Major Depressive DisorderPhase 3X-NOVA3NCT07076407
A Randomized Study of Azetukalner Versus Placebo in Major Depressive Disorder (X-NOVA3)
A Phase 3 study testing Azetukalner in people with Major Depressive Disorder, run by Xenon Pharmaceuticals Inc. at 50 sites in 7 countries.
Trial summary
X-NOVA3 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
- 50 sitesin 7 countries
- Study dates
- 8 Jul 2025to Jul 2027
- 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
50 sites in 7 countries.
50 sites in 7 countries
United States35 sites
Delricht Research
Atlanta, Georgia, 30329
Emory University Brain Health Center
Atlanta, Georgia, 30329
Austin Clinical Trial Partners
Austin, Texas, 78737
Pharmasite Research Inc.
Baltimore, Maryland, 21208-6605
Clinical Innovations Inc
Bellflower, California, 90706
Pillar Clinical Research
Bentonville, Arkansas, 72712
Adams Clinical Boston
Boston, Massachusetts, 02116
SanRo Clinical Research Group
Bryant, Arkansas, 72022
Magnolia Clinical Research, Llc
Cary, North Carolina, 27511
Lumina Clinical Research Center
Cherry Hill, New Jersey, 08002
Harmonex Neuroscience Research
Dothan, Alabama, 36303
Gulfcoast Clinical Research Center
Fort Myers, Florida, 33912
Sarkis Clinical Trials
Gainesville, Florida, 32607
Institute of Living
Hartford, Connecticut, 06106
University of Alabama at Birmingham, Huntsville Regional Medical Campus
Huntsville, Alabama, 35801
Insight Clinical Trials
Independence, Ohio, 44195
Smart Trials, LLC
Jefferson, Louisiana, 70121
Center for Neurohealth
La Jolla, California, 93037
Activmed Practices & Research, Llc - Methuen
Methuen, Massachusetts, 01844
Bioscience Research, LLC
Mount Kisco, New York, 10549
Fieve Clinical Research, Inc.
New York, New York, 10017
IMA Clinical Research
New York, New York, 10128
Psychiatric Care and Research Center
O'Fallon, Missouri, 63368
Sooner Clinical Research
Oklahoma City, Oklahoma, 73116
Advanced Quality Medical Research
Orland Park, Illinois, 60462
Princeton Medical Institute
Princeton, New Jersey, 08540
Boeson Research
Provo, Utah, 84604
Equipath Health and Research Tampa Bay, Llc
Riverview, Florida, 33578
St. Charles Psychiatric Associates - Midwest Research Group
Saint Charles, Missouri, 63304
Artemis Institute for Clinical Research
San Diego, California, 92103
California Neuroscience Research
Sherman Oaks, California, 91403
Bio Behavioral Health
Toms River, New Jersey, 08755
Pacific Clinical Research Management Group
Upland, California, 91786
Adams Clinical Watertown
Watertown, Massachusetts, 02472
Vitalix Clinical, Inc
Worcester, Massachusetts, 01608
Poland4 sites
In Vivo Sp. z.o.o.
Bydgoszcz, 85-048
Clinical Medical Research Sp. z o.o.
Katowice, 40156
Praktyka Lekarska Malgorzata Wojtanowska-Bogacka
Poznan, 60192
Specjalistyczna Praktyka Lekarska, Filip Rybakowski
Poznan, 60744
Romania3 sites
Centru De Evaluare Si Tratament A Toxicodependentenlor Pentru Tineri Sf. Stelian
Bucharest, 011216
Clinica Nutrimed Cercetare Sr
Bucharest, 020744
Institutul Privat De Cercetari Melchisedec (ICPM) Pentru Boli Autoimune Ereditare si Rare - ICPM
Craiova, 200157
Finland2 sites
Suomen Terveystalo Oy
Helsinki, 00180
Oulu Mentalcare Oy
Oulu, 90100
Germany2 sites
Charite - Universitatsmedizin Berline
Berlin, 10117
Boehm-Peters PartGmbB - Praxis fur Psychiatrie, Psychotherapie, Neurologie
Rosenheim, 83022
Slovakia2 sites
Dana Ignjatovićová, spol. s r.o
Banská Bystrica, 97401
Liptovska Nemocnica S Poliklinikou Mudr. Ivana Stodolu Liptovsky Mikulas
Liptovský Mikuláš, 03123
Spain2 sites
Hospital Universitari Vall D'Hebron
Barcelona, 8035
Hospital Universitario Son Espases
Palma de Mallorca, 07120
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-NOVA3 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 posted22 Jul 2025
- Study start8 Jul 2025
- Primary completionMay 2027 (estimated)
- Study completionJul 2027 (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
- NCT07076407
- Sponsor's protocol ID
- XPF-010-D302
- Acronym
- X-NOVA3
- Status last verified
- Oct 2026
- First submitted
- 14 Jul 2025
- Last updated
- 15 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 15 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
- NCT07076407
- Acronym / sponsor ID
- X-NOVA3 / XPF-010-D302
- 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
- 8 Jul 2025 (actual)
- Primary completion
- May 2027 (estimated)
- Study completion
- Jul 2027 (estimated)
- First posted
- 22 Jul 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-NOVA3 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 15 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.
50 sites in 7 countries: 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 50 sites in 7 countries.
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 15 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 50 sites in United States, Poland, Romania, Finland, Germany and 2 more countries. 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 15 Oct 2026.