Recruiting
Phase 2

Tocilizumab

Sponsor:

Icahn School of Medicine at Mount Sinai

Code:

NCT07493317

Conditions

Major Depressive Disorder

Eligibility Criteria

Sex: All

Age: 18 - 70

Healthy Volunteers: Accepted

Interventions

Tocilizumab

Study Details

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

Study ID

NCT07493317

Start date

Mar 26, 2026

Status verified date

Apr, 2026

Completion date

Feb 6, 2031

Anticipated

Primary completion date

Feb 6, 2031

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70

Healthy Volunteers: Accepted

Inclusion Criteria:

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;
  • Ages 18-70
  • Any gender;
  • No current or past DSM-5 psychiatric disorder;
  • Meet all MRI safety criteria.

Exclusion Criteria:

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
  • Known HIV infection
  • Active Hepatitis B or Hepatitis C infection
  • Current or recent (within an appropriate washout period) use of biologic therapies or other immunosuppressive agents (PRN NSAIDs permitted).
  • Known hypersensitivity to tocilizumab or its excipients.
  • Receipt of a live or live-attenuated vaccine within 30 days prior to first dose, or planned receipt during the study period.
  • Pregnancy, breastfeeding, or unwillingness to use effective contraception during the study and for 6 months after the last dose.
  • Any condition that, in the opinion of the PI, would compromise participant safety or data integrity.

For Healthy Volunteers

  • Any current or unstable medical illness, including hepatic, renal, gastrointestinal, respiratory, cardiovascular (including ischemic heart disease), endocrine, neurologic (including history of severe head injury), immunologic, or hematologic disease.
  • Use of biologic therapies or immunosuppressive agents (PRN NSAIDs permitted).
  • Positive urine toxicology screen for illicit substances at screening.
  • Pregnancy at the time of baseline assessments (e.g., MRI).

Study Design

Enrollment

60 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Participants with MDD

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

no intervention: Healthy Control

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

Interventions

Tocilizumab

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

Primary outcome measure

  • Change in ventral stratal activation during reward processing (fMRI) [ Time Frame: at week 0 and week 10 ]

Central Contacts and Locations

Central contacts

Alexia Lizzano

3322437059alexia.lizzano@mssm.edu

Mackenzie Hargrove

3322437052mackenzie.brown@mssm.edu

Locations

Icahn School of Medicine at Mount Sinai

Recruiting

New York, New York, United States, 10029

Contacts

Mackenzie Hargrove

332-243-7052mackenzie.brown@mssm.edu

Matthew Dobbs

332-243-7055matthew.dobbs@mssm.edu

Principal Investigator:

James Murrough

More Information

Sponsor

Icahn School of Medicine at Mount Sinai

Last update posted

Apr 29, 2026

Last verified

Apr, 2026

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Icahn School of Medicine at Mount Sinai on 2026-04-29.