Major Depressive DisorderPhase 3X-NOVA2NCT06775379
A Randomized Study of Azetukalner Versus Placebo in Major Depressive Disorder
A Phase 3 study testing Azetukalner in people with Major Depressive Disorder, run by Xenon Pharmaceuticals Inc. at 45 sites in United States.
Trial summary
X-NOVA2 is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the clinical efficacy, safety, and tolerability of azetukalner as a monotherapy in adult participants diagnosed with Major Depressive Disorder (MDD) Read more about this study
- Who is it for?
- Ages 18 to 74 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Azetukalner
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 450 participants
- Where
- 45 sitesUnited States
- Study dates
- 20 Dec 2024to Dec 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 74 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults ≥18 and ≤74 years of age and experienced their first major depressive episode (MDE) prior to 50 years of age
- Body Mass Index (BMI) ≤40 kg/m2
- Meets the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition Text Revised (DSM-5-TR) criteria for current major depressive disorder and is currently in an MDE, confirmed using the Mini International Neuropsychiatric Interview (MINI)
- Participant's current MDE has a duration of ≥6 weeks and ≤24 months.
Who cannot join
- Participant has a primary diagnosis of a mood disorder other than MDD.
- Participant has a history of any of the following: MDD with psychotic or catatonic features; MDD with mixed features; Bipolar I or II disorder; Obsessive-compulsive disorder; Schizophrenia, primary thought disorder, or other psychotic disorder.
- Participant has a current diagnosis of any of the following: MDD with seasonal pattern; Depression with peripartum or perimenopausal onset; Post traumatic stress disorder; Antisocial or borderline personality disorder (or presence of clinically significant borderline personality traits); Panic disorder and/or agoraphobia; ADHD treated with a psychostimulant, diagnosed during the current MDE, or with unstable symptoms, as judged by the investigator.
- Participant has a substance (excluding tobacco) or alcohol use disorder within the 12 months prior to screening.
- Participant has had an active suicidal plan/intent within the 6 months prior to screening, presence of suicidal behavior in the last 2 years, or >1 suicide attempt >24 years of age.
- Participant has a history of non-suicidal self-harm behavior in the 12 months prior to screening.
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- Participant has used antidepressants or other prohibited medications (including benzodiazepines), within the 2 weeks (4 weeks for fluoxetine) or within a period less than 5 times the drug's half-life, whichever is longer, prior to randomization.
- Participant has a history of non-response to ≥2 antidepressant drugs of adequate dose and duration in the current MDE as determined by the Antidepressant Treatment Response Questionnaire (ATRQ).
- Participants with medical conditions that may interfere with the purpose or conduct of the study
- Participant is pregnant, breastfeeding, or planning to become pregnant.
Trial locations and contacts
45 sites in 1 country.
45 sites in 1 country
United States45 sites
Lehigh Center For Clinical Research
Allentown, Pennsylvania, 18103
Advanced Discovery Research
Atlanta, Georgia, 30318
Synexus - Atlanta
Atlanta, Georgia, 30328
Northwest Clinical Trials Inc
Boise, Idaho, 83704
Boston Clinical Trials Llc
Boston, Massachusetts, 02131
Integrative Clinical Trials
Brooklyn, New York, 11229
New Hope Clinical Research
Charlotte, North Carolina, 28211
IMA Clinical Research
Chicago, Illinois, 60634
CNS Clinical Research Group
Coral Springs, Florida, 33067
Ct Clinical Research Associates
Cromwell, Connecticut, 06416
CenExel iResearch
Decatur, Georgia, 30030
Core Clinical Research
Everett, Washington, 98201
NeoClinical Research
Hialeah, Florida, 33016
Irvine Clinical Research
Irvine, California, 92614
Clinical Neuroscience Solutions, LLC
Jacksonville, Florida, 32256
Accel Research Sites Lakeland
Lakeland, Florida, 33803
Accel Research Sites - St. Petersburg-Largo
Largo, Florida, 33777
IMA Clinical Research Las Vegas
Las Vegas, Nevada, 89102
Redbird Research
Las Vegas, Nevada, 89119
Woodland International Research Group
Little Rock, Arkansas, 72211
CalNeuro Research Group, Inc.
