An Open-Label Study to Evaluate the Safety, Tolerability and Pharmacodynamics of BPL-003 in Patients with Treatment Resistant Depression

An open-label, multi-centre, Phase 2a study to evaluate the safety, tolerability, and pharmacodynamics of one and two doses of intranasal BPL-003 combined with psychological support, in patients with treatment resistant depression when administered as monotherapy or as adjunctive therapy with defined SSRIs (citalopram, escitalopram, sertraline or fluoxetine).

Part 1: Up to 32 patients, across 2 parallel arms (Arms A and Arms B) will receive one of two single doses of BPL-003, given intranasally, with 12 weeks of follow-up assessments.

Part 2: Up to 32 patients, across 2 parallel arms (Arms A and Arms B) will receive two doses of BPL-003, given intranasally, with 10 weeks of follow-up assessments.

Psychological support will be given before, during and after dosing in Part 1 and Part 2.

Eligibility Criteria:
Inclusion Criteria:

1. Diagnosed with Major Depressive Disorder.
2. Diagnosed with TRD defined as failure to respond to an adequate dose and duration of at least 2 pharmacological treatments in the past 5 years prior to screening, at least one of which is during the current episode.
3. Montgomery-Asberg Depression Rating Scale score ≥24 at Screening.
4. Clinical Global Impression - Severity ≥4 at Screening.
5. Willing and able to discontinue current pharmacological anti-depressant therapy.
6. On current stable dose of pharmacological antidepressant therapy limited to one of 4 SSRIs (Arm B), i.e. either citalopram, escitalopram, sertraline or fluoxetine.

Exclusion Criteria:

1. Current or history of schizophrenia, psychotic disorder including psychotic depression, bipolar disorder, delusional disorder, schizoaffective disorder, or any other severe psychiatric disorder.
2. Current personality disorders.
3. First-degree family history of schizophrenia, bipolar disorder, delusional disorder, personality disorders or schizoaffective disorder.
4. Current alcohol or substance use disorder (other than caffeine or nicotine).
5. 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.
6. Suicidal ideation with the intent to act or suicidal behaviour within the 12 months prior to the start of Screening or on Day 1 prior to dosing.
7. Suicide attempt and/or self-injurious behaviour within the last 12 months prior to Screening.
8. Uncontrolled medical conditions e.g. hypo/hyperthyroidism, diabetes, renal failure.
9. Seizure disorder or history of seizures (including febrile seizures).
10. Abnormal and clinically significant results on the physical examination, vital signs, electrocardiogram, or laboratory tests at Screening Baseline.
11. Any nasal obstruction, blockage, or symptoms of congestion at the time of dosing, that in the Investigator's opinion may interfere with administration of the study drug.
12. Currently receiving lithium, antipsychotics, serotonergic drugs (excluding the permitted SSRIs for arm B), psychostimulants, or any other prohibited medication.
13. Female patients who are pregnant or lactating, or of childbearing potential and not willing to use adequate forms of contraception.
14. Male patients who are sexually active and not willing to using adequate forms of contraception.