Clinical Trial of an IL-23 Inhibitor for Immune Activation in Clinical Trial of an IL-23 Inhibitor for Immune Activation in People With Schizophrenia

Randomized Double-Blind Clinical Trial of an IL-23 Inhibitor for Immune Activation in People With Schizophrenia

This 16 week clinical trial investigates a precision-medicine approach to schizophrenia by targeting a biologically distinct subgroup,-approximately one-third of patients-characterized by the presence of anti-gliadin antibodies (AGA IgG+) which is associated with elevated inflammation in the IL-23/IL-17 immune axis (Th17 pathway). This specific biotype is associated with pronounced negative symptoms, cognitive deficits, and reduced white matter integrity. Building on evidence that this pathway can be modulated to improve clinical outcomes, we are conducting a randomized, double-blind clinical trial of mirikizumab, an FDA-approved monoclonal antibody targeting IL-23, in addition to current antipsychotics, in schizophrenia patients who are positive for AGA IgG.

The primary objective is to determine whether mirikizumab - a repurposed FDA approved monoclonal antibody treatment inhibiting IL-23-- will be superior to placebo in treating experiential (e.g., anhedonia and asociality) negative symptoms and cognitive impairments. Secondary aims will be to assess changes in T-cell subtypes and relative abundance by gene expression, peripheral cytokines, and neuroimaging markers (in a smaller subset). By focusing on this patient subgroup, who are identified by their immune status, the research aims to provide a targeted, revolutionary treatment for symptoms that have traditionally remained resistant to standard antipsychotic therapies.

This protocol includes a screening phase, with a separate consent form which is intended to identify those with AGA IgG antibodies. This screening portion will also serve to compare other aspects of immune functioning and the TH17 pathway between patient groups and controls in order to further characterize and show that Th17 (and similar immune cell lines) are different between AGA IgG positive, AGA IgG negative and healthy controls of either status.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy; Schizophrenia; Schizo Affective Disorder
• Intervention / Treatment: Drug: Placebo; Drug: IL-23

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ann Kearns, MS; Phone Number: 410-402-6854; Email: akearns@som.umaryland.edu
• Study Contact Backup: Name: Mathew Glassman, MA; Phone Number: 410-402-6411; Email: mglassman@som.umaryland.edu

Study Locations

• United States
  • Maryland
    • Catonsville, Maryland, United States, 21228
      • Maryland Psychiatric Research Center (MPRC) Outpatient Research Program (ORP); the MPRC Treatment Research Program (TRP)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria: Screening

• Age range of 18-64
• Schizophrenia Group: Meet meet DSM 5 criteria for schizophrenia or schizoaffective disorder
• Healthy Control Group: Does NOT meet DSM 5 criteria for schizophrenia or schizoaffective disorder, bipolar disorder, or major depressive disorder.

Exclusion Criteria: Screening

• Known current active infection, or taking an immunosuppressive medications (e.g. oral scheduled corticosteroids, chemotherapy or transplantation or HIV/AIDs associated drugs), or the scheduled use of anti-inflammatory medications, including NSAIDs (e.g. ibuprofen, celecoxib, or naproxen) or aspirin > 81 mg on a daily basis will be excluded.
• Score of less than 10/12 on the ESC

Inclusion Criteria: Clinical Trial

• Age range of 18-64
• Meet meet DSM 5 criteria for schizophrenia or schizoaffective disorder
• Personal and Social Performance (PSP) Scale score of ≤70.
• Treated with the same antipsychotic for at least 30 days and having received a constant therapeutic dose for at least 15 days prior to study entry
• One test in the past of elevated AGA IgG antibodies (AGA IgG > 15)

Exclusion Criteria: Clinical Trial

• Current infection, including HIV, and Hepatitis C (blood draw) or tuberculosis (TB*); or an organic brain disorder or medical condition, whose pathology or treatment could alter the presentation or treatment of schizophrenia or significantly increase the risk associated with the proposed treatment protocol.
• Currently taking immunosuppressive medications (e.g. oral scheduled corticosteroids, chemotherapy or transplantation or HIV/AIDs associated drugs); or the scheduled use of anti-inflammatory medications, including NSAIDs (e.g. ibuprofen, celecoxib, or naproxen) or aspirin > 81 mg on a daily basis will be excluded. The use of PRN anti-inflammatory agents will be allowed
• Score of less than 10/12 on the ESC

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Comparator: Placebo	Drug: Placebo; Placebo control
Active Comparator: IL-23	Drug: IL-23; IL-23 induction dosage at initiation, week 4 and week 8 treatments consisting of 300 mg intravenously (IV) over at least 30 minutes, and one maintenance dose at week 12 consisting of 200 mg subcutaneously (given as either one injection of 200 mg or as two consecutive injections of 100 mg each).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in negative symptoms in schizophrenia	Change in negative symptoms in schizophrenia, specific experiential negative symptoms (i.e., motivation and pleasure) using The Clinical Assessment Interview for Negative Symptoms (CAINS) is a clinician-rated tool developed to assess the negative symptoms of schizophrenia, aligning with the NIMH's consensus on negative symptom domains. It comprises two main subscales: the Motivation and Pleasure (MAP) scale and the Expression (EXP) scale. The CAINS-MAP subscale specifically evaluates deficits in motivation, social engagement, and hedonic experience across social, vocational, and recreational contexts. The 0-4 Scoring System:0: No impairment (within the range of normal variation); Mild impairment; Moderate impairment; Moderately severe impairment; Severe deficit or impairment. Higher total scores indicate a greater severity of negative symptoms	16 weeks

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Investigators: Principal Investigator: Deanna L Kelly, PharmD, BCPP, University of Maryland, Baltimore

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2030

Study Registration Dates

• First Submitted: May 14, 2026
• First Submitted That Met QC Criteria: May 22, 2026
• First Posted (Actual): May 29, 2026

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 22, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Schizophrenia; Psychotic Disorders; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Intercellular Signaling Peptides and Proteins; Cytokines; Interleukins; Interleukin-23
• Other Study ID Numbers: HP-00118919

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No