Siltuximab in Schizophrenia

• Status: Recruiting
• Trial end date: 2023-12-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Brian Miller
• Collaborator: Stanley Medical Research Institute
• Treatments: Antibodies, Monoclonal; Siltuximab

Criteria

Inclusion Criteria:

• 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

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, 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.