Evaluating NBI-1065845 as an Additional Treatment for Adults with Major Depressive Disorder Who Are Not Responding Adequately to Current Therapy

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What is this study about?

This clinical trial is investigating a medication called NBI-1065845 as an additional treatment for adults with Major Depressive Disorder (MDD). Major Depressive Disorder is a mental health condition characterized by persistent feelings of sadness, loss of interest in activities, and other symptoms that significantly affect daily functioning. The purpose of this study is to evaluate how effective and safe NBI-1065845 is when added to existing antidepressant treatments in people whose depression has not adequately responded to their current medication.

The study is designed as a randomized, double-blind trial where participants will receive either NBI-1065845 or a placebo alongside their current antidepressant medication. The treatment period will last for approximately 56 days (8 weeks), during which the medication’s effects on depression symptoms will be monitored.

Participants in this study must have recurrent MDD (occurring multiple times) that is moderate or severe, or persistent depressive disorder (a long-term form of depression). They must already be taking oral antidepressant treatments but experiencing an inadequate response to these medications despite proper dosing and duration.

1 Screening and Baseline

You will complete screening procedures to confirm you have Major Depressive Disorder (MDD) that meets study criteria. This includes a face-to-face evaluation using the Mini-International Neuropsychiatric Interview (MINI).

Your current antidepressant treatment will be assessed to confirm you have had an inadequate response to it, using a questionnaire called the Massachusetts General Hospital – Antidepressant Treatment Response Questionnaire.

You will need to have a Hamilton Depression Rating Scale score of 22 or higher at both screening and on Day 1 (baseline) of the study to qualify.

2 Randomization

You will be randomly assigned to receive either NBI-1065845 tablets or identical-looking placebo tablets (tablets without active medication).

You will not know which treatment you are receiving, as this is a double-blind study.

3 Treatment Period

You will take the study medication (NBI-1065845 or placebo) as an add-on treatment to your current antidepressant for 56 days (8 weeks).

Throughout this period, you will continue taking your current oral antidepressant medication as prescribed.

The study medication is in tablet form and will be taken according to the dosing schedule provided by the study staff.

4 Assessment Visits

You will attend regular assessment visits where your depression symptoms will be evaluated using various scales, primarily the Montgomery-Asberg Depression Rating Scale (MADRS).

Other assessments will include the Clinical Global Impression scale (CGI-S) and the Sheehan Disability Scale (SDS) to measure how your depression affects your daily functioning.

The main assessment will occur on Day 56 (after 8 weeks of treatment) to measure the change in your depression symptoms compared to baseline.

5 Safety Monitoring

Throughout the study, your safety will be monitored through regular assessments.

You should report any side effects or changes in your health to the study team.

6 Study Completion

After completing the 56-day treatment period, you will have a final assessment to evaluate the changes in your depression symptoms.

The primary measure will be the change in your MADRS score from the beginning to the end of the study.

Who Can Join the Study?

You must have completed the informed consent process.
You must be at least 18 years old when signing the informed consent.
You must have a primary diagnosis of recurrent Major Depressive Disorder (moderate or severe) or persistent depressive disorder. This diagnosis must be confirmed through a face-to-face evaluation using a specific psychiatric interview tool.
You must currently be taking oral antidepressant medication(s) as specified in the study protocol.
You must have had an inadequate response to oral antidepressant treatments that were given at adequate doses, for an adequate duration, and with proper adherence during your current episode of depression. This will be assessed using a specific questionnaire.
You must have a score of 22 or higher on the Hamilton Depression Rating Scale (a tool that measures depression severity) both at screening and on the first day of the study.
You must be willing and able to comply with all study procedures and restrictions according to the investigator’s judgment.

Who Cannot Join the Study?

Having a mental health condition other than Major Depressive Disorder (MDD).
Currently experiencing thoughts of harming yourself or others.
Having a history of suicide attempt in the past year or being at high risk for suicide.
Having a history of certain mental health conditions such as bipolar disorder, schizophrenia, or other psychotic disorders.
Having uncontrolled medical conditions like high blood pressure, diabetes, or thyroid problems.
Being pregnant, breastfeeding, or planning to become pregnant during the study.
Having a history of substance abuse or dependence in the past 6 months.
Currently using medications that might interact with the study drug.
Having participated in another clinical trial within the past 30 days.
Having already tried and failed 4 or more antidepressant treatments for your current depressive episode.
Being unable to comply with study procedures or visits.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country	Status
Nyiro Gyula Orszagos Pszichiatriai Es Addiktologiai Intezet	Budapest	Hungary

Other Sites

Site Name	City	Country
Sint-Lucas General Hospital	Brugge	Belgium
Anima	Alken	Belgium
Siguldas Slimnica	Siguldas Pagasts	Latvia
Gyongyosi Bugat Pal Korhaz	Gyongyos	Hungary
Obudai Egeszseguegyi Centrum Kft.	Dunaújváros	Hungary
Mehilaeinen Oy	Helsinki	Finland
Semmelweis University	Budapest	Hungary
Mcllmarq	Mechelen	Belgium
Dqd Mrsjs Ef Tincj Bun	Kalocsa	Hungary
Lw Kehvzu pwvrprud in Pjkkajmwss	Liepaja	Latvia
Ssqsthgu Guhckseqbpv Vzlg	Jelgava	Latvia
Smahg Pmbiysxyfteqzrrr Of	Kuopio	Finland
Oluo Mnfbmrwqhl Ow	Oulu	Finland

Trial status

Country	Status	Recruitment Start
Belgium	Recruiting	30.09.2025
Finland	Recruiting	30.09.2025
Hungary	Recruiting	30.09.2025
Latvia	Recruiting	30.09.2025

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 add-on treatment for people with Major Depressive Disorder (MDD) who are not getting enough relief from their current depression medication. It is being tested to see if it can help improve depression symptoms when used together with existing treatments.

Placebo is an inactive substance that looks identical to the study medication but contains no active ingredients. It is used as a comparison to determine whether the actual medication is effective.

Major Depressive Disorder – A mental health condition characterized by persistent feelings of sadness, loss of interest in activities once enjoyed, and a range of emotional and physical problems. It involves significant changes in how a person feels, thinks, and handles daily activities, with symptoms persisting for at least two weeks. Major Depressive Disorder affects sleep patterns, appetite, energy levels, concentration, and self-worth. The disorder often follows a course of recurring episodes, with each episode potentially increasing the risk for future ones. Symptoms may develop gradually and can vary in intensity from mild to severe.

Trial ID:

2024-519421-37-00

Protocol code:

NBI-1065845-MDD3026

NCT ID:

NCT06963021

Trial Phase:

Therapeutic confirmatory (Phase III)

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Evaluating NBI-1065845 as an Additional Treatment for Adults with Major Depressive Disorder Who Are Not Responding Adequately to Current Therapy

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?