Clinical trial NCT04979910: Targeting IL-17A for Treatment-Resistant Depression
Official title: An Experimental Therapeutics Study of a Monoclonal Antibody Against Interleukin 17A in Patients With Treatment-Resistant Depression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Major Depressive Disorder
Keywords: depression
investigational medication
treatment resistant depression
inflammation
ixekizumab
major depressive disorder
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
First posted: 2021-07-28
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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.
Primary purpose: TREATMENT

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).

Detailed description: In the proposed study n=20 adult individuals with TRD will be treated with ixekizumab for 4 weeks. Participants will complete screening procedures, body fluid analyses and brain imaging before and after treatment with ixekizumab.

Eligibility criteria: 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 18-70 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.

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.

Primary outcomes:
measure: Number of Participants Who Dropped-out
timeFrame: 6 weeks
measure: Number of Anticipated and Unanticipated Adverse Events
timeFrame: 6 weeks
Secondary outcomes:
measure: Change in Montgomery-Åsberg Depression Rating Scale Score - Response Rate
timeFrame: Baseline and 6 weeks
measure: Change in Montgomery-Åsberg Depression Rating Scale Score - Remission Rate
timeFrame: Baseline and 6 weeks
measure: Change in Quick Inventory of Depressive Symptomatology, Self-Report [QIDS-SR] Score
timeFrame: Baseline and 6 weeks
measure: Change in Snaith-Hamilton Pleasure Scale (SHAPS)
timeFrame: Up to Week 6
measure: Change in Temporal Experience of Pleasure Scale
timeFrame: Baseline and 6 weeks
measure: Change in Clinical Global Impression Scale
timeFrame: Baseline and 6 weeks
measure: Change in The Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline and 6 weeks
measure: Change in The Hamilton Anxiety Rating Scale (HAM-A)
timeFrame: Baseline and 6 weeks
Other outcomes:
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: James W Murrough, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: