schizophrenia

NCT02796859 | Unknown Phase 1 DMC

• 1 other identifier: 15T-005
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a Phase 1 clinical trial to determine the safety, tolerability, and efficacy of Siltuximab (Sylvant) as an adjunct to antipsychotic medications in stable outpatients with schizophrenia. Siltuximab (structural formula C6450H9932N1688O2016S50) is a recombinant chimeric (human-murine) anti-human interleukin-6 (IL-6) monoclonal antibody. Siltuximab is formulated as a concentrate for solution for infusion, and will be administered by intravenous infusion. The investigators propose a 9-week randomized controlled trial of siltuximab, given in adjunct to antipsychotics, in N=30 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 siltuximab will be associated with significant improvement in cognition compared to placebo in patients with schizophrenia, baseline IL-6 levels are higher in siltuximab-treated responders versus non-responders, and there will be greater decreases in hsCRP from baseline to week 6 in siltuximab-treated versus placebo-treated responders, with response defined as ≥0.5 SD improvement in cognition. Siltuximab is administered as an intravenous infusion every 3 weeks. Following a screening evaluation, participants will receive three infusions of siltuximab, one at baseline, another at week 3 of the study, and another at week 6. The investigators will measure changes in cognitive function and symptoms over a 9-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. Janssen Pharmaceuticals, Inc. began the clinical development of siltuximab for the treatment of multicentric Castleman's disease, a rare blood disorder. Other clinical studies with siltuximab have been conduced for patients with B-cell non-Hodgkin's lymphoma, multiple myeloma, and ovarian cancer. In April 2014,siltuxiumab was approved by the U.S. Food and Drug Administration (US FDA) as Sylvant for human immunodeficiency virus (HIV)-negative and human herpesvirus-8 (HHV-8)-negative multicentric Castleman's disease.

Conditions

Schizophrenia; Psychotic Disorders

Keywords

Inflammation; Psychosis; Schizophrenia

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 will be calculated as the BACS composite score at 9 weeks minus the BACS composite score at baseline.

  Baseline and 9 weeks

Secondary Outcomes (1)

• Change in Total Psychotic Symptoms

  Baseline and 9 weeks

Study Arms (2)

Treatment Group

ACTIVE COMPARATOR

Subjects in the siltuximab group will receive an 11 mg/kg infusion at baseline, and weeks 3 and 6, as per the recommended dosing for multicentric Castleman's disease

Drug: Siltuximab

Control Group

PLACEBO COMPARATOR

Subjects in the placebo group will receive an infusion of normal saline (with the same packaging and volume as the siltuximab group) at baseline, and weeks 3 and 6.

Drug: normal saline

Interventions

Siltuximab DRUG

Investigational agent

Also known as: Sylvant

Treatment Group

normal saline DRUG

Placebo

Also known as: 0.9% NS

Control Group

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• capable of giving informed consent
• diagnosis of schizophrenia or schizoaffective disorder
• stable based on clinical judgment
• taking a non-clozapine antipsychotic
• on the same psychotropic medications for \>4 weeks
• hsCRP \>0.3 mg/dL at the screening visit

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, CNS demyelinating disorder, seizure disorder, or exposure to tuberculosis
• low absolute neutrophil (\<2000) or platelet (\<100,000) count
• abnormal hepatic function (AST or ALT \>1.5 times the upper limit of normal) or renal function (BUN or creatinine \>1.5 times the upper limit of normal)
• any abnormal lab test result judged to be clinically significant
• active or chronic infections
• pregnancy, breast feeding, or female of child-bearing potential who is not using any contraception.

Sponsors & Collaborators

• Brian Miller: lead
• Stanley Medical Research Institute: collaborator

Study Sites (1)

Augusta University

Augusta, Georgia, 30912, United States

RECRUITING

Related Publications (34)

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MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders; Inflammation

Interventions

siltuximab; Saline Solution

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Central Study Contacts

Brian J Miller, MD

CONTACT

706-721-4445; brmiller@augusta.edu

Rebecca Nichols, MBA

CONTACT

706-721-4605; rnichols@augusta.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 26, 2016
• First Posted: June 13, 2016
• Study Start: May 1, 2016
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: July 21, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share

Locations

US (1)