A Phase 3 Trial of DT120 for Major Depressive Disorder (Ascend)

May 12, 2026 updated by: Definium Therapeutics US, Inc.

A Phase 3 Multicenter, Randomized, Double-blind, Placebo-controlled, 12-Week Study (Part A) With a 40-Week Open-label Extension (Part B) Evaluating the Efficacy and Safety of Oral DT120 Compared to Placebo in the Treatment of Adults With Major Depressive Disorder - Ascend

A Phase 3 Double-blind, Placebo-controlled Study (Part A) with an Open-label Extension (Part B) Evaluating DT120 Compared to Placebo in Major Depressive Disorder - Ascend

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The study will enroll approximately 165 participants aged 18 to 74 years, inclusive, with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) confirmed primary diagnosis of MDD, a minimum MADRS total score of at least 26 and a CGI-S score of at least 4 at Screening and Baseline without clinically relevant medical or psychiatric history.

The study consists of a 12-week randomized, double-blind, single-dose administration period evaluating DT120 versus placebo, followed by a 40-week Extension Phase (EP) with opportunity for open-label treatment during which participants will be monitored and evaluated for potential retreatment with DT120 based on pre-specified safety and symptom severity criteria.

Study Type

Interventional

Enrollment (Estimated)

165

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Arizona
      • Gilbert, Arizona, United States, 85234
    • Arkansas
      • Little Rock, Arkansas, United States, 72211
    • California
      • San Francisco, California, United States, 94158
        • Not yet recruiting
        • UCSF Department of Neurology
        • Contact:
      • Santa Monica, California, United States, 90404
        • Not yet recruiting
        • Psychedelic Science Institute
        • Contact:
    • Colorado
      • Denver, Colorado, United States, 80209
        • Recruiting
        • Mountain View Clinical Research, Inc
        • Contact:
    • Florida
    • Georgia
      • Atlanta, Georgia, United States, 30331
        • Recruiting
        • CenExel Atlanta
        • Contact:
      • Decatur, Georgia, United States, 30030
        • Recruiting
        • CenExel Decatur
        • Contact:
      • Savannah, Georgia, United States, 31405
        • Recruiting
        • CenExel Savannah
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60640
    • Massachusetts
      • Boston, Massachusetts, United States, 02116
    • New York
      • New York, New York, United States, 10029
    • Ohio
      • Cleveland, Ohio, United States, 44113
        • Not yet recruiting
        • Cleveland Clinic
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • Adams Clinical Philadelphia
        • Contact:
    • South Carolina
    • Utah
      • Draper, Utah, United States, 84020
      • Orem, Utah, United States, 84058
    • Washington
      • Vancouver, Washington, United States, 98661
        • Not yet recruiting
        • VA Portland Healthcare System
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Diagnosis of MDD per DSM-5
  2. Male or female aged 18 to 74
  3. Currently experiencing a major depressive episode (MDE) of ≥8 weeks and ≤24 months duration
  4. MADRS Total Score ≥26
  5. CGI-S Score ≥4

Exclusion Criteria:

  1. Certain psychiatric disorders (other than major depressive disorder)
  2. First degree relative with or lifetime history of a psychotic disorder or bipolar disorder
  3. Current diagnosis of alcohol or substance use disorder (excluding nicotine and caffeine
  4. Any clinically significant unstable illness

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Arm 1 - Placebo
A substance that is designed to have no therapeutic value
Other: Placebo
A substance that is designed to have no therapeutic value
Sham Comparator: Arm 2 - 50µg DT120
A psychoactive substance that mediates effects mainly through an agonist activity in the serotonin 2A receptor (5-HT2A)
Drug: DT120
A psychoactive substance that mediates effects mainly through an agonist activity in the serotonin 2A receptor (5-HT2A)
Other Names:
  • lysergide tartrate
  • MM120
Experimental: Arm 3 - 100µg DT120
A psychoactive substance that mediates effects mainly through an agonist activity in the serotonin 2A receptor (5-HT2A)
Drug: DT120
A psychoactive substance that mediates effects mainly through an agonist activity in the serotonin 2A receptor (5-HT2A)
Other Names:
  • lysergide tartrate
  • MM120

