BPL-003 Efficacy and Safety in Treatment Resistant Depression

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

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

Study Overview

• Status: Completed
• Conditions: Treatment Resistant Depression
• Intervention / Treatment: Drug: BPL-003; Drug: BPL-003

Detailed Description

Approximately 200 eligible participants will receive a single dose of either low, medium, or high doses of BPL-003, given intranasally, with 8 weeks of follow up assessments. Following this participants may receive a second dose of either monophasic or biphasic dose of BPL-003, given intranasally, with another 8 weeks of follow up assessments.

Psychological support will be given before, during and after each dosing.

• Study Type: Interventional
• Enrollment (Actual): 196
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Melbourne, Australia, 3053
    • Neurocentrix Research
  • Parkville, Australia, 3050
    • Royal Melbourne Hospital, University of Melbourne
  • New South Wales
    • Sydney, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Dept. of Psychiatry and School Psychological Sciences, Monash University
• Germany
  • Berlin, Germany, 10117
    • Charité - Universitätsmedizin Berlin
  • Berlin, Germany, 10247
    • OVID Clinic, Augmented Psychotherapy
  • Frankfurt am Main, Germany, 60528
    • Department of Psychiatry, University Hospital Frankfurt
  • Mannheim, Germany, 68159
    • Central Institute of Mental Health, Dept. of Molecular Neuroimaging
  • Tubingen, Germany, 72076
    • Universitätsklinik für Psychiatrie und Psychotherapie, Calwerstr. 14
• Poland
  • Gdansk, Poland, 80-546
    • Centrum Badan Klinicznych PI-House sp. z o.o.
  • Gdansk, Poland, 80-214
    • Department of Psychiatry, UCK
  • Lodz, Poland, 92-216
    • SPZOZ Centralny Szpital Kliniczny Uniwersytetu Medycznego w Lodzi
  • Tuszyn, Poland, 95-080
    • Klinika Inventiva
  • Warsaw, Poland, 02-957
    • Department of Pharmacology and Physiology of CNS
• Spain
  • Barcelona, Spain, 08003
    • Hospital Del Mar
  • Barcelona, Spain, 08029
    • Parc Sanitari Sant Joan de Deu HD Numancia
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona, Psychiatry and Psychology Dept.
  • Madrid, Spain, 28050
    • Fundación de Investigación HM Hospital
  • Oviedo, Spain, 33011
    • Centro de Salud Mental La Corredoria
  • Salamanca, Spain, 37005
    • Centro Salud San Juan
• United Kingdom
  • Exeter, United Kingdom, EX2 5DW
    • NIHR Exeter Clinical Research Facility
  • London, United Kingdom, W1G 8DR
    • Clerkenwell Health
  • London, United Kingdom, SE5 8AF
    • King's College London - Institute of Psychiatry, Psychology & Neuroscience (IoPPN) - Centre for Affective Disorders (CfAD)
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • UAB School of Public Health, Department of Health Behavior
  • Arkansas
    • Rogers, Arkansas, United States, 72758
      • Woodland Research Northwest
  • California
    • San Diego, California, United States, 92037
      • Kadima Neuropsychiatry Institute
    • San Francisco, California, United States, 94114
      • San Francisco Insight and Integration Center
    • Santa Monica, California, United States, 90404
      • Pacific Neuroscience Institute, Treatment and Research in Psychedelics (TRIP) Program
  • Colorado
    • Fort Collins, Colorado, United States, 80525
      • Wholeness Center
  • Florida
    • Lauderhill, Florida, United States, 33319
      • Segal Trials Center for Psychedelic and Cannabis Research
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • CenExel ACMR
    • Atlanta, Georgia, United States, 30329
      • Emory University, Brain Health Center, Department of Psychiatry and Behavioral Sciences
    • Decatur, Georgia, United States, 30030
      • CenExel iResearch
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Sunstone Medical PC (Sunstone Therapies / Aquilino Cancer Center)
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Boston Clinical Trials
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • CenExel HRI
  • New York
    • New York, New York, United States, 10032
      • New York State Psychiatric Institute
  • Oregon
    • Portland, Oregon, United States, 97227
      • Portland Psychotherapy
  • Texas
    • DeSoto, Texas, United States, 75115
      • InSite Clinical Research
    • Plano, Texas, United States, 75093
      • AIM Trials
  • Utah
    • Draper, Utah, United States, 84020
      • Cedar Clinical Research
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin, Dept of Family Medicine & Community Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. At least moderate major depressive disorder.
2. 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.
3. Hamilton Depression Rating Scale score ≥19 at Screening and Baseline.
4. CGI-S ≥4 at Screening and Baseline.
5. If currently taking antidepressant medications, willing and able to discontinue current antidepressants.

Exclusion Criteria:

1. Current or past 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, 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 or behavior within the 12 months prior to the start of Screening or on Day 1 prior to dosing.
7. Suicide attempt and/or self-injurious behavior within the last 12 months prior to Screening.
8. Uncontrolled medical conditions e.g. hypo/hyperthyroidism, diabetes, renal failure.
9. History or current uncontrolled hypertension.
10. Seizure disorder or any seizure in the 2 years prior to Screening.
11. Has clinically significant results on ECG during the Screening.
12. 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.
13. Female participants who are pregnant, lactating, or of childbearing potential and not willing to use adequate forms of contraception during the study.
14. Male participants who are sexually active and not willing to use adequate forms of contraception during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High dose	Drug: BPL-003; A single dose administered intranasally; Drug: BPL-003; A single dose administered intranasally (administered as 2 nasal sprays minutes apart)
Experimental: Medium dose	Drug: BPL-003; A single dose administered intranasally; Drug: BPL-003; A single dose administered intranasally (administered as 2 nasal sprays minutes apart)
Experimental: Low dose; Active placebo comparator	Drug: BPL-003; A single dose administered intranasally; Drug: BPL-003; A single dose administered intranasally (administered as 2 nasal sprays minutes apart)
Experimental: Monophasic	Drug: BPL-003; A single dose administered intranasally; Drug: BPL-003; A single dose administered intranasally (administered as 2 nasal sprays minutes apart)
Experimental: Biphasic	Drug: BPL-003; A single dose administered intranasally; Drug: BPL-003; A single dose administered intranasally (administered as 2 nasal sprays minutes apart)

What is the study measuring?

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
OLE Primary Safety Outcome Measure	To determine the safety of a second dose of BPL-003 given with psychological support to participants with TRD as assessed by treatment-emergent adverse events.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Beckley Psytech Limited
• Investigators: Study Director: VP & Head of Clinical Development, Beckley Psytech Ltd

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2023
• Primary Completion (Actual): March 28, 2025
• Study Completion (Actual): July 3, 2025

Study Registration Dates

• First Submitted: May 12, 2023
• First Submitted That Met QC Criteria: May 12, 2023
• First Posted (Actual): May 23, 2023

Study Record Updates

• Last Update Posted (Actual): July 18, 2025
• Last Update Submitted That Met QC Criteria: July 17, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant
• Other Study ID Numbers: BPL-003-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Due to the GDPR, individual participant data will not be shared publicly. Group data will be presented in publication after study completion

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No