A Phase 3, Double-blind, Placebo-controlled Study (Part A) with an Open-label Extension (Part B) Evaluating MM120 Compared to Placebo in Generalized Anxiety Disorder – Panorama

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Definium Therapeutics US Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

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

Trial duration

20 Aug 2025 → ongoing

Decision date (initial)

2025-02-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Mind Medicine Inc.

External identifiers

EU CT number

2024-513572-17-00

WHO UTN

U1111-1309-7563

ClinicalTrials.gov

NCT06809595

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy, Pharmacokinetic

Double-blind Period (Part A): To evaluate the efficacy of a single dose of 100 μg MM120 versus placebo on anxiety symptoms in adults with GAD

Secondary objectives 6

1. Double-blind Period (Part A): To evaluate the efficacy of a single dose of 100 μg MM120 versus placebo on additional measures of anxiety, functioning, and quality of life in adults with GAD over the 12-week double-blind period.
2. Double-blind period (Part A): To evaluate the effect of a single dose of 100 μg MM120 versus placebo on sexual functioning in adults with GAD over the 12-week double-blind period.
3. Open-label Extension (Part B): To evaluate the maintenance of efficacy of 100 μg MM120 on anxiety symptoms in adults with GAD over a 40-week open-label follow-up period with retreatment.
4. Open-label Extension (Part B): To evaluate the efficacy of 100 μg MM120 on other measures of anxiety symptoms, functioning and quality of life in adults with GAD over a 40-week open-label follow-up period with retreatment.
5. Open-label Extension (Part B):To evaluate the effect of 100 μg MM120 on sexual functioning in adults with GAD over a 40-week open-label period.
6. Double-blind Period (Part A) key secondary: To evaluate the efficacy of a single dose of 100 μg MM120 versus placebo on additional measures of anxiety

Conditions and MedDRA coding

Generalized Anxiety Disorder (GAD)

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

Sponsor is committed to sharing individual participant data (IPD) from its clinical studies to promote transparency and facilitate further research. IPD includes anonymized demographic information, clinical assessments, treatment assignments, and patient-reported outcomes. Results of clinical studies will be provided on the publicly funded website ClinicalTrials.gov and the European Union Clinical Trials Register in line with applicable regulations. All data will be anonymized to protect participant confidentiality and comply with regulations. Sponsor commits to sharing upon request from qualified scientific researchers participant-level, study-level clinical study data, and protocol from clinical studies in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. All Sponsor-sponsored clinical studies are considered for publication in the scientific literature regardless of whether the results are positive or negative.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 1. Participant must be between 18 and 74 years of age inclusive, at the time of signing the informed consent.
2. 2. Diagnosis of DSM-5 GAD based upon clinical assessment and confirmed by the Mini-International Neuropsychiatric Interview (MINI).
3. 3. HAM-A Total Score ≥20 at Screening (Visit 1) and Baseline (Visit 2).
4. 4. MADRS Items 1, 7, and 8 are ≤2 at Screening (Visit 1) and Baseline (Visit 2). Note: participant must not currently meet criteria for a major depressive episode.
5. 5. Participant meets independent assessment for eligibility.
6. 6. Body mass index (BMI) within the range ≥18 to ≤38 kg/m2 (inclusive) at Screening (Visit 1).
7. 7. Male or female: Willingness to use medically acceptable forms of contraception, when applicable, for the duration of their participation.
8. 8. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.
9. 9. Must be in acceptable overall medical condition to participate in the study.
10. 10. Participant must have an adult support person/caregiver able to monitor them throughout the study, accompany them to and from visits where study drug is administered, and agree to be in personal contact with participant at least 3 days a week. This support person must be available throughout the clinical trial.