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at Week 6
Time Frame: Baseline to Week 6
The MADRS is used to assess depression severity and to detect changes due to antidepressant treatment. The MADRS includes 10 clinician-completed items. Each of the 10 questions is scored with a range of 0-6 points. An item score of 0 indicates item not present or normal, while an item score of 6 indicates severe or continuous presence of the symptoms. The total possible score is 60, and higher scores represent a more severe condition.
Baseline to Week 6

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Global Impression - Improvement (CGI-I) Scale score at each timepoint assessed during the 12-week double-blind period
Time Frame: Day 2 to Week 12
The CGI-I scale is used to measure the clinician's assessment of how much the participant's illness has improved or worsened relative to Baseline (Visit 2). The CGI-I comprises one item with 7 possible ratings (1-7 points), where a lower score indicates improvement, and a higher score indicates worsening.
Day 2 to Week 12
Change from Baseline throughout the 12-week double-blind period at each timepoint assessed in Clinical Global Impression - Severity (CGI-S) Scale score
Time Frame: Baseline to Week 12
The CGI-S scale assesses the clinician's impression of the participant's current severity of illness relative to the clinician's experience with patients who have the same diagnosis. The CGI-S comprises one item with 7 possible ratings (1-7 points), where a higher score indicates more severe illness.
Baseline to Week 12
Change from Baseline throughout the 12-week double-blind period at each timepoint assessed in Patient Global Impression - Severity (PGI-S) Scale score
Time Frame: Baseline to Week 12
The PGI scale is the patient-reported outcome (PRO) counterpart to the CGI scale. The PGI-S comprises one participant-completed item with 5 possible ratings (1-5) where a higher score indicates more severe illness.
Baseline to Week 12
Change from Baseline in the Changes in Sexual Functioning Questionnaire (CSFQ-14) total score at each timepoint assessed during the double-blind period
Time Frame: Baseline to Week 12
The CSFQ-14 is a structured self-reported questionnaire designed to measure illness- and medication-related changes in sexual functioning that consists of 14 items measuring sexual functioning as a total score (14 items). There is a male and female version of the CSFQ-14 scale and a total score of less than 47 for men and less than 41 for women indicates sexual dysfunction. Lower scores are associated with worsened sexual functioning.
Baseline to Week 12
Percent of men and women with normal and abnormal sexual functioning at each timepoint assessed during the double-blind period
Time Frame: Baseline to Week 12
The CSFQ-14 is a structured self-reported questionnaire designed to measure illness- and medication-related changes in sexual functioning that consists of 14 items measuring sexual functioning as a total score (14 items). There is a male and female version of the CSFQ-14 scale and a total score of less than 47 for men and less than 41 for women indicates sexual dysfunction. Lower scores are associated with worsened sexual functioning.
Baseline to Week 12
Change from Double-blind Baseline throughout the 40-week open-label period at each timepoint assessed in Clinical Global Impression - Severity (CGI-S) Scale score
Time Frame: Baseline to Week 52
The CGI-S scale assesses the clinician's impression of the participant's current severity of illness relative to the clinician's experience with patients who have the same diagnosis. The CGI-S comprises one item with 7 possible ratings (1-7 points), where a higher score indicates more severe illness.
Baseline to Week 52
Change from Double-blind Baseline throughout the 40-week open-label period at each timepoint assessed in Patient Global Impression - Severity (PGI-S) Scale score
Time Frame: Baseline to Week 52
The PGI scale is the patient-reported outcome (PRO) counterpart to the CGI scale. The PGI-S comprises one participant-completed item with 5 possible ratings (1-5) where a higher score indicates more severe illness.
Baseline to Week 52
Change from Double-blind Baseline throughout the 40-week open-label period at each timepoint assessed in MADRS total score
Time Frame: Baseline to Week 52
The MADRS is used to assess depression severity and to detect changes due to antidepressant treatment. The MADRS includes 10 clinician-completed items. Each of the 10 questions is scored with a range of 0-6 points. An item score of 0 indicates item not present or normal, while an item score of 6 indicates severe or continuous presence of the symptoms. The total possible score is 60, and higher scores represent a more severe condition.
