LYSERGIDE for Generalized anxiety disorder

Stratification factors

• site

Inclusion criteria

• {"criterion_text":"- 1. Participant must be between 18 and 74 years of age inclusive, at the time of signing the informed consent."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 2. Diagnosis of DSM-5 GAD based upon clinical assessment and confirmed by the Mini-International Neuropsychiatric Interview (MINI)."}
• {"criterion_text":"- 3. HAM-A Total Score ≥20 at Screening (Visit 1) and Baseline (Visit 2)."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 5. Participant meets independent assessment for eligibility."}
• {"criterion_text":"- 6. Body mass index (BMI) within the range ≥18 to ≤38 kg/m2 (inclusive) at Screening (Visit 1)."}
• {"criterion_text":"- 7. Male or female: Willingness to use medically acceptable forms of contraception, when applicable, for the duration of their participation."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 9. Must be in acceptable overall medical condition to participate in the study."}

Exclusion criteria

• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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. \tNOTE: 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 21. Initiated systematic psychotherapy within 4 weeks prior to Screening (Visit 1) or plans to initiate such therapy during the double-blind treatment period."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 25. Previous or current participation in any MM120 study."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 28. Women who are currently pregnant or breastfeeding or plan to become pregnant during the study."}
• {"criterion_text":"- 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.."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- 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."}

Primary endpoints

• {"endpoint_text":"- Double-blind Period (Part A): Change from Baseline in Hamilton Anxiety Rating Scale (HAM-A) total score at Week 12.","definition_or_measurement_approach":"Change from baseline in HAM-A total score at Week 12 measured by central rater-administered HAM-A (centralized raters independent of the site, blinded to treatment and visit number)."}

Secondary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Repeated measures of HAM-A total score at Weeks 1, 2, 4, 8; response/remission status per HAM-A at each timepoint; further details in protocol."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"CSFQ-14 total score change from baseline at scheduled timepoints; categorization of sexual functioning (normal/abnormal) by CSFQ-14 thresholds."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Proportion of participants receiving 1–5 doses over 52 weeks based on protocol-defined retreatment criteria evaluated during OLE; assessment based on GAD-7 triggers and central rater HAM-A confirmation per protocol."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Change from double-blind baseline in listed scales at scheduled OLE visits (HAM-A, MADRS, CGI-S, PGI-S, WPAI, EQ-5D-5L) per protocol assessment schedule."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"CSFQ-14 total score and categorization (normal/abnormal) at each OLE timepoint according to prespecified CSFQ scoring rules."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Change from baseline at specified timepoints in HAM-A and CGI-S; time-to-event analysis for first retreatment or lack of efficacy per protocol-defined criteria."}

Methods

• Website postings (site-specific recruitment material) — English and German versions referenced (documents: K2_Recruitment_material_Website_posting_site_03-03_specific_EN_Redacted, K2_Recruitment_material_Website_posting_site_03-03_specific_DE_Redacted).
• Recruitment flyers and posters (site-specific) — multiple EN/DE/CZE language flyers and posters listed for country-specific use (e.g., K2_Recruitment_material_Flyer_EN_Public, K2_Recruitment_material_Flyer_site_03-01_specific_DE_Redacted).
• GAD brochures and participant-facing informational brochures in multiple languages (GAD Brochure_Public, GAD_Brochure_DE_Public, K2_Recruitment material_GAD Brochure_Public) targeted to adults with generalized anxiety disorder.
• Participant Education Sessions (PES) and manuals for DSMs (Participant Education Session Manual_EN/DE_Redacted) used to educate potential participants prior to dosing.
• Phone screening / PS Script and Questionnaire (K2_PS_Script_Questionnaire_EN_Redacted and country-specific PS scripts) used to pre-screen and assess potential participants.
• Investigator memos and site-specific recruitment memos (e.g., K2_MM120-301_Recruitment material_Memo for Investigators_Redacted) to engage sites and local recruitment teams.

Poland

Earliest CTIS Part Ii Submission Date

04-02-2025

Latest Decision Or Authorization Date

29-08-2025

Processing Time Days

206

Number Of Sites

3

Number Of Participants

51

Czechia

Earliest CTIS Part Ii Submission Date

31-01-2025

Latest Decision Or Authorization Date

20-08-2025

Processing Time Days

202

Number Of Sites

4

Number Of Participants

48

France

Earliest CTIS Part Ii Submission Date

12-02-2025

Latest Decision Or Authorization Date

27-08-2025

Processing Time Days

196

Number Of Sites

5

Number Of Participants

54

Germany

Earliest CTIS Part Ii Submission Date

24-01-2025

Latest Decision Or Authorization Date

29-01-2026

Processing Time Days

370

Number Of Sites

4

Number Of Participants

48

Primary sponsor

Full Name

Definium Therapeutics US Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Syneos Health Inc.

Responsibilities

Sponsor duty code: 13 (role text not specified in record; Syneos Health functions as CRO/vendor contact listed).

Name

Worldwide Clinical Trials d.o.o.

Responsibilities

Multiple operational CRO responsibilities including vendor management and various operational services (codes 1,11,12,15,2,5,9).

Name

CTI Clinical Trial and Consulting Services Europe GmbH

Responsibilities

Pharmacovigilance and regulatory support.

Name

Pharpoint Research Inc.

Responsibilities

Clinical operations / site services (sponsor duty codes present: 10, 6).

Third parties

• {"country":"United States","full_name":"Assentia","duties_or_roles":"CDA management","organisation_type":"Industry"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"Sponsor duty code: 13 (role not text-specified in record)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Scarritt Group Inc.","duties_or_roles":"Investigator Meeting Services","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Germany","full_name":"CTI Clinical Trial and Consulting Services Europe GmbH","duties_or_roles":"Pharmacovigilance; additional sponsor duty code: 8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eclinical Solutions LLC","duties_or_roles":"EDC Build","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Iliomad Health Data","duties_or_roles":"Data Protection Officer","organisation_type":"Industry"}
• {"country":"United States","full_name":"Pharpoint Research Inc.","duties_or_roles":"Sponsor duties codes: 10 and 6 (roles not text-specified in record)","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Longboat Clinical Limited","duties_or_roles":"training platform/Learning management system","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Drug Safety Navigator LLC","duties_or_roles":"SUSAR submission in EudraVigilance","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"EMA Wellness LLC","duties_or_roles":"Central Rater eCOA / ePRO","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Labconnect LLC","duties_or_roles":"Health care - Laboratory/Research/Testing facility","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"Sponsor duties codes: 3 and 7 (roles not text-specified in record)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Catalent Cts (Edinburgh) Limited","duties_or_roles":"IMP Packaging / Labelling / Storage / Distribution","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"BSI Business Systems Integration AG","duties_or_roles":"Clinical Trial Management Systems","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Advarra Inc.","duties_or_roles":"Training platform/Learning management system","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Cardiac Safety services (L-ERT), Central ECG Reader","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Transperfect Translations International Inc.","duties_or_roles":"Translations","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Netherlands","full_name":"LabConnect Europe B.V.","duties_or_roles":"Health care - Laboratory/Research/Testing facility","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"LabConnect GmbH","duties_or_roles":"Health care - Laboratory/Research/Testing facility","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Croatia","full_name":"Worldwide Clinical Trials d.o.o.","duties_or_roles":"Multiple sponsor duties including vendor management, operational roles (codes 1,11,12,15,2,5,9).","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Canada","full_name":"Numinus","duties_or_roles":"Central DSM Training","organisation_type":"Industry"}