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NCT Number: NCT07592689

A Phase 3 Trial of DT120 for 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

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Key information

Conditions

Major Depressive Disorder Depressive Disorder Depressive Disorder, Major Mental Disorders Mood Disorders

Age range

18 year–74 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Lighthouse Psychiatry, Gilbert, Arizona, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

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

Treatment and study plan

Placebo

Other

A substance that is designed to have no therapeutic value

DT120

Drug

A psychoactive substance that mediates effects mainly through an agonist activity in the serotonin 2A receptor (5-HT2A)

Other names: MM120, lysergide tartrate

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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.

  2. 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.

  3. MADRS remission (total score ≤12) 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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).

  11. 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.

  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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. MADRS remission (total score ≤12) 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.

  19. 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.

  20. 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.

  21. 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.

  22. 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.

  23. 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.

  24. 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.

  25. 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).

  26. 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.

  27. 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Definium Therapeutics Clinical Trials Info Requests

CONTACT

[email protected]

1-332-282-0479

Sponsors and collaborators

Lead sponsor

Definium Therapeutics US, Inc.

Industry

Registry information

Official study title

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

Important dates

Study start
2026
Primary completion
2027
Study completion
2028
First posted
May 18, 2026
Registry last updated
Jul 30, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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