A Phase 3 Trial of MM120 for Major Depressive Disorder (Emerge)

Phase 3

Recruiting

• Conditions: Major Depressive Disorder
• Interventions: Other: Placebo; Drug: MM120 (LSD D-Tartrate)

• Registration Number: NCT06941844
• Lead Sponsor: Mind Medicine, Inc.

Brief Summary

A Phase 3 Double-blind, Placebo-controlled Study (Part A) with an Open-label Extension (Part B) Evaluating MM120 Compared to Placebo in Major Depressive Disorder - Emerge

Detailed Description

The study will enroll approximately 140 adult men and women 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 MM120 versus placebo, followed by a 40-week extension phase with the opportunity for open-label treatment. During this phase, participants will be monitored and evaluated for potential treatment with MM120 based on pre-specified safety and symptom severity criteria.

Study Timeline

• Status Verified: 2025-04
• Study Start: 2025-04-14
• Study First Submitted: 2025-04-16
• Study First Submitted QC: 2025-04-16
• Last Update Submitted: 2025-04-16
• Study First Posted: 2025-04-24
• Last Update Posted: 2025-04-24
• Primary Completion: 2026-11
• Study Completion: 2027-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 140

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1 - Placebo	Placebo	A substance that is designed to have no therapeutic value
Arm 2 - 100µg MM120 (LSD D-Tartrate)	MM120 (LSD D-Tartrate)	A psychoactive substance that mediates effects mainly through an agonist activity in the serotonin 2A receptor (5-HT2A)

Primary Outcome Measures

Name	Time	Method
Change from Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at Week 6	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 Outcome Measures

Name	Time	Method
Change from Baseline in the MADRS total score at Week 12, Week 4, Week 2, and Week 1	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.
MADRS response (reduction from Baseline score of ≥50%) at each timepoint assessed during the 12-week double-blind period	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.
MADRS remission (total score ≤10) at each timepoint assessed during the 12-week double-blind treatment period	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.
Clinical Global Impression - Improvement (CGI-I) Scale score at each timepoint assessed during the 12-week double-blind period	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.
Change from Baseline throughout the 12-week double-blind period at each timepoint assessed in Clinical Global Impression - Severity (CGI-S) Scale score	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.
Change from Baseline throughout the 12-week double-blind period at each timepoint assessed in Patient Global Impression - Severity (PGI-S) Scale score	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.
Change from Baseline throughout the 12-week double-blind period at each timepoint assessed in MADRS-6	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.
Change from Baseline throughout the 12-week double-blind period at each timepoint assessed in Hamilton Anxiety Rating Scale (HAM-A)	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.
Change from Baseline throughout the 12-week double-blind period at each timepoint assessed in -Work Productivity and Activity Impairment Questionnaire (WPAI)	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.
Change from Baseline throughout the 12-week double-blind period at each timepoint assessed in -EuroQol-5 Dimensions - 5 Levels (EQ-5D-5L)	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).
Change from Baseline in the Changes in Sexual Functioning Questionnaire (CSFQ-14) total score at each timepoint assessed during the double-blind period	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.
Percent of men and women with normal and abnormal sexual functioning at each timepoint assessed during the double-blind period	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.
Percent of participants requiring one, two, three, four, or five doses of MM120 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	Percent of participants requiring one, two, three, four, or five doses of MM120 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 to first treatment or lack of efficacy in the open-label period (Part B)	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.
Need for MM120 treatment as assessed by the average number of MM120 treatments during the study	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.
MADRS response (reduction from Baseline score of ≥50%) at each timepoint assessed during the 40-week open-label period	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.
MADRS remission (total score ≤10) at each timepoint assessed during the 40-week open-label period	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
Change from Double-blind Baseline throughout the 40-week open-label period at each timepoint assessed in MADRS total score	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.
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	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.
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	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.
Change from Double-blind Baseline throughout the 40-week open-label period at each timepoint assessed in MADRS-6 total score	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.
Change from Double-blind Baseline throughout the 40-week open-label period at each timepoint assessed in HAM-A total score	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.
Change from Double-blind Baseline throughout the 40-week open-label period at each timepoint assessed in WPAI	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.
Change from Double-blind Baseline throughout the 40-week open-label period at each timepoint assessed in EQ-5D-5L	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).
CSFQ-14 total score at each timepoint assessed during the open-label period	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.
Percent men and women with normal and abnormal sexual functioning at each timepoint assessed during the open-label period	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.

Trial Locations

Locations (21)

Preferred Research Partner; 🇺🇸 Fayetteville, Arkansas, United States

Preferred Research Partners, Inc; 🇺🇸 Little Rock, Arkansas, United States

Kadima Neuropsychiatry Institute; 🇺🇸 La Jolla, California, United States

Pacific Neuroscience Institute at Providence Saint John's; 🇺🇸 Santa Monica, California, United States

Mountain View Clinical Research, Inc; 🇺🇸 Denver, Colorado, United States

Clinical Neuroscience Solutions, Inc; 🇺🇸 Memphis, Tennessee, United States

Segal Trials- Center for Psychedelic Research; 🇺🇸 Lauderhill, Florida, United States

Uptown Research; 🇺🇸 Chicago, Illinois, United States

Sheppard Pratt; 🇺🇸 Baltimore, Maryland, United States

Copley Clinical; 🇺🇸 Boston, Massachusetts, United States

Adams Clinical; 🇺🇸 Boston, Massachusetts, United States

University of Missouri; 🇺🇸 Columbia, Missouri, United States

Cenexel HRI; 🇺🇸 Berlin, New Jersey, United States

Berman Clinical; 🇺🇸 New York, New York, United States

Columbia - New York State Psychiatric Institute; 🇺🇸 New York, New York, United States

Neuro-Behavioral Clinical Research; 🇺🇸 Canton, Ohio, United States

University of Cincinnati; 🇺🇸 Cincinnati, Ohio, United States

Dell Medical School, University of Texas at Austin; 🇺🇸 Austin, Texas, United States

Austin Clinical Trial Partners; 🇺🇸 Austin, Texas, United States

Cedar Clinical Research; 🇺🇸 Murray, Utah, United States

Memory Clinic, Inc; 🇺🇸 Bennington, Vermont, United States