XEN1101 for Major Depressive Disorder

NCT04827901 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: GCO 16-0374-024R33MH111932-03
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 2

Brief Summary

This project is designed to examine the neuronal KCNQ2/3 potassium (K+) channel subtype as a novel treatment target for mood disorders through the administration of the KCNQ-selective channel opener XEN1101 (Xenon Pharmaceuticals).

Conditions

Major Depressive Disorder

Keywords

depression; anhedonia; major depressive disorder; investigational medication; potassium channel; KCNQ

Outcome Measures

Primary Outcomes (1)

• Change in activation within the reward circuit by fMRI

  The change in activation within the bilateral ventral striatum (VS) from baseline (week 0) to end of treatment (week 8) as measured by fMRI during an Incentive Flanker Task.

  Baseline (week 0), End of treatment (week 8)

Secondary Outcomes (5)

• Change in Montgomery-Åsberg Depression Rating Scale Score

  Baseline (week 0), End of treatment (week 8)

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

  Baseline (week 0), End of treatment (week 8)

• Change in Snaith-Hamilton Pleasure Scale (SHAPS)

  Baseline (week 0), End of treatment (week 8)

• Change in Temporal Experience of Pleasure Scale

  Baseline (week 0), End of treatment (week 8)

• Change in Clinical Global Impression Scale

  Baseline (week 0), End of treatment (week 8)

Study Arms (2)

XEN1101

ACTIVE COMPARATOR

Subjects will take two 10 mg capsules of XEN1101 daily for 8 weeks for a total daily dose of 20 mg.

Drug: XEN1101

Placebo

PLACEBO COMPARATOR

Subjects will take a matching placebo daily for eight weeks.

Drug: Placebo

Interventions

XEN1101 DRUG

two 10 mg capsules

XEN1101

Placebo DRUG

matching placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 65 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 18-65 years;
• Participants must meet DSM-5 criteria for current depressive disorder (major depressive disorder \[MDD\]) in a 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);
• Clinically significant anhedonia as determined by a SHAPS score ≥ 20 at screening;
• Current illness severity is at least moderate, defined as a score of ≥4 on the CGI-S Scale;
• 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.

You may not qualify if:

• A primary psychiatric diagnosis other than MDD as defined by DSM-5;
• Has a history of schizophrenia or other psychotic disorder, major depressive disorder with psychotic features, or bipolar I or II disorder.
• History of non-response to \>4 adequate antidepressant trials in the current episode as determined by the Antidepressant Treatment Response Questionnaire (ATRQ);
• History of non-response to electroconvulsive therapy in the current depressive episode;
• A current diagnosis of depression with peripartum onset;
• Diagnosis of a major neurocognitive disorder;
• Meets criteria for a substance use disorder within the past 6 months, with the exception of nicotine use disorder;
• Patient shows signs of retinal macular disease, or retinal pigment epithelium abnormality prior to randomization.
• Male patients, if heterosexually active with partner who is female of childbearing potential, pregnant, or breastfeeding, who are unwilling to 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 who are unwilling to 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.
• 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;
• Inability to swallow capsules;
• Any contraindication to MRI including claustrophobia, any trauma or surgery which may have left magnetic material in the body, magnetic implants or pacemakers, and inability to lie still for 1 hour or more;
• Positive urine toxicology screen for drugs of abuse at the time of screening\*;
• Use of any dis-allowed medication according to the study protocol\*\*;
• Serious and imminent risk of self-harm or violence as determined by the PI;

Sponsors & Collaborators

• James Murrough: lead
• Baylor College of Medicine: collaborator
• National Institute of Mental Health (NIMH): collaborator

Study Sites (2)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Murrough J, Fremont R, Neukam P, Govindarajulu U, Ables J, Hameed S, Corwin M, Hargrove M, Chang H, Boukezzi S, Kelly C, Swann A, Salas R, Amarneh D, Engelhardt J, Weyland A, Bagiella E, Morris L, Mathew S. A Randomized, Controlled Trial of the Novel, Potent Kv7 Channel Opener Azetukalner in Individuals with Major Depressive Disorder and Anhedonia: Neural Response to Reward, Clinical Outcomes, and Safety. Res Sq [Preprint]. 2025 Sep 15:rs.3.rs-7448148. doi: 10.21203/rs.3.rs-7448148/v1.

  PMID: 41001561 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major; Depression; Anhedonia

Interventions

XEN1101

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 W Murrough, MD, PhD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor, Psychiatry

Model Details: This is a phase II, randomized, parallel-arm, placebo-controlled clinical trial were 60 patients with major depressive disorder will be randomized in 1:1 fashion to XEN1101 (N=30) or matching placebo (N=30).

Study Record Dates

• First Submitted: March 30, 2021
• First Posted: April 1, 2021
• Study Start: October 19, 2021
• Primary Completion: October 3, 2024
• Study Completion: November 7, 2024
• Last Updated: April 2, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Immediately following publication. No end date.
• Access Criteria: Investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose. Any purpose. Other NDCT Database

Locations

US (2)