Evaluation of the Efficacy and Safety of Lysergide (MM120) in Adults with Generalized Anxiety Disorder: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this Phase 3 study is to evaluate the **efficacy** of a single dose of 100 µg MM120 compared to placebo on anxiety symptoms in adults with **Generalized Anxiety Disorder (GAD)** during a 12-week double-blind period. This is clinically relevant as it aims to determine the potential of MM120 as a therapeutic option for managing anxiety symptoms in GAD, a condition characterized by excessive and persistent worry that can significantly impair daily functioning.

Secondary objectives include:

• Evaluating 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.
• Assessing 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.
• Evaluating 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.
• Assessing 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.
• Evaluating the effect of 100 µg MM120 on sexual functioning in adults with GAD over a 40-week open-label period.

The clinical trial involves a total of **171 participants** diagnosed with **Generalized Anxiety Disorder (GAD)**. The study population includes both male and female adults aged between 18 and 74 years. Participants were selected based on specific inclusion criteria, including a confirmed diagnosis of GAD according to DSM-5 standards and a Hamilton Anxiety Rating Scale (HAM-A) Total Score of 20 or higher at screening and baseline. The trial population is required to have a body mass index (BMI) within the range of 18 to 38 kg/m². Participants must be in an acceptable overall medical condition and capable of providing informed consent. Additionally, they must have an adult support person available throughout the study. The trial does not specify any particular lifestyle considerations such as diet or physical activity. Both genders are included, and the study involves a vulnerable population, ensuring comprehensive monitoring and support throughout the trial period.

The clinical trial is a **Phase 3**, multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of the oral administration of MM120 in adults diagnosed with **Generalized Anxiety Disorder (GAD)**. The trial is structured into two parts: a 12-week double-blind period (Part A) followed by a 40-week open-label extension (Part B). The primary objective during Part A is to assess the efficacy of a single 100 µg dose of MM120 compared to placebo, with the primary endpoint being the change from baseline in the Hamilton Anxiety Rating Scale (HAM-A) total score at Week 12. Secondary endpoints include changes in HAM-A scores at various time points, as well as assessments using the Clinical Global Impressions (CGI) and Montgomery-Åsberg Depression Rating Scale (MADRS) among others.

Participants will be involved in the study for a total duration of up to 52 weeks, with the trial estimated to conclude by January 2027. The study begins with a screening visit to confirm eligibility based on criteria such as age, diagnosis of GAD, and HAM-A scores. Following successful screening, participants will be randomized to receive either MM120 or placebo. Study visits will occur at regular intervals throughout the double-blind period to monitor efficacy and safety, with assessments including HAM-A, CGI, and MADRS scores. The open-label extension will allow all participants to receive MM120, with visits continuing to assess long-term safety and efficacy.

Participants may be withdrawn from the study if they experience significant adverse events, fail to comply with study procedures, or if the investigator deems it necessary for their safety. The trial is designed to ensure rigorous monitoring and data collection to support the evaluation of MM120 as a potential treatment for GAD.

The clinical trial involves the administration of the experimental medication **MM120**, which is formulated as an **orodispersible tablet**. The active substance in MM120 is **lysergide**, also known as **lysergic acid diethylamide**. The medication is chemically synthesized and is provided by Mind Medicine, Inc. The trial protocol specifies that MM120 is to be administered orally. The dosing regimen includes a single dose of 100 micrograms (µg) of MM120, with a maximum total dose amounting to 500 µg over the course of the study. The treatment period is set for a maximum of 52 weeks. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the protocol.

In addition to the experimental treatment, a **placebo** is utilized as a comparator in this double-blind, placebo-controlled study. The placebo is designed to match the experimental medication in appearance but contains no active pharmaceutical ingredient. The placebo administration follows the same oral route and dosing schedule as MM120 to maintain the study's blinding integrity. The use of a placebo allows for the assessment of MM120's efficacy and safety in treating adults with **Generalized Anxiety Disorder** (GAD) by providing a baseline for comparison.

The efficacy of the investigational product, MM120, in the treatment of adults with Generalized Anxiety Disorder (GAD) will be assessed in a Phase 3, multicenter, randomized, double-blind, placebo-controlled study. The primary endpoint for efficacy evaluation during the double-blind period (Part A) is the change from baseline in the Hamilton Anxiety Rating Scale (HAM-A) total score at Week 12. Secondary endpoints include changes from baseline in HAM-A total score at Weeks 1, 2, 4, and 8, as well as HAM-A response/remission at each timepoint during the 12-week double-blind period. Additional secondary endpoints involve assessments using the Clinical Global Impressions-Improvement (CGI-I) Scale, Clinical Global Impressions-Severity (CGI-S) Scale, Patient Global Impression-Severity (PGI-S) Scale, Montgomery-Åsberg Depression Rating Scale (MADRS), Work Productivity and Activity Impairment (WPAI), and EQ-5D-5L at each timepoint throughout the double-blind period.

During the open-label extension (Part B), efficacy will be further evaluated by the percentage of participants requiring multiple doses of MM120, time to first treatment or discontinuation due to lack of efficacy, and the need for MM120 treatment as assessed by the average number of treatments. HAM-A response/remission and changes from double-blind baseline in CGI-S, PGI-S, MADRS, WPAI, and EQ-5D-5L scores will be assessed at each timepoint during the 40-week open-label period. The Changes in Sexual Functioning Questionnaire (CSFQ-14) total score and the percentage of men and women with normal and abnormal sexual functioning will also be evaluated at each timepoint during both the double-blind and open-label periods.