Major Depressive DisorderPhase 2NCT04827901
XEN1101 for Major Depressive Disorder
A Phase 2 study testing XEN1101 in people with Major Depressive Disorder, run by James Murrough at 2 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- XEN1101
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 2 sitesUnited States
- Study dates
- 19 Oct 2021to 7 Nov 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
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- 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;
- Extreme illness severity as defined by a CGI-S score >=6;
- Any current active suicidal ideation as measured by a Columbia Suicide Severity Rating Scale [C-SSRS] score of greater than 2 during the past month at the time of screening
- History of suicide attempt in past 2 years;
- Any unstable medical condition, including as follows; 19.1. History of skin or retinal pigment epithelium abnormalities caused by ezogabine; 19.2. Family history of sudden death of unknown cause; 19.3. Clinically significant abnormalities of laboratory tests, physical examination, or ECG; 19.4. History or presence of long QT syndrome; 19.5. QT corrected by Fridericia's formula (QTcF) > 450 msec; 19.6. Alanine transferase (ALT; SGPT) or aspartate transferase (AST; SGOT) levels >3 times the upper limit of normal (ULN) at screening;
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Baylor College of Medicine
Houston, Texas, 77030
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
About this study
Official title: A Proof of Concept Randomized Controlled Trial of XEN1101 for the Treatment of Major Depressive Disorder
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
- Being tested
- XEN1101, Placebo
- Keywords
- depression, anhedonia, major depressive disorder, investigational medication, potassium channel, KCNQ
- Medical subject headings
- Depressive Disorder, Major, Depression, Anhedonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
XEN1101Drug
two 10 mg capsules
PlaceboDrug
matching placebo
| Study group | Role | What they receive |
|---|---|---|
| XEN1101 | Active comparator | Subjects will take two 10 mg capsules of XEN1101 daily for 8 weeks for a total daily dose of 20 mg. Receives: Drug: XEN1101 |
| Placebo | Placebo comparator | Subjects will take a matching placebo daily for eight weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline (week 0), End of treatment (week 8)
Secondary outcomes (5)
Change in Montgomery-Åsberg Depression Rating Scale Score
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, higher score indicating poorer health outcomes. The MADRS provides a measure of the overall level of depression.
Measured: Baseline (week 0), End of treatment (week 8)
Change in Quick Inventory of Depressive Symptomatology, Self-Report [QIDS-SR] Score
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).
Measured: Baseline (week 0), End of treatment (week 8)
Change in Snaith-Hamilton Pleasure Scale (SHAPS)
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.
Measured: Baseline (week 0), End of treatment (week 8)
Change in Temporal Experience of Pleasure Scale
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. Total scores range is 16-108. Lower scores indicate greater levels of anhedonia.
Measured: Baseline (week 0), End of treatment (week 8)
Change in Clinical Global Impression Scale
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".
The degree of 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".
Measured: Baseline (week 0), End of treatment (week 8)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2021
- Study start19 Oct 2021
- Primary completion3 Oct 2024
- Study completion7 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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).
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- James Murrough
- Sponsor type
- University, hospital or other
- Collaborators
- Baylor College of Medicine, National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor-investigator, James Murrough, Icahn School of Medicine at Mount Sinai
- Investigators
- James W Murrough, MD, PhD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04827901
- Sponsor's protocol ID
- GCO 16-0374-02
- Other IDs
- 4R33MH111932-03
- Status last verified
- Mar 2025
- First submitted
- 30 Mar 2021
- Last updated
- 2 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All of the individual participant data collected during the trial, after deidentification.
Publications
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.
PubMed 41001561
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Proof of Concept Randomized Controlled Trial of XEN1101 for the Treatment of Major Depressive Disorder
- ClinicalTrials.gov ID
- NCT04827901
- Acronym / sponsor ID
- GCO 16-0374-02
- Conditions
- Major Depressive Disorder
- Keywords
- depression, anhedonia, major depressive disorder, investigational medication, potassium channel, KCNQ
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- James MurroughUniversity, hospital or other
- Collaborators
- Baylor College of Medicine, National Institute of Mental Health (NIMH)
- Study start
- 19 Oct 2021 (actual)
- Primary completion
- 3 Oct 2024 (actual)
- Study completion
- 7 Nov 2024 (actual)
- First posted
- 1 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 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).
| Arm | Type | Receives |
|---|---|---|
| XEN1101 | Active comparator | Drug: XEN1101Subjects will take two 10 mg capsules of XEN1101 daily for 8 weeks for a total daily dose of 20 mg. |
| Placebo | Placebo comparator | Drug: PlaceboSubjects will take a matching placebo daily for eight weeks. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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;
Key exclusion criteria (20 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| XEN1101two 10 mg capsules | Drug | XEN1101 |
| Placebomatching placebo | Drug | Placebo |
Primary outcome
Change in activation within the reward circuit by fMRI
Time frame: Baseline (week 0), End of treatment (week 8)
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.
5 secondary outcomes
Change in Montgomery-Åsberg Depression Rating Scale Score
Time frame: Baseline (week 0), End of treatment (week 8)
Change in Quick Inventory of Depressive Symptomatology, Self-Report [QIDS-SR] Score
Time frame: Baseline (week 0), End of treatment (week 8)
Change in Snaith-Hamilton Pleasure Scale (SHAPS)
Time frame: Baseline (week 0), End of treatment (week 8)
Change in Temporal Experience of Pleasure Scale
Time frame: Baseline (week 0), End of treatment (week 8)
Change in Clinical Global Impression Scale
Time frame: Baseline (week 0), End of treatment (week 8)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2025.
- Derived from this study: PubMed 41001561Murrough 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.
- Individual participant dataSharing planned: Yes. All of the individual participant data collected during the trial, after deidentification.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James W Murrough, MD, PhD principal investigator
Icahn School of Medicine at Mount Sinai
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing XEN1101 in people with Major Depressive Disorder, run by James Murrough at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in activation within the reward circuit by fMRI (time frame: Baseline (week 0), End of treatment (week 8)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04827901, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2025.