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

NCT07615075 | Not Yet Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: HP-00118919
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Schizophrenia; Schizo Affective Disorder; Healthy

Outcome Measures

Primary Outcomes (1)

• 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) 1. Mild impairment 2. Moderate impairment 3. Moderately severe impairment 4. Severe deficit or impairment. Higher total scores indicate a greater severity of negative symptoms

  16 weeks

Study Arms (2)

Placebo Comparator: Placebo

PLACEBO COMPARATOR

Drug: Placebo

IL-23

ACTIVE COMPARATOR

Drug: IL-23

Interventions

Placebo DRUG

Placebo control

Placebo Comparator: Placebo

IL-23 DRUG

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).

IL-23

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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)
• 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

Sponsors & Collaborators

• University of Maryland, Baltimore: lead

Study Sites (1)

Maryland Psychiatric Research Center (MPRC) Outpatient Research Program (ORP); the MPRC Treatment Research Program (TRP)

Catonsville, Maryland, 21228, United States

Location

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

Interleukin-23

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Deanna L Kelly, PharmD, BCPP

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ann Kearns, MS

CONTACT

410-402-6854; akearns@som.umaryland.edu

Mathew Glassman, MA

CONTACT

410-402-6411; mglassman@som.umaryland.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Maryland Psychiatric Research Center

Study Record Dates

• First Submitted: May 14, 2026
• First Posted: May 29, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2030
• Last Updated: May 29, 2026

Record last verified: 2026-05

Locations

US (1)