Baseline to Week 52
Change from Double-blind Baseline throughout the 40-week open-label period at each timepoint assessed in EQ-5D-5L
Time Frame: Baseline to Week 52
The EuroQol 5 Dimension 5 Level (EQ-5D-5L) is a self-reported outcome measure used to evaluate health outcomes over a wide range of health conditions and treatments. The EQ-5D consists of the EQ-5D descriptive system and the EQ visual analogue scale (VAS).
Baseline to Week 52
Percent men and women with normal and abnormal sexual functioning at each timepoint assessed during the open-label period
Time Frame: 40 week open label period
The CSFQ-14 is a structured self-reported questionnaire designed to measure illness- and medication-related changes in sexual functioning that consists of 14 items measuring sexual functioning as a total score (14 items). There is a male and female version of the CSFQ-14 scale and a total score of less than 47 for men and less than 41 for women indicates sexual dysfunction. Lower scores are associated with worsened sexual functioning.
40 week open label period
Change from Baseline in the MADRS total score at Week 12, Week 4, Week 2, and Week 1
Time Frame: Week 12, Week 4, Week 2, and Week 1
The MADRS is used to assess depression severity and to detect changes due to antidepressant treatment. The MADRS includes 10 clinician-completed items. Each of the 10 questions is scored with a range of 0-6 points. An item score of 0 indicates item not present or normal, while an item score of 6 indicates severe or continuous presence of the symptoms. The total possible score is 60, and higher scores represent a more severe condition.
Week 12, Week 4, Week 2, and Week 1
MADRS response (reduction from Baseline score of ≥50%) at each timepoint assessed during the 12-week double-blind period
Time Frame: Baseline to Week 12
The MADRS is used to assess depression severity and to detect changes due to antidepressant treatment. The MADRS includes 10 clinician-completed items. Each of the 10 questions is scored with a range of 0-6 points. An item score of 0 indicates item not present or normal, while an item score of 6 indicates severe or continuous presence of the symptoms. The total possible score is 60, and higher scores represent a more severe condition.
Baseline to Week 12
MADRS remission (total score ≤10) at each timepoint assessed during the 12-week double-blind treatment period
Time Frame: Baseline to Week 12
The MADRS is used to assess depression severity and to detect changes due to antidepressant treatment. The MADRS includes 10 clinician-completed items. Each of the 10 questions is scored with a range of 0-6 points. An item score of 0 indicates item not present or normal, while an item score of 6 indicates severe or continuous presence of the symptoms. The total possible score is 60, and higher scores represent a more severe condition.
Baseline to Week 12
Change from Baseline throughout the 12-week double-blind period at each timepoint assessed in MADRS-6
Time Frame: Baseline to Week 12
The MADRS-6 is a subscale of the 10-item MADRS and evaluates the core symptoms of depression: apparent sadness, reported sadness, inner tension, lassitude, inability to feel, and pessimistic thought.
Baseline to Week 12
Change from Baseline throughout the 12-week double-blind period at each timepoint assessed in Hamilton Anxiety Rating Scale (HAM-A)
Time Frame: Baseline to Week 12
The HAM-A consists of the following 14 items that encompass both psychological and somatic symptoms of anxiety. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.
Baseline to Week 12
Time to first treatment or lack of efficacy in the open-label period (Part B)
Time Frame: Day 1 to Week 52
Measured as time from first dosing in the Double-blind period to participant meeting MADRS criteria for re-dose or meeting criteria for lack of efficacy.
Day 1 to Week 52
MADRS response (reduction from Baseline score of ≥50%) at each timepoint assessed during the 40-week open-label period
Time Frame: 40-week open label period
The MADRS is used to assess depression severity and to detect changes due to antidepressant treatment. The MADRS includes 10 clinician-completed items. Each of the 10 questions is scored with a range of 0-6 points. An item score of 0 indicates item not present or normal, while an item score of 6 indicates severe or continuous presence of the symptoms. The total possible score is 60, and higher scores represent a more severe condition.
40-week open label period
Change from Double-blind Baseline throughout the 40-week open-label period at each timepoint assessed in MADRS-6 total score
Time Frame: Baseline to Week 52
The MADRS-6 is a subscale of the 10-item MADRS and evaluates the core symptoms of depression: apparent sadness, reported sadness, inner tension, lassitude, inability to feel, and pessimistic thought.