Los Angeles, California, 90025
Psych Atlanta, Pc
Marietta, Georgia, 30060
Clinical Neuroscience Solutions, LLC
Memphis, Tennessee, 38119
PharmaSouth Research
Miami, Florida, 33165
Quantum Clinical Trials
Miami Beach, Florida, 33140
Neuro-Behavioral Clinical Research
North Canton, Ohio, 44720
Harmony Clinical Research Inc
North Miami Beach, Florida, 33162
Excell Research Inc.
Oceanside, California, 92056
Pahl Pharmaceutical Professionals Llc
Oklahoma City, Oklahoma, 73112
Atp Clinical Research
Orange, California, 92866
Nrc Research Institute
Orange, California, 92868
Clinical Neuroscience Solutions, LLC
Orlando, Florida, 32801
Combined Research Orlando Phase I-Iv
Orlando, Florida, 32807
Panhandle Research and Medical Clinic
Pensacola, Florida, 32503
Adams Clinical - Philadelphia
Philadelphia, Pennsylvania, 19104
IMA Clinical Research Phoenix
Phoenix, Arizona, 85012
Delricht Research - Plano
Plano, Texas, 75024
Woodland Research Northwest
Rogers, Arkansas, 72758
Cenexel Iresearch - Savannah
Savannah, Georgia, 31405
ELIXIA
Springfield, Massachusetts, 01103
Richmond Behavioral Associates
Staten Island, New York, 10314
CenExel CNS-TO (Collaborative Neuroscience Research)
Torrance, California, 90504
Sunwise Clinical Research
Walnut Creek, California, 94596
Kinetic Clinical Research, LLC
West Covina, California, 91790
Grayline Research Center
Wichita Falls, Texas, 76309
About this study
Official title: A Phase 3, Randomized, Double-blind, Placebo-Controlled, Multicenter Study to Evaluate Azetukalner in Moderate-to-Severe Major Depressive Disorder
X-NOVA2 is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the clinical efficacy, safety, and tolerability of azetukalner as a monotherapy in adult participants diagnosed with Major Depressive Disorder (MDD)
- Conditions
- Major Depressive Disorder
- Being tested
- Azetukalner, Placebo
- Keywords
- Depression, Antidepressant, XEN1101, Azetukalner
- Medical subject headings
- Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzetukalnerDrug
Also called XEN1101
Azetukalner 20 mg taken orally once a day with food (with the evening meal when possible) for 6 weeks
PlaceboDrug
Placebo taken orally once a day with food (with the evening meal when possible) for 6 weeks
| Study group | Role | What they receive |
|---|---|---|
| Azetukalner | Experimental | Azetukalner 20 mg Receives: Drug: Azetukalner |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in the Hamilton Depression Rating Scale, 17-item (HAMD-17) score at Week 6
The HAMD-17 consists of 17 items that are used to rate the severity of depression symptoms. Each item is scored in a range of 0 to 2 points or 0 to 4 points, with higher scores indicating a greater degree of depression. The score for each item is summed to compute a total score, which ranges from 0 to 52 points.
Measured: Baseline to Week 6
Secondary outcomes (4)
Change from baseline in the Snaith-Hamilton Pleasure Scale (SHAPS) score at Week 6
The SHAPS is a 14-item self-report questionnaire used to assess anhedonia. Each item on the SHAPS is worded so that higher scores indicate greater anhedonia. A total score can be derived by summing the responses to each item. Items answered with "strongly agree" are assigned a score of 1, while "strongly disagree" responses are assigned a score of 4 points. Total scores on the SHAPS can range from 14 to 56 points, with higher scores corresponding to higher levels of anhedonia.
Measured: Baseline to Week 6
Change from baseline in the Hamilton Depression Rating Scale, 17-item (HAMD-17) score at Week 1
The HAMD-17 consists of 17 items that are used to rate the severity of depression symptoms. Each item is scored in a range of 0 to 2 points or 0 to 4 points, with higher scores indicating a greater degree of depression. The score for each item is summed to compute a total score, which ranges from 0 to 52 points.
Measured: Baseline to Week 1
Change from baseline in the Clinical Global Impression of Severity (CGI-S) score at Week 6
The CGI-S is a clinician-rated global measure of participant overall disease severity. Participants are rated on a 7-point severity scale, with higher scores indicating more severe depression.
