Study of NBI-1065845 as add-on treatment to prevent depression relapse in adults with Major Depressive Disorder who responded to initial treatment

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What is this study about?

This study focuses on people with Major Depressive Disorder (MDD) who have not responded well enough to their current antidepressant medications. The research evaluates a new medication called NBI-1065845, which is being tested as an additional treatment alongside existing antidepressant therapy. The study aims to determine if this new medication can help prevent depression symptoms from returning in people who have shown improvement with the treatment.

The study involves two phases. In the first phase, all participants receive NBI-1065845 along with their current antidepressant medication. Those who show improvement then continue to the second phase, where they are randomly assigned to either continue taking NBI-1065845 or receive a placebo, while maintaining their regular antidepressant medication. The treatment period lasts for 33 months.

The medication being studied, NBI-1065845, comes in tablet form and is taken by mouth. This research specifically looks at people who have experienced recurring episodes of moderate to severe depression or have persistent depressive symptoms, despite being on antidepressant treatment. The study will track how long it takes for depression symptoms to return, if they do, after participants start the second phase of the study.

1 Initial Evaluation

You will undergo a face-to-face evaluation using a special interview called Mini-International Neuropsychiatric Interview (MINI) to confirm your diagnosis of Major Depressive Disorder (MDD)

Your current depression symptoms will be evaluated using a rating scale called Hamilton Depression Rating Scale to ensure you meet the required score of 22 or higher

Your previous antidepressant treatment history will be reviewed using a questionnaire called Massachusetts General Hospital – Antidepressant Treatment Response Questionnaire

2 Open-label Treatment Phase

You will receive the study medication NBI-1065845 in tablet form, taken by mouth

During this phase, you will continue taking your current oral antidepressant medication

Your response to the treatment will be monitored to establish stability

3 Randomization Phase

If you show a stable response to the treatment, you will be randomly assigned to receive either:

– NBI-1065845 tablets to continue treatment

– Identical tablets without active medication (placebo)

You will not know which type of tablet you are receiving

4 Maintenance Phase

You will continue taking the assigned study medication (either NBI-1065845 or placebo)

Regular assessments will monitor your depression symptoms

The main focus will be on measuring how long it takes for depression symptoms to potentially return (relapse)

This phase will continue until the study ends in July 2028

Who Can Join the Study?

Must be at least 18 years old
Must sign an informed consent document showing you understand and agree to participate in the study
Must have a confirmed diagnosis of recurrent Major Depressive Disorder (moderate or severe) or persistent depressive disorder, verified through a face-to-face interview
Must be currently taking oral antidepressant medications as specified in the study protocol
Must have shown inadequate response to previous oral antidepressant treatments during current depression episode, as measured by a specific questionnaire (MGH-ATRQ)
Must score 22 or higher on the Hamilton Depression Rating Scale (a tool that measures depression severity) during screening and on the first day of the study
Must be willing and able to follow all study procedures and restrictions throughout the study period
Both men and women may participate in the study

Who Cannot Join the Study?

History of treatment-resistant Major Depressive Disorder (MDD), meaning depression that has not improved with at least two different antidepressant treatments
Current diagnosis of other psychiatric conditions besides depression, such as bipolar disorder (condition with both depression and high-energy periods), schizophrenia (condition affecting thoughts and behavior), or severe anxiety disorders
Significant risk of self-harm or suicide as determined by medical evaluation
Substance abuse or dependence within the past 6 months
Serious medical conditions that are not well-controlled, such as heart disease, liver problems, or kidney disease
Pregnancy, breastfeeding, or planning to become pregnant during the study period
Use of certain medications that might interact with the study drug
Participation in another clinical trial within the past 30 days
History of seizures or other neurological conditions that could affect brain function
Unstable or severe medical conditions that could interfere with study participation
Known allergies or sensitivity to similar medications
Unable to follow study procedures or attend regular study visits

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Rome	Italy
Gyncentrum Sp. z o.o.	Katowice	Poland
Centrum Zdrowia Alcea	Gdansk	Poland

Other Sites

Site Name	City	Country
Medical Center Hera EOOD	Sofia	Bulgaria
Diagnostics-Consultancy Center Mladost M Varna OOD	Varna	Bulgaria
Marienthali Kliinik OÜ	Tallin	Estonia
Arstikeskus Confido AS	Tallin	Estonia
Ospedale San Raffaele S.r.l.	Milan	Italy
Hospital Clinic De Barcelona	Barcelona	Spain
Tartu University Hospital	Tartu	Estonia
Diagnostic And Consultation Centre St.Vrach And St.St. Kuzma And Damian OOD	Sofia	Bulgaria
Medical Center Intermedica Ltd.	Sofia	Bulgaria
Hfafuq Pktcs Siio	Barcelona	Spain
Oyubuhw Bxmlp Keerszyzlaf Cisdtrvjz Suvs Eyi Gjphkzlroioru Mvhweqqfwm Tnsnccp	Bydgoszcz	Poland
Aulqvzd Oorzlhtpxcl Ufxqiucvidjmx Chhtpxbyizhe Dnthj Srwedk E Dwyop Ssvienz Dr Tajdwe	Turin	Italy
Pmylhckm Gkfdeahl Ldsslxiyi „lacufpfgkti Axox Asbsnolvp Trlkehh	Bialystok	Poland
Hfuyimfr Vmfi dufpkxnx	Barcelona	Spain

Trial status

Country	Status	Recruitment Start
Bulgaria	Recruiting	01.11.2025
Estonia	Recruiting	01.11.2025
Italy	Recruiting	01.11.2025
Poland	Recruiting	01.11.2025
Spain	Recruiting	01.11.2025

Trial locations

Investigated drugs:

9-(4-CYCLOHEXYLOXYPHENYL)-7-METHYL-3,4-DIHYDROPYRAZINO[2,1-C][1,2,4]THIADIAZINE 2,2-DIOXIDE

NBI-1065845 is an experimental medication being studied as an additional treatment for major depressive disorder (MDD). This medication is being tested alongside patients’ existing antidepressant treatments to see if it can help prevent depression symptoms from returning in people who have shown improvement. The medication is still being researched, and its common name has not yet been established, so it is known by its research code.

Placebo is used in this trial as a comparison to help determine how effective NBI-1065845 is at maintaining improvements in depression symptoms.

Investigated diseases:

Major depression

Major Depressive Disorder – A mental health condition characterized by persistent feelings of sadness, loss of interest in activities, and a range of emotional and physical symptoms that significantly affect daily life. The condition involves changes in mood, thinking, and behavior that last for at least two weeks or longer. People with this disorder often experience changes in sleep patterns, appetite, energy levels, and concentration. The disorder can develop gradually and may be triggered by life events, though sometimes there is no obvious cause. The illness tends to occur in episodes, which can vary in duration and intensity.

Trial ID:

2025-520541-72-00

Protocol code:

NBI-1065845-MDD3027

NCT ID:

NCT07196501

Trial Phase:

Therapeutic confirmatory (Phase III)

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Study of NBI-1065845 as add-on treatment to prevent depression relapse in adults with Major Depressive Disorder who responded to initial treatment

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?