Evaluation of Efficacy and Safety of Milsaperidone as Adjunctive Therapy in Patients With Major Depressive Disorder

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Vanda Pharmaceuticals Netherlands B.V.

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

26 Sep 2025 → ongoing

Decision date (initial)

2025-06-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Vanda Pharmaceuticals Inc.

External identifiers

EU CT number

2024-520333-68-00

ClinicalTrials.gov

NCT06830044

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy, Pharmacogenetic, Pharmacogenomic, Pharmacokinetic

To evaluate the efficacy of milsaperidone as an adjunctive treatment to antidepressant therapy for patients with Major Depressive Disorder (MDD) as measured by change from baseline to Week 6 in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score.

Secondary objectives 6

1. To evaluate the efficacy of milsaperidone as an adjunct to antidepressant therapy for patients with MDD as measured by change from baseline in the Clinical Global Impression of Severity (CGI-S)
2. To evaluate the efficacy of milsaperidone as an adjunct to antidepressant therapy for patients with MDD as measured by improvements in the Clinical Global Impression of Change (CGI-C)
3. To evaluate the efficacy of milsaperidone as an adjunct to antidepressant therapy for patients with MDD as measured by change from baseline in MADRS Total Score
4. To assess the safety and tolerability of milsaperidone compared to placebo adjunct to antidepressant therapy in the treatment of MDD as measured by spontaneous reporting of adverse events (AEs)
5. To evaluate the effect of milsaperidone on serum urate levels as measured by change from baseline analysis and frequency of shifts above upper limit normal
6. To evaluate the effect of milsaperidone/urate interaction with factors such as genetic variants and demographics, on serum urate levels as measured by change from baseline analysis, and frequency of shifts above the upper limit normal

Conditions and MedDRA coding

Major Depressive Disorder

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Meets DSM-5-TR criteria for MDD as confirmed by the Investigator and/or Sponsor-approved interviewer/rater via both: the Structural Clinical Interview for DSM-5, Clinical Trials Version (SCID-5-CT), updated for DSM-5-TR, and review of the patient’s medical records/history (a phone call with the patient’s physician may be acceptable in lieu of medical records), or, if lacking adequate records, written approval from the Sponsor or Sponsor’s Designee;
2. The start of the current major depressive episode (MDE) is at least 8 weeks but no more than 24 months prior to screening;
3. Rater-administered MADRS total score ≥ 24 at Screening and at Baseline;
4. CGI-S – Severity of Illness score of ≥ 4 at Screening and Baseline;
5. Quick Inventory of Depressive Symptomatology-Self Report-16 item (QIDS-SR-16) score ≥ 14 at Screening and at Baseline;
6. Currently having an inadequate response to antidepressant therapy (less than 50% improvement), as confirmed by the Investigator using the Antidepressant Treatment Response Questionnaire (ATRQ) and taking at least the minimum effective dose (per package insert) of one of the following antidepressants as monotherapy treatment for at least 6 weeks duration prior to the Screening Visit: bupropion, citalopram, duloxetine, escitalopram, fluoxetine, levomilnacipran (if locally approved for MDD), milnacipran (if locally approved for MDD), paroxetine, sertraline, venlafaxine, desvenlafaxine, vilazodone, vortioxetine

Exclusion criteria 6

1. Within the patient's lifetime, has a confirmed DSM-5-TR psychiatric diagnosis other than MDD, including: Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder or other psychotic disorder; Bipolar Disorder;
2. Diagnosis of any current (within 6 months) psychiatric diagnosis other than MDD that has been confirmed by DSM-5-TR including: Anxiety disorders such as Panic Disorder or Generalized Anxiety Disorder; Obsessive-compulsive Disorder; Posttraumatic Stress Disorder. Note: Anxiety symptoms may be allowed if secondary to MDD, provided these symptoms do not require concurrent treatment; Patients with history of GAD documented on their MR may be included if the Investigator provides sufficient evidence that the diagnosis is no longer applicable. Eating disorder; Personality disorder of sufficient severity to have a major impact on the patient's psychiatric status;
3. Experiences a ≥ 25% decrease in the MADRS total score between Screening and Baseline;
4. Experiences a ≥ 25% decrease in the QIDS-SR-16 total score between Screening and Baseline;
5. In the opinion of the Investigator, has a significant risk for suicidal behavior during participation in the study or is considered to be in imminent danger to themselves or others. Any of the following categorically exclude a patient from participation: at Screening, the patient scores "yes" on Suicidal Ideation Items 4 or 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) within 6 months prior to Screening, or at Baseline, the patient scores "yes" on Suicidal Ideation Items 4 or 5 since the Screening Visit; at Screening, the patient has had 1 or more suicide attempts within 2 years prior to Screening; or at Screening or Baseline, the patient scores ≥ 5 on MADRS Item 10 (Suicidal Thoughts).
6. Has a first MDE at age 60 years or older.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Vanda Pharmaceuticals Netherlands B.V.

Sponsor organisation

Vanda Pharmaceuticals Netherlands B.V.

Address

Basisweg 10

City

Amsterdam

Postcode

1043 AP

Country

Netherlands

Scientific contact point

Organisation

Vanda Pharmaceuticals Netherlands B.V.

Contact name

Vanda Pharmaceuticals

Public contact point

Organisation

Vanda Pharmaceuticals Netherlands B.V.

Contact name

Vanda Pharmaceuticals

Third parties 1

Locations

3 EU/EEA countries · 25 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 28 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications