BPL-003 Efficacy and Safety in Treatment Resistant Depression

Study Overview
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Brief Summary
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This is a Phase 2 study randomized, quadruple masked, multi-center study designed to investigate the efficacy and safety of a single dose of BPL-003 combined with psychological support in patients with treatment resistant depression (TRD).

Detailed Description
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Approximately 225 eligible participants will be receive a single dose of either low, medium, or high doses BPL-003, given intranasally, with 8 weeks of follow-up assessments. Psychological support will be given before, during and after dosing.

Official Title
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A Quadruple Masked, Dose-Finding Study to Evaluate the Efficacy and Safety of Intranasal BPL-003 in Patients With Treatment Resistant Depression

Conditions
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Treatment Resistant Depression

Intervention / Treatment
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* Drug: BPL-003


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least moderate major depressive disorder. Diagnosed with TRD defined as failure to respond to an adequate dose and duration of at least 2 pharmacological treatments based on the MGH ATRQ assessment. Hamilton Depression Rating Scale score ≥19 at Screening and Baseline. CGI-S ≥4 at Screening and Baseline. If currently taking antidepressant medications, willing and able to discontinue current antidepressants. Exclusion Criteria: Current or past history of schizophrenia, psychotic disorder including psychotic depression, bipolar disorder, delusional disorder, schizoaffective disorder, or any other severe psychiatric disorder. Current personality disorders. First-degree family history of schizophrenia, bipolar disorder, delusional disorder, or schizoaffective disorder. Current alcohol or substance use disorder (other than caffeine or nicotine). A participant who at any time has been unresponsive to ketamine, esketamine, an adequate course of treatment with electroconvulsive therapy, or has received vagal nerve stimulation or deep brain stimulation. Suicidal ideation or behavior within the 12 months prior to the start of Screening or on Day 1 prior to dosing. Suicide attempt and/or self-injurious behavior within the last 12 months prior to Screening. Uncontrolled medical conditions e.g. hypo/hyperthyroidism, diabetes, renal failure. History or current uncontrolled hypertension. Seizure disorder or any seizure in the 2 years prior to Screening. Has clinically significant results on ECG during the Screening. Any nasal obstruction, blockage, or symptoms of congestion at the time of dosing that in the investigator's opinion may interfere with the administration of the study medication. Female participants who are pregnant, lactating, or of childbearing potential and not willing to use adequate forms of contraception during the study. Male participants who are sexually active and not willing to use adequate forms of contraception during the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low dose<br>Active placebo comparator | Drug: BPL-003<br>* A single dose administered intranasally<br>|
| Experimental: Medium dose<br> | Drug: BPL-003<br>* A single dose administered intranasally<br>|
| Experimental: High dose<br> | Drug: BPL-003<br>* A single dose administered intranasally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) | High compared to low dose of BPL-003. The MADRS is a 10-item diagnostic questionnaire used to measure the severity of depressive episodes in participants with mood disorders. A higher MADRS score indicates more severe depression, and each item yields a score of 0-6. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) | High compared to low dose of BPL-003. The MADRS is a 10-item diagnostic questionnaire used to measure the severity of depressive episodes in participants with mood disorders. A higher MADRS score indicates more severe depression, and each item yields a score of 0-6. | 1 week | 
| Change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) | Medium compared to low dose of BPL-003. The MADRS is a 10-item diagnostic questionnaire used to measure the severity of depressive episodes in participants with mood disorders. A higher MADRS score indicates more severe depression, and each item yields a score of 0-6. | 4 weeks and 1 week | 
| Safety of BPL-003 given with psychological support as assessed by number and percentage of participants with adverse events |  | 8 weeks | 
| Safety of BPL-003 given with psychological support as assessed by percentage of participants with clinically significant abnormal laboratory tests |  | 8 weeks | 
| Safety of BPL-003 given with psychological support as assessed by percentage of participants with clinically significant abnormal vital sign measurements |  | 8 weeks | 
| Safety of BPL-003 given with psychological support as assessed by percentage of participants with clinically significant ECG parameters compared |  | 8 weeks | 
| Safety of BPL-003 given with psychological support as assessed by incidence of suicidal ideation or behavior |  | 8 weeks | 
| Plasma levels of 5-MeO-DMT and its metabolites |  | 1 day |