Targeting IL-17A for Treatment-Resistant Depression

NCT04979910 | Completed Phase 2 Results FDA Drug

• 1 other identifier: GCO 20-1909
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

The proposed study aims to test ixekizumab, a monoclonal antibody (mAb) against interleukin 17A (IL-17A), in patients with treatment-resistant depression (TRD).

Conditions

Major Depressive Disorder

Keywords

depression; investigational medication; treatment resistant depression; inflammation; ixekizumab; major depressive disorder

Outcome Measures

Primary Outcomes (2)

• Number of Participants Who Dropped-out

  The safety and feasibility of using ixekizumab in patients with TRD will be assessed by the completion of treatment measured as the receipt of all three Ixekizumab injections (160 mg at week 0, 80 mg at weeks 2 and 4). Drop-out rates will be calculated.

  6 weeks

• Number of Anticipated and Unanticipated Adverse Events

  The incidence and frequency of all anticipated and unanticipated serious and non-serious adverse events

  6 weeks

Secondary Outcomes (8)

• Change in Montgomery-Åsberg Depression Rating Scale Score - Response Rate

  Baseline and 6 weeks

• Change in Montgomery-Åsberg Depression Rating Scale Score - Remission Rate

  Baseline and 6 weeks

• Change in Quick Inventory of Depressive Symptomatology, Self-Report [QIDS-SR] Score

  Baseline and 6 weeks

• Change in Snaith-Hamilton Pleasure Scale (SHAPS)

  Up to Week 6

• Change in Temporal Experience of Pleasure Scale

  Baseline and 6 weeks

Study Arms (1)

Ixekizumab

EXPERIMENTAL

Ixekizumab 160 mg (two 80 mg injections) at Week 0, followed by 80 mg at Weeks 2 and 4 via subcutaneous route.

Drug: Ixekizumab

Interventions

Ixekizumab DRUG

a monoclonal antibody (mAb) against interleukin 17A (IL-17A)

Ixekizumab

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent (and assent when applicable) obtained from subject;
• Ability for subject to comply with the requirements of the study as determined by the PI;
• Men and women, age 18-70 years;
• Participants must meet DSM-5 criteria for Major Depressive Disorder \[MDD\]) in a current major depressive episode (MDE) as determined by a study psychiatrist and confirmed using the Structured Clinical Interview for DSM-5 Research Version (SCID-5-RV);
• Participants have had ≥ 2 adequate trials of antidepressants/augmentation strategies during current episode. (Refer to ATRQ Guidelines for Completion for guidelines on dose/duration required for a trial to be considered adequate.);
• Patients must be on a stable dose of antidepressant medication for \>4 weeks prior to randomization;
• Quick Inventory of Depressive Symptoms - Clinician Administered (QIDS-C) score ≥ 14
• 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 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.

You may not qualify if:

• A primary psychiatric diagnosis other than MDD as defined by DSM-5; \[comorbid anxiety disorders (including agoraphobia, generalized anxiety disorder, social anxiety disorder and panic disorder) and posttraumatic stress disorder (PTSD) are allowed\];
• Has a history of schizophrenia or other psychotic disorder, major depressive disorder with psychotic features, or bipolar I or II disorder;
• Diagnosis of a major neurocognitive disorder;
• Meets criteria for a moderate or severe substance use disorder within the past 6 months, with the exception of nicotine use disorder;
• The patient is pregnant or breastfeeding;
• Any contraindication to MRI or gadolinium including claustrophobia, any trauma or surgery which may have left magnetic material in the body, magnetic implants or pacemakers, inability to lie still for 1 hour or more, any known allergy to gadolinium;
• Positive urine toxicology screen for illicit drugs at the time of screening;
• Serious and imminent risk of self-harm or violence as determined by the PI;
• History of suicide attempt in the past 2 years or screening CSSRS Ideation Score \>2 in the past month;
• Clinically significant abnormalities of laboratory tests or physical examination;
• Any unstable medical illnesses including hepatic, renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease); endocrinologic, neurologic (including history of severe head injury), immunologic, or hematologic disease;
• Presence of TB as assessed by Quantiferon Gold test at screening;
• Concomitant treatments with other biologics or other immune-suppressant agents; PRN use of NSAIDs is permissible;
• Female participants who are pregnant, breastfeeding, or may become pregnant, or unwilling to practice birth control during participation in the study or the 6 months following;
• Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10025, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Depression; Depressive Disorder, Treatment-Resistant; Inflammation

Interventions

ixekizumab

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Esther Lee
• Organization: Icahn School of Medicine at Mount Sinai

esther.lee@mssm.edu

212-585-6133

Study Officials

• James W Murrough, MD, PhD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Psychiatry and Neuroscience

Model Details: This trial is a phase II, open-label trial where n=20 patients with treatment resistant depression will be treated with ixekizumab for 4 weeks and will undergo brain scans before and after the treatment period.

Study Record Dates

• First Submitted: July 19, 2021
• First Posted: July 28, 2021
• Study Start: August 27, 2021
• Primary Completion: April 12, 2024
• Study Completion: April 12, 2024
• Last Updated: May 20, 2025
• Results First Posted: May 20, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)