Exclusion criteria 29

1. 1. A psychiatric disorder, other than GAD, that was the primary focus of treatment as defined by the DSM-5 and assessed by the MINI within 6 months before Screening.
2. 2. First-degree relative with or lifetime history of a psychotic disorder (eg, schizophrenia, schizoaffective disorder, etc) or bipolar disorder based on the MINI and/or the psychiatric evaluation.
3. 3. Personal lifetime history of bipolar disorder I or II, post-traumatic stress disorder, or a personality disorder, based on the MINI and/or the psychiatric evaluation.
4. 4. Current psychiatric disorder that, in the opinion of the Investigator, is symptomatic in a manner that may confound the results of the study (eg, MDD, obsessive-compulsive disorder, dysthymic disorder, panic disorder, dissociative disorder, anorexia nervosa, or bulimia nervosa).
5. 5. Lifetime diagnosis of substance use disorder (excluding nicotine and caffeine), current diagnosis of alcohol use disorder, or treatment for alcohol or substance use disorder within (CCI) prior to Screening (Visit 1) as assessed by the MINI.
6. 6. Current diagnosis or history of neurological disorders including seizures (except febrile resolved before age 5): neurodegenerative disorders; movement disorders, traumatic brain injury (long-term impairment, currently symptomatic or in treatment), or any central nervous system (CNS) vascular disorders.
7. 7. Any clinically significant unstable illness. For example, hepatic impairment, renal insufficiency, gastrointestinal, cardiovascular, pulmonary, musculoskeletal, immunologic, endocrine, or metabolic disease that, in the opinion of the Investigator, may pose a risk to participation or confound the results of the study.
8. 8. Current clinically significant untreated sleep disorder that, in the opinion of the Investigator, may confound the results of the study (eg, obstructive sleep apnea, narcolepsy).
9. 9. Undiagnosed, untreated, or poorly controlled diabetes, defined as: glycosylated hemoglobin (HbA1C) ≥7% at Screening (Visit 1), without prior intervention. Note: participants with known stable diabetes with HbA1C ≥7% may be eligible if deemed not clinically significant by the Investigator.
10. 10. Significant loss of hearing or vision that, in the opinion of the Investigator, may confound the results of the study or interfere with the ability of the site staff to provide adequate oversight of the participant during the study.
11. 11. Major trauma or surgery in the 3 months prior to randomization, or has any surgery scheduled to occur during the study that would require an overnight hospital stay.
12. 12. Positive for hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus (HCV) antibodies at Screening, or are receiving treatment for Hepatitis B or C. Note: positive test results for participants who have previously recovered from or have been vaccinated for hepatitis are not exclusionary if participant is asymptomatic.
13. 13. Unstable human immunodeficiency virus (HIV) infection. Note: To be eligible, antiviral medication must be stable for 3 months prior to Screening and viral load undetectable at most recent check-up, within 6 months.
14. 14. History of malignancy or treatment of malignancy within 2 years prior to Screening, excluding resected basal cell or squamous cell carcinoma of the skin or carcinoma in situ (CIS) of the cervix that has been resolved without further treatment.
15. 15. Any of the following cardiovascular conditions: a. History of clinically significant arrhythmia (eg, long QT syndrome); valvular heart disease; pulmonary hypertension; treatment or hospitalization for a major cardiovascular event (eg, myocardial infarction, heart failure, stroke) within 1 year prior to Screening (Visit 1). b. Family history of significant arrhythmia or a first-degree relative with sudden, unexplained death under 40 years of age; history of unexplained syncopal episodes; uncontrolled hypokalemia or hypomagnesemia. c. Uncontrolled hypertension as determined by the Investigator, or blood pressure at the Screening visit above 140 mmHg systolic or 90 mmHg diastolic after approximately 5 minutes of rest. NOTE: This population may experience anxiety in medical settings. If the first measurement of a participant’s blood pressure is outside the allowable range, 2 additional recordings are allowed each after an additional approximately 5 minutes rest. d. Any abnormal ECG findings as determined by the central reader and confirmed as clinically significant by the Investigator in consultation with the contract research organization (CRO)’s Medical Monitor.
16. 16. One or more laboratory values outside the normal range at Screening (that are considered by the Investigator to be clinically significant); or has any of the following values at Screening: a. Serum creatinine value >1.5 x the upper limits of normal (ULN), b. Serum total bilirubin value >1.5 x ULN, c. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value >2 x ULN.
17. 17. Has risk of (CCI) based upon medical history or has active (CCI) from 6 months prior to Screening and up to Randomization, as defined by a “Yes” response to (CCI).
18. 18. Has either (CCI) or been hospitalized due to (CCI) within 5 years prior to Screening and up to Randomization as defined by medical history of (CCI) or a “Yes” response in the following (CCI).
19. 19. Treatment with deep brain stimulation (DBS), vagus nerve stimulation (VNS), electroconvulsive therapy (ECT), or transcranial magnetic stimulation (TMS) within 6 months prior to Screening or plan to receive treatment with any of these from the time of providing informed consent through End of Study (EOS).
20. 20. History of ketamine/esketamine use within the past (CCI) before Screening (including as part of a clinical study); or use of ketamine for treatment of an excluded condition.
21. 21. Initiated systematic psychotherapy within 4 weeks prior to Screening (Visit 1) or plans to initiate such therapy during the double-blind treatment period.
22. 22. Unwillingness or inability to discontinue prohibited concomitant medications, supplements, or other therapeutics (prescription or over-the-counter) including (CCI). Note: See Section 9.8 of the protocol for details of prohibited concomitant medications, supplements and other therapeutics, and allowable conditions of use. Participants may not discontinue standard of care medication if the purpose of the change is solely to enroll in the study and not medically indicated.
23. 23. Greater than (CCI) psychedelic use in the past 5 years. (CCI) psychedelic use in the past 2 years, including use as part of a clinical study.
24. 24. Any chronic medication that is not expected to remain stable throughout at least the end of the double-blind period or has not been stable for at least 4 weeks prior to Screening. Note: Adjustments to chronic medication may be allowed on a case-by-case basis during the OLE.
25. 25. Previous or current participation in any MM120 study.
26. 26. Previous participation in any clinical study for an investigational drug, device, or therapy within 6 months of Screening and throughout the duration of this study.
27. 27. Positive urine drug screen (UDS) for substances of abuse at Screening, Baseline, or Randomization. Note: Participants with a positive urine drug screen for cannabis or benzodiazepines or other prescribed medications at Screening may be eligible if they discontinue use and washout during the Screening period, if applicable.
28. 28. Women who are currently pregnant or breastfeeding or plan to become pregnant during the study.
29. 29. Participants who plan to donate sperm or eggs during the study, or who plan to donate sperm within 90 days or eggs within 30 days, respectively, after their last MM120 dose..

