Neutralizing Interleukin (IL)-6

NCT07493317 | Recruiting Phase 2 FDA Drug

• 1 other identifier: STUDY-25-01000
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The proposed study aims to establish the feasibility and safety of subcutaneous tocilizumab, a monoclonal antibody (mAb) against interleukin (IL)-6 receptor, in adults with Major Depressive Disorder (MDD) and evidence of peripheral immune activation. IL-6 is a pro-inflammatory cytokine implicated in the pathophysiology of depression. The investigators hypothesize that neutralizing peripheral immune signaling via IL-6 receptor blockade with tocilizumab will improve neural and behavioral measures of reward processing. This is an open-label, proof-of concept, trial in which up to N=20 adults with MDD meeting a specific immune enrichment criterion will receive open-label tocilizumab over 8 weeks. A healthy control (HC) group (N=20) will undergo baseline neuroimaging and blood-based biomarker assessment without receiving the study drug to aid interpretation of findings. Blood-based immune markers and brain MRI scans (including task-based reward activation and resting-state functional connectivity) will be assessed at baseline for all participants and again post treatment for the MDD group.

Conditions

Major Depressive Disorder

Keywords

Depression; Monoclonal antibody; Healthy Volunteer; Tocilizumab; Interleukin-6; Anhedonia; fMRI

Outcome Measures

Primary Outcomes (1)

• Change in ventral stratal activation during reward processing (fMRI)

  Change in ventral stratal activation (brain response) during reward processing (fMRI)

  at week 0 and week 10

Secondary Outcomes (3)

• Change in Snaith-Hamilton Pleasure Scale (SHAPS)

  at week 0 and week 12

• Change in Montgomery-Asberg Depression Rating Scale (MADRS)

  at week 0 and week 12

• Change in Temporal Experience of Pleasure Scale (TEPS)

  at week 0 and week 12

Study Arms (2)

Participants with MDD

EXPERIMENTAL

MDD participants will receive 5 doses of tocilizumab 162 mg administered via subcutaneous injection every 2 weeks over an 8-week period.

Drug: Tocilizumab

Healthy Control

NO INTERVENTION

Healthy controls will serve as a baseline comparison group for neuroimaging and biomarker analyses only.

Interventions

Tocilizumab DRUG

One treatment condition in an open-label study design: subcutaneous injection of tocilizumab 162 mg at weeks 0, 2, 4, 6, and 8.

Participants with MDD

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For MDD participants:
• Written informed consent;
• Ability to comply with the requirements of the study as determined by the PI;
• Ages 18-70 years;
• Any gender;
• DSM-5 diagnosis of MDD in a current Major Depressive Episode;
• Immune enrichment criterion: elevated monocyte count ≥ 500 cells/μL at screening;
• If patient is on antidepressant medication, they must be on a stable dose for ≥4 weeks prior to treatment;
• SHAPS score ≥20
• If female of childbearing potential, must agree to use of a medically accepted form of contraception, or else agree to abstinence until 6 months after the last dose of study drug;
• Male patients, if heterosexually active with a partner who is female of childbearing potential, pregnant, or breastfeeding, must agree to barrier contraception for the treatment period and for at least 6 months after the last dose of the study drug. Female partners of male participants must use at least one form of highly effective contraception starting at least one cycle prior to male patient study drug initiation until 6 months after the last dose of study drug.
• Meet all MRI safety criteria.
• For Healthy Volunteers:
• Written informed consent;
• Ability to comply with the requirements of the study as determined by the PI;

You may not qualify if:

• For MDD Participants
• A primary DSM-5 psychiatric diagnosis other than MDD, with the exception of comorbid anxiety disorders (including agoraphobia, generalized anxiety disorder, social anxiety disorder, panic disorder) and post-traumatic stress disorder, which are permitted.
• History of schizophrenia, schizoaffective disorder, other psychotic disorder, MDD with psychotic features, or bipolar I or II disorder.
• Diagnosis of a major neurocognitive disorder.
• Moderate or severe substance use disorder within the past 6 months (excluding nicotine use disorder).
• Positive urine toxicology screen for illicit substances at screening.
• Serious or imminent risk of self-harm or violence, as determined by the PI, including:
• Suicide attempt within the past 2 years, or
• C-SSRS ideation score \>2 within the past month.
• Any contraindication to MRI, including claustrophobia, retained metallic foreign bodies, magnetic implants or pacemakers, or inability to tolerate MRI procedures.
• Clinically significant abnormalities on physical examination or laboratory testing.
• Unstable or clinically significant medical illness, including but not limited to hepatic, renal, gastrointestinal, respiratory, cardiovascular (including ischemic heart disease), endocrine, neurologic (including history of severe head injury), immunologic, or hematologic conditions.
• Evidence of active or untreated infection, including
• Active tuberculosis (TB) or untreated latent TB
• Positive QuantiFERON-TB Gold test at screening

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major; Depression; Anhedonia

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• James Murrough

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alexia Lizzano

CONTACT

3322437059; alexia.lizzano@mssm.edu

Mackenzie Hargrove

CONTACT

3322437052; mackenzie.brown@mssm.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 20, 2026
• First Posted: March 25, 2026
• Study Start: March 26, 2026
• Primary Completion (Estimated): February 6, 2031
• Study Completion (Estimated): February 6, 2031
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)