Treatment Resistant Depression
Conditions
Brief summary
This is a Phase 2 study randomized, quadruple-masked, multi-center trial with an open-label extension (OLE), designed to investigate the efficacy and safety of BPL-003 in patients with treatment resistant depression (TRD).
Detailed description
During the main part of the trial, approximately 200 eligible participants will receive a either a low (sub-therapeutic), medium, or high single dose of BPL-003, given intranasally, with 8 weeks of follow-up assessments. Following this, participants may receive a second high dose of BPL-003 during the OLE, given intranasally as either a single spray or two sprays 10 minutes apart, with another 8 weeks of follow-up assessments. Psychological support will be given before, during, and after each dose.
Interventions
DRUGBPL-003
A single dose administered intranasally
Sponsors
Beckley Psytech Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
CORE: Quadruple masking: participant, investigator, outcomes assessor, and sponsor. OLE: Open-label extension.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of TRD. 2. History consistent with TRD. 3. Current depressive episode which is at least moderate in severity (Hamilton Depression Rating Scale score is ≥19 and Clinical Global Impression-Severity score is ≥4). 4. Willing and able to discontinue current antidepressants, if applicable.
Exclusion criteria
1\. Other co-morbidities.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Core: Change From Baseline in Montgomery and Asberg Depression Rating Scale (MADRS) Total Score at Day 29 (12 mg vs 0.3 mg BPL-003) | 4 weeks | The MADRS is a 10-item diagnostic questionnaire used to measure the severity of depressive episodes in participants with mood disorders. The MADRS was administered remotely throughout the trial by independent, centralized, qualified raters. The rater used the SIGMA to interview the participant, moving from broadly based questions about symptoms to more detailed questions that allowed the precise rating of symptom severity. The SIGMA provides structured probes to ensure standardization of administration and comprehensiveness of coverage of the 10 items of the scale. A higher MADRS score indicates more severe depression, with each item yielding a score of 0-6. Total overall scores therefore range from 0-60. The change from baseline in MADRS total score for 12 mg (high dose) vs 0.3 mg (low dose) BPL-003 at Day 29 was assessed. |
| OLE: Number of Participants With Treatment-emergent Adverse Events in the OLE | 8 weeks | The safety of a second dose of BPL-003 given with psychological support to participants with TRD was assessed by the number and percentage of participants with treatment-emergent adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Core: Change From Baseline in MADRS Total Score at Day 8 (12 mg vs 0.3 mg BPL-003) | 1 week | The MADRS is a 10-item diagnostic questionnaire used to measure the severity of depressive episodes in participants with mood disorders. The MADRS was administered remotely throughout the trial by independent, centralized, qualified raters. The rater used the SIