Targeting IL-17A for Treatment-Resistant Depression

Sponsor

Icahn School of Medicine at Mount Sinai (Other)

Overall Status

Recruiting

CT.gov ID

NCT04979910

Collaborator

(none)

Enrollment

Location

Arms

25.1

Anticipated Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: Ixekizumab Drug: Placebo	Phase 2

Detailed Description

In the proposed study n=28 adult individuals with TRD will be treated with either ixekizumab or placebo for 4 weeks. Participants will complete screening procedures, body fluid analyses and brain imaging before and after treatment with ixekizumab or placebo.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

28 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This trial is a phase II, double-blind, randomized controlled trial where n=28 patients with treatment resistant depression will be treated with either ixekizumab or placebo for 4 weeks and will undergo brain scans before and after the treatment period.This trial is a phase II, double-blind, randomized controlled trial where n=28 patients with treatment resistant depression will be treated with either ixekizumab or placebo for 4 weeks and will undergo brain scans before and after the treatment period.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

An Experimental Therapeutics Study of a Monoclonal Antibody Against Interleukin 17A in Patients With Treatment-Resistant Depression

Actual Study Start Date :

Aug 27, 2021

Anticipated Primary Completion Date :

Oct 1, 2023

Anticipated Study Completion Date :

Oct 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Ixekizumab Ixekizumab 160 mg (two 80 mg injections) at Week 0, followed by 80 mg at Weeks 2 and 4 via subcutaneous route.	Drug: Ixekizumab a monoclonal antibody (mAb) against interleukin 17A (IL-17A)
Placebo Comparator: Placebo Matching saline placebo at Week 0 (two injections), followed by one injection at Weeks 2 and 4 via subcutaneous route.	Drug: Placebo matching placebo

Arm

Intervention/Treatment

Active Comparator: Ixekizumab

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

Drug: Ixekizumab

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

Placebo Comparator: Placebo

Matching saline placebo at Week 0 (two injections), followed by one injection at Weeks 2 and 4 via subcutaneous route.

Drug: Placebo

matching placebo

Outcome Measures

Primary Outcome Measures

Change in Montgomery-Åsberg Depression Rating Scale Score [Baseline and 6 weeks]
The Montgomery-Åsberg Depression Rating Scale (MADARS) is a 10-item instrument used for the evaluation of depressive symptoms in adults and for the assessment of any changes to those symptoms. Each of the 10 items is rated on a scale of 0 to 6, with differing descriptors for each item. These individual item scores are added together to form a total score, which can range between 0 and 60 points. The MADRS provides a measure of the overall level of depression. Higher score indicates poorer health outcome.

Secondary Outcome Measures

Change in Quick Inventory of Depressive Symptomatology, Self-Report [QIDS-SR] Score [Baseline and 6 weeks]
The Quick Inventory of Depressive Symptomatology, Self-Report (QIDS-SR) is a 16-item self-rated instrument designed to assess the severity of depressive symptoms. The 16 items cover the nine symptom domains of major depression and are rated on a scale of 0-3. Total score ranges from 0 to 27, with ranges of 0-5 (normal), 6-10 (mild), 11-15 (moderate), 16-20 (moderate to severe), and 21+ (severe). Higher score indicates poorer health outcome.
Change in Snaith-Hamilton Pleasure Scale (SHAPS) [Up to Week 6]
The Snaith-Hamilton Pleasure Scale (SHAPS) is a well-validated 14-item self-report questionnaire commonly used to assess anhedonia. Each item on the SHAPS is worded so that higher scores indicate greater pleasure capacity. A total score can be derived by summing the responses to each item. Items answered with "strongly agree" are coded as "1", while a "strongly disagree" response was assigned a score of "4." Total scores on the SHAPS can range from 14 to 56, with higher scores corresponding to higher levels of anhedonia.
Change in Temporal Experience of Pleasure Scale [Baseline and 6 weeks]
The Temporal Experience of Pleasure Scale (TEPS) is an 18-item self-report measurement of anhedonia which consists of a series of statements that must be rated according to how accurate they are for the individual. The scale produces a sub-score that differentiates the role of anticipatory pleasure ('wanting') and is derived of 10 items. Subscales scores from 9-54. Total scores range is 16-108. Lower scores indicate greater levels of anhedonia.
Change in Clinical Global Impression Scale [Baseline and 6 weeks]
This is a widely administered clinician rated scale that assesses the subject overall illness severity and the degree of improvement from the initial assessment. Illness severity is rated on a 1-7 scale where 1 corresponds to "Normal, Not at All Ill", 2 is "Borderline Mentally Ill", the anchor for 3 is "Mildly Ill", the anchor for 4 is "Moderately Ill", 5 is "Markedly Ill", 6 is "Severely Ill", and 7 is "Among the Most Extremely Ill Patients". Illness improvement is rated on a 1-7 scale where 1 corresponds to "Very Much Improved", 2 is "Much Improved", the anchor for 3 is "Minimally Improved", the anchor for 4 is "No Change", 5 is "Minimally Worse", 6 is "Much Worse", and 7 is "Very Much Worse".
Change in The Columbia-Suicide Severity Rating Scale (C-SSRS) [Baseline and 6 weeks]
The Columbia-Suicide Severity Rating Scale (C-SSRS) is a comprehensive, semi-structured interview that uniquely measures the full spectrum of suicidality including passive and active suicidal ideation, suicidal intent as well as suicidal behaviors. Full range from 0 to 9, with higher score indicating higher suicidal ideation severity.
Change in The Hamilton Anxiety Rating Scale (HAM-A) [Baseline and 6 weeks]
The Hamilton Anxiety Rating Scale (HAM-A) is a scale of assessments of anxiety states. The scale consists of 14 items, each defined by a series of symptoms, and measures both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. Higher score indicates poorer health outcomes.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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 18-65 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;
CRP level ≥ 2mg/L at screening;
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.

Exclusion Criteria:

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.