Baseline to Week 52
Change from Double-blind Baseline throughout the 40-week open-label period at each timepoint assessed in HAM-A total score
Time Frame: Baseline to Week 52
The HAM-A consists of the following 14 items that encompass both psychological and somatic symptoms of anxiety. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.
Baseline to Week 52
Change from Baseline throughout the 12-week double-blind period at each timepoint assessed in - Work Productivity and Activity Impairment: Specific Health Problem Questionnaire (WPAI-SHP)
Time Frame: Baseline to Week 12
The WPAI-SHP is a 6-item questionnaire, with a recall period of the past 7 days. The WPAI measures impairments in both paid work and unpaid work. It measures absenteeism, presenteeism as well as impairment in unpaid activity because of the health problem under study.
Baseline to Week 12
Change from Baseline throughout the 12-week double-blind period at each timepoint assessed in - EuroQol-5 Dimensions - 5 Levels (EQ-5D-5L)
Time Frame: Baseline to Week 12
The EuroQol 5 Dimension 5 Level (EQ-5D-5L) is a self-reported outcome measure used to evaluate health outcomes over a wide range of health conditions and treatments. The EQ-5D consists of the EQ-5D descriptive system and the EQ visual analogue scale (VAS).
Baseline to Week 12
Percent of participants requiring one, two, three, four, or five doses of DT120 during the 52-week study (Part A and Part B) as assessed by participants meeting protocol-specified retreatment criteria during the 40-week open-label period
Time Frame: Day 1 to Week 52
Percent of participants requiring one, two, three, four, or five doses of DT120 during the 52-week study (Part A and Part B) as assessed by participants meeting protocol-specified retreatment criteria during the 40-week open-label period.
Day 1 to Week 52
Need for DT120 treatment as assessed by the average number of DT120 treatments received
Time Frame: Day 1 to Week 52
Average number of treatments assessed from first dose in the double-blind period through completion of the open label extension.
Day 1 to Week 52
Single dose durability as assessed by time to event where moderate or worse MDD symptoms resurfaced
Time Frame: Day 1 to Week 52
Measured as time from first dosing in the Double-blind period to participant meeting MADRS criteria for re-dose or meeting criteria for lack of efficacy.
Day 1 to Week 52
MADRS remission (total score ≤10) at each timepoint assessed during the 40-week open-label period
Time Frame: 40-week open label period
The MADRS is used to assess depression severity and to detect changes due to antidepressant treatment. The MADRS includes 10 clinician-completed items. Each of the 10 questions is scored with a range of 0-6 points. An item score of 0 indicates item not present or normal, while an item score of 6 indicates severe or continuous presence of the symptoms. The total possible score is 60, and higher scores represent a more severe condition.
40-week open label period
Change from Double-blind Baseline throughout the 40-week open-label period at each timepoint assessed in WPAI-SHP
Time Frame: Baseline to Week 52
The WPAI-SHP is a 6-item questionnaire, with a recall period of the past 7 days. The WPAI measures impairments in both paid work and unpaid work. It measures absenteeism, presenteeism as well as impairment in unpaid activity because of the health problem under study.
Baseline to Week 52
Change from Baseline in the Changes in Sexual Functioning Questionnaire (CSFQ-14) total score at each timepoint assessed during the open-label period
Time Frame: 40 week open label period
The CSFQ-14 is a structured self-reported questionnaire designed to measure illness- and medication-related changes in sexual functioning that consists of 14 items measuring sexual functioning as a 27 total score (14 items). There is a male and female version of the CSFQ-14 scale and a total score of less than 47 for men and less than 41 for women indicates sexual dysfunction. Lower scores are associated with worsened sexual functioning.
40 week open label period

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Definium Therapeutics US, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 10, 2026

Primary Completion (Estimated)

September 1, 2027

Study Completion (Estimated)

June 1, 2028

Study Registration Dates

First Submitted

May 12, 2026

First Submitted That Met QC Criteria

May 12, 2026

First Posted (Actual)

May 18, 2026

Study Record Updates

Last Update Posted (Actual)

May 18, 2026

Last Update Submitted That Met QC Criteria

May 12, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MM120-311

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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