Measured: Baseline to Week 6
To assess the safety and tolerability of azetukalner (e.g., adverse events)
Measured: From screening (approximately 4 weeks prior to baseline) through to 8 weeks post-final dose.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2025
- Study start20 Dec 2024
- Primary completionOct 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 450 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xenon Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06775379
- Sponsor's protocol ID
- XPF-010-D301
- Acronym
- X-NOVA2
- Status last verified
- Oct 2026
- First submitted
- 9 Jan 2025
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Randomized, Double-blind, Placebo-Controlled, Multicenter Study to Evaluate Azetukalner in Moderate-to-Severe Major Depressive Disorder
- ClinicalTrials.gov ID
- NCT06775379
- Acronym / sponsor ID
- X-NOVA2 / XPF-010-D301
- Conditions
- Major Depressive Disorder
- Keywords
- Depression, Antidepressant, XEN1101, Azetukalner
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 450 participants (estimated)
- Lead sponsor
- Xenon Pharmaceuticals Inc.Industry (pharma, biotech, devices)
- Study start
- 20 Dec 2024 (actual)
- Primary completion
- Oct 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 15 Jan 2025 (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.
X-NOVA2 is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the clinical efficacy, safety, and tolerability of azetukalner as a monotherapy in adult participants diagnosed with Major Depressive Disorder (MDD)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Azetukalner | Experimental | Drug: AzetukalnerAzetukalner 20 mg |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 18 to 74 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Adults ≥18 and ≤74 years of age and experienced their first major depressive episode (MDE) prior to 50 years of age
- Body Mass Index (BMI) ≤40 kg/m2
- Meets the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition Text Revised (DSM-5-TR) criteria for current major depressive disorder and is currently in an MDE, confirmed using the Mini International Neuropsychiatric Interview (MINI)
- Participant's current MDE has a duration of ≥6 weeks and ≤24 months.
Key exclusion criteria (10 listed)
- Participant has a primary diagnosis of a mood disorder other than MDD.
- Participant has a history of any of the following: MDD with psychotic or catatonic features; MDD with mixed features; Bipolar I or II disorder; Obsessive-compulsive disorder; Schizophrenia, primary thought disorder, or other psychotic disorder.
- Participant has a current diagnosis of any of the following: MDD with seasonal pattern; Depression with peripartum or perimenopausal onset; Post traumatic stress disorder; Antisocial or borderline personality disorder (or presence of clinically significant borderline personality traits); Panic disorder and/or agoraphobia; ADHD treated with a psychostimulant, diagnosed during the current MDE, or with unstable symptoms, as judged by the investigator.
- Participant has a substance (excluding tobacco) or alcohol use disorder within the 12 months prior to screening.
- Participant has had an active suicidal plan/intent within the 6 months prior to screening, presence of suicidal behavior in the last 2 years, or >1 suicide attempt >24 years of age.
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 |
|---|---|---|
| AzetukalnerAlso: XEN1101Azetukalner 20 mg taken orally once a day with food (with the evening meal when possible) for 6 weeks | Drug | Azetukalner |
| PlaceboPlacebo taken orally once a day with food (with the evening meal when possible) for 6 weeks | Drug | Placebo |
Primary outcome
Change from baseline in the Hamilton Depression Rating Scale, 17-item (HAMD-17) score at Week 6
Time frame: Baseline to Week 6
The HAMD-17 consists of 17 items that are used to rate the severity of depression symptoms. Each item is scored in a range of 0 to 2 points or 0 to 4 points, with higher scores indicating a greater degree of depression. The score for each item is summed to compute a total score, which ranges from 0 to 52 points.
4 secondary outcomes
Change from baseline in the Snaith-Hamilton Pleasure Scale (SHAPS) score at Week 6
Time frame: Baseline to Week 6
Change from baseline in the Hamilton Depression Rating Scale, 17-item (HAMD-17) score at Week 1
Time frame: Baseline to Week 1
Change from baseline in the Clinical Global Impression of Severity (CGI-S) score at Week 6
Time frame: Baseline to Week 6
To assess the safety and tolerability of azetukalner (e.g., adverse events)
Time frame: From screening (approximately 4 weeks prior to baseline) through to 8 weeks post-final dose.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2026.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
45 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Azetukalner in people with Major Depressive Disorder, run by Xenon Pharmaceuticals Inc. at 45 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 4 inclusion and 10 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: under way, not looking for participants, as of the sponsor's last update on 13 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 45 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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 from baseline in the Hamilton Depression Rating Scale, 17-item (HAMD-17) score at Week 6 (time frame: Baseline to Week 6). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Oct 2026.