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Double-blind Period (Part A): Change from Baseline in Hamilton Anxiety Rating Scale (HAM-A) total score at Week 12.

Secondary endpoints 6

1. Double-blind Period (Part A): Change from Baseline in HAM-A total score at Week 8, Week 4, Week 2, and Week 1. HAM-A response/remission at each timepoint assessed during 12-week double-blind period. A full description of this endpoint can be found in the protocol.
2. Double-blind Period (Part A): Change from Baseline in the Changes in CSFQ-14 total score at each timepoint assessed during the double-blind period. Percent of men and women with normal and abnormal sexual functioning at each timepoint assessed during the double-blind period.
3. Open-label Extension (Part B): Percent of participants requiring 1, 2, 3, 4, or 5 doses of MM120 during the 52-week study as assessed by participants meeting protocol-specified retreatment criteria during the 40-week open-label period. . A full description of this endpoint can be found in the protocol.
4. Open label extension (Part B): Change from Double-blind Baseline at each timepoint assessed during the 40-week open-label period in the following: • HAM-A/ MADRS total score • CGI-S/ PGI-S Scale score • WPAI • EQ-5D-5L.
5. Open label extension (Part B): CSFQ-14 total score at each timepoint assessed during the open-label period. Percent of men and women with normal and abnormal sexual functioning at each timepoint assessed during the open-label period.
6. Double-blind Period (Part A) key secondary: Change from Baseline to Week 1 in HAM-A total score, to Week 12 in CGI-S scale score, to Day 2 in CGI-S score. Time to first retreatment or lack of efficacy

Investigational products

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

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Definium Therapeutics US Inc.

Sponsor organisation

Definium Therapeutics US Inc.

Address

1 World Trade Center Suite 8500

City

New York

Postcode

10007-0089

Country

United States

Scientific contact point

Organisation

Mind Medicine Inc.

Contact name

Medical Affairs

Public contact point

Organisation

Mind Medicine Inc.

Contact name

Clinical Trials Info Requests

Third parties 21

Locations

4 EU/EEA countries · 16 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 77 files

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

Application history

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