Open-label Safety Trial of PH94B in Social Anxiety Disorder (SAD)

Study Overview
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Brief Summary
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This study evaluates the safety and tolerability of PH94B with repeated dosing over a period of up to 12 months. Participating subjects will use PH94B up to 4 times a day when they encounter anxiety-provoking situations in daily life. Safety and tolerability of PH94B (≤ 4 doses per day up to 12 months) will be assessed and summarized during monthly visits from baseline (Visit 2) to end of treatment (Visit 14) in AEs, laboratory values, 12-lead ECGs, physical examinations, and vital sign assessments following exposure to PH94B.

Official Title
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A Phase 3 Open-label Safety Trial of PH94B Nasal Spray in the Acute Treatment of Anxiety in Adult Subjects With Social Anxiety Disorder (SAD)

Conditions
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Social Anxiety Disorder

Intervention / Treatment
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* Drug: PH94B


Participation Criteria
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Eligibility Criteria
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Most but not all patients will enter the study following completion of Palisade-1 (NCT047548020) and Palisade-2 (NCT05011396). Inclusion Criteria: Male and female adults, 18 through 65 years of age, inclusive. Women of childbearing potential must be able to commit to the consistent and correct use of an effective method of birth control throughout the study, and must also have a negative urine pregnancy test result at both Screening (Visit 1) (for subjects who attend Visit 1) and Baseline (Visit 2), prior to IP administration. Effective methods of contraception include: condoms with spermicide, diaphragm with spermicide, hormonal contraceptive agents (oral, transdermal, or injectable), or implantable contraceptive devices. Current diagnosis of social anxiety disorder Clinician-rated HAM-D17 total score < 18 at study entry LSAS score 50 or greater Exclusion Criteria: Any history of bipolar disorder (I or II), schizophrenia, schizoaffective disorder, psychosis, anorexia or bulimia, autism-spectrum disorder, or obsessive-compulsive disorder. Any other current Axis I disorder, other than SAD, which is the primary focus of treatment. Note that subjects with concurrent Generalized Anxiety Disorder are eligible for the study provided that Generalized Anxiety Disorder is not the primary diagnosis. Subjects who meet criteria for moderate or severe alcohol or substance use disorder within the 1 year prior to study entry. In the opinion of the Investigator, the subject has a significant risk for suicidal behavior during the course of their participation in the study. Clinically significant nasal pathology or history of significant nasal trauma, nasal surgery, total anosmia, or nasal septum perforation that may have damaged the nasal chemosensory epithelium. An acute or chronic condition, including an infectious illness, uncontrolled seasonal allergies at the time of the study, or significant nasal congestion that potentially could affect drug delivery to the nasal chemosensory epithelium. Subjects using the following psychotropic medications: anticonvulsants, mood stabilizers, antipsychotic medications, gabapentin, pregabalin, opioids, naltrexone, esketamine, and ketamine at enrollment. Subjects using lower doses of atypical antipsychotics at Screening may be eligible after discussion with the Medical Monitor (e.g., quetiapine < 100 mg). In general, subjects using antidepressants or buspirone can continue to receive these provided that they have been taking them for a minimum of 2 months, and have been on a stable dose for a minimum of 1 month. Use of anxiolytics, such as benzodiazepines or unapproved treatments such as beta blockers, within 30 days before study entry; concomitant use is prohibited during the study. Subjects who have been taking benzodiazepines daily for 1 month or longer at the time of Visit 1 are not eligible to participate. Use of any over-the-counter product, prescription product, or herbal preparation for treatment of the symptoms of anxiety or social anxiety within 30 days before study entry; concomitant use is prohibited during the study. Subjects with clinically significant abnormalities in hematology, blood chemistry, urinalysis, 12-lead ECG, or physical examination identified at the Screening visit or Baseline visit that in the clinical judgment of the Investigator, could place the subject at undue risk, interfere with study participation, or confound the results of the study. -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PH94B 3.2 micrograms<br>100 microliter nasal spray to each nostril up to four times a day as needed for acute anxiety | Drug: PH94B<br>* Nasal spray<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events and other safety measures | The primary outcome variable for the study is the change from Baseline (Visit 2) in AEs after the administration of PH94B prior to anxiety-provoking situations in daily life for subjects with SAD. | 12 months | 
| Liebowitz Social Anxiety Scale | Assessment of symptomatology of social anxiety disorder severity | 12 months |