Evaluation of Troriluzole as Adjunctive Therapy in Patients with Obsessive Compulsive Disorder with Inadequate Response to Standard Treatment

The primary objective of this study is to evaluate the **efficacy** of troriluzole as an adjunctive therapy compared to placebo in subjects with **Obsessive Compulsive Disorder** (OCD) who have had an inadequate response to their current OCD treatment. This is assessed based on the change in their Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score. The clinical relevance of this objective lies in determining whether troriluzole can provide additional therapeutic benefits for patients with OCD who do not respond sufficiently to standard treatments.

Secondary objectives include:

• Assessing the **safety** and tolerability of troriluzole relative to placebo in subjects with OCD.
• Evaluating the efficacy of troriluzole compared to placebo on functional disability as measured by the Sheehan Disability Scale (SDS).
• Evaluating the efficacy of troriluzole compared to placebo on global clinical condition as measured by the Clinical Global Impression-Severity Scale (CGI-S).

The clinical trial involves a total of **600 participants** diagnosed with **Obsessive Compulsive Disorder (OCD)**. The study population includes both male and female subjects, with an age range of 18 to 64 years. Participants were selected based on their primary diagnosis of OCD, confirmed by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and a minimum illness duration of one year. All subjects are currently experiencing a non-response or inadequate response to their existing standard of care medication, as indicated by a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) total score of 22 or higher, reflecting moderate to severe OCD symptoms. Participants are required to be on a stable dose of an SSRI (excluding fluvoxamine), clomipramine, venlafaxine, or desvenlafaxine monotherapy. The trial includes a vulnerable population, ensuring a comprehensive evaluation of the efficacy of troriluzole as an adjunctive therapy compared to placebo. Lifestyle factors such as diet and physical activity were not specified in the trial data provided.

The clinical trial is designed as a **randomized, double-blind, placebo-controlled** study to evaluate the efficacy of **troriluzole** as an adjunctive therapy in individuals diagnosed with **Obsessive Compulsive Disorder (OCD)**. The trial aims to assess the change in the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score, with the primary endpoint being the improvement in obsessive-compulsive symptomatology. Secondary endpoints include changes from baseline in the Sheehan Disability Scale (SDS) total score and the Clinical Global Impressions (CGI) Severity score. The trial is expected to run from January 15, 2021, to June 13, 2025, with a maximum treatment period of 10 weeks for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a primary diagnosis of OCD and a Y-BOCS total score of 22 or higher. Following randomization, participants will receive either troriluzole or a placebo, administered orally in capsule form. The study includes regular follow-up visits to monitor efficacy and safety, with assessments conducted at specified intervals. The end-of-study visit will conclude the participant's involvement, during which final evaluations will be performed.

The expected length of participant involvement is approximately 10 weeks, contingent upon adherence to the study protocol. Conditions that may lead to early termination from the study include significant adverse events, non-compliance with study procedures, or withdrawal of consent. The trial is conducted under the sponsorship of Biohaven Pharmaceuticals, Inc., with the investigational product being administered in doses of up to 140 mg daily, depending on the treatment group assignment.

The clinical trial involves the administration of **Troriluzole**, a chemical compound developed by Biohaven Pharmaceuticals, Inc. Troriluzole is provided in a **capsule** form and is intended for oral administration. The trial includes two dosage regimens of Troriluzole: one with a maximum daily dose of 140 mg and a total maximum dose of 280 mg over a 10-day period, and another with a maximum daily dose of 100 mg and a total maximum dose of 200 mg over the same period. The administration of Troriluzole is conducted orally, and the treatment period is limited to 10 days. The study aims to evaluate the efficacy of Troriluzole as an adjunctive therapy in subjects with Obsessive Compulsive Disorder (OCD) who have shown an inadequate response to their current treatment.

The trial also includes a **placebo** group to serve as a comparator for the efficacy assessment of Troriluzole. The placebo is designed to match the BHV-4157 capsules in appearance and is administered in the same manner as the active drug, ensuring the double-blind nature of the study. The placebo capsules are available in 100 mg and 140 mg dosages, corresponding to the active treatment dosages, and are administered orally over the same 10-day period. The use of a placebo control allows for a rigorous evaluation of the treatment's efficacy by comparing changes in the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores between the active and placebo groups.

The efficacy of **troriluzole** as an adjunctive therapy in the treatment of Obsessive Compulsive Disorder (OCD) will be assessed in a randomized, double-blind, placebo-controlled clinical trial. The primary endpoint for evaluating efficacy is the improvement in obsessive-compulsive symptomatology, which will be measured by the change from baseline in the total score of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Secondary endpoints include the change from baseline on the Sheehan Disability Scale (SDS) total score and the Clinical Global Impressions (CGI) Severity score.

Participants in the trial will have a primary diagnosis of OCD as per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, confirmed by the MINI at screening. They must have experienced an inadequate response to their current standard of care medication, with a Y-BOCS total score of 22 or higher at screening and baseline, indicating moderate or severe OCD symptoms. The trial will involve subjects currently on an SSRI (excluding fluvoxamine), clomipramine, venlafaxine, or desvenlafaxine monotherapy for an adequate duration and dose as defined by the clinical trial protocol.

The trial is designed to evaluate the efficacy of troriluzole over a maximum treatment period of 10 weeks. Efficacy assessments will be conducted at specified timepoints throughout the study to monitor changes in the Y-BOCS, SDS, and CGI scores, providing a comprehensive evaluation of the therapeutic impact of troriluzole compared to placebo in subjects with OCD.