Troriluzole (BHV-4157) in Adult Participants With Obsessive Compulsive Disorder

A Randomized, Double-blind, Placebo-controlled Trial of Adjunctive Troriluzole in Obsessive Compulsive Disorder

The purpose of this study is to evaluate the efficacy of troriluzole as adjunctive therapy versus placebo in participants with obsessive compulsive disorder (OCD) who had an inadequate response to selective serotonin reuptake inhibitor (SSRI), clomipramine, venlafaxine, or desvenlafaxine treatment

Inclusion Criteria:

1. Primary diagnosis of OCD as per the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5).

2. Participants must be currently experiencing non-response or inadequate response to their current standard of care (SOC) medication defined as:

   1. Participant Yale-Brown Obsessive Compulsive Scale total score must be ≥ 19 at screening and Baseline, reflecting moderate or severe OCD symptoms.
   2. Participants must currently be on a SSRI, clomipramine, venlafaxine or desvenlafaxine.

3. Determined by the investigator to be medically stable at baseline/randomization as assessed by medical history, physical examination, laboratory test results, and electrocardiogram testing. Participants must be physically able and expected to complete the trial as designed;

4. Minimum of 6 years of education or equivalent and sufficiently fluent in English to complete necessary scales and understand consent forms;

5. Participants must have adequate hearing, vision, and language skills to perform neuropsychiatric testing and interviews as specified in the protocol;

6. Participants must be able to understand and agree to comply with the prescribed dosage regimens and procedures; report for regularly scheduled office visits; and reliably communicate with study personnel about adverse events and concomitant medications;

7. It is required that all women of child-bearing potential (WOCBP) who are sexually active agree to use two methods of contraception for the duration of the study (i.e. beginning 30 days prior to baseline and extending to 30 days after the last dose of study drug).

8. WOCBP must have a negative serum pregnancy test at screening and a negative urine pregnancy test prior to dosing at Baseline;

9. It is required that men who are sexually active with WOCBP agree to use 2 methods of contraception for the duration of the study (beginning at first treatment and extending to 90 days after the last dose of study drug).

10. The duration of the subject's OCD disease was to be ≥ 1 year.

11. In addition, subjects had to be on stable doses of other psychotropic medication for at least 12 weeks prior to screening.

12. Subjects had to have a Clinical Global Impression of Severity Scale (CGI-S) score of ≥ 4 at screening and baseline.

Exclusion Criteria:

1. Participants should be excluded with a history of more than 2 previous failed treatment trials of SSRIs, clomipramine, venlafaxine, or desvenlafaxine (not including the current SSRI trial) given for an adequate duration at an adequate dose as defined by the following criteria taken from the Massachusetts General Hospital Treatment Response Questionnaire for OCD (MGH-TRQ-OCD) as follows:

   1. Treatment failure / non-response: As per the MGH-TRQ-OCD, there has been minimal or no meaningful clinical benefit as perceived by the participant despite an adequate dose and duration of treatment;
   2. Adequate duration: At least 10 weeks of treatment with SSRI, clomipramine, venlafaxine, or desvenlafaxine
   3. Adequate dose: Defined by the the United States Prescribing Information labeling.

2. Evidence at screening or baseline of any medical or psychiatric condition other than OCD that could predominantly explain or contribute significantly to the subjects' symptoms or that could confound assessment of OCD symptoms

3. Mini Mental State Examination (MMSE) score of < 24 at Screening

4. Current or prior history, per DSM-5 criteria, of bipolar I or II disorder, schizophrenia or other psychotic disorders, schizoaffective disorder, autism or autistic spectrum disorders, borderline personality disorder, antisocial personality disorder, body dysmorphic disorder, hoarding disorder (symptoms of hoarding disorder as part of the OCD diagnosis are allowed, but a primary diagnosis of hoarding disorder is excluded); a current diagnosis of Tourette's disorder is also excluded;

5. Any eating disorder within the last 12 months;

6. Acute suicidality or suicide attempt or self-injurious behavior in the last 6 months;

7. History of psychosurgery, Deep Brain Stimulation (DBS) or Electroconvulsive Therapy (ECT).

8. Transcranial Magnetic Stimulation (TMS) is prohibited within 3 months prior to screening and during the study.

9. Participants who may have received a non-biological investigational agent in any clinical trial within 30 days, or a biological agent within 90 days prior to screening are excluded.

10. Creatinine ≥ 2 mg/dL.

11. Course of treatment for participants with localized cancers (without metastatic spread) is 5 years prior to screening.

12. QTcF (Fridericia) interval ≥ 470 msec during the screening or baseline period or uncontrolled arrhythmia or frequent premature ventricular contraction (PVCs) (> 5/minute) or Mobitz Type II second or third degree atrioventricular (AV) block or left bundle branch block, or right bundle branch block with a QRS duration ≥ 150 msec or intraventricular conduction defect with a QRS duration ≥150 msec or evidence of acute or sub-acute myocardial infarction or ischemia and added or other electrocardiogram findings that, in the investigator's opinion, would preclude participation in the study.

13. Previous treatment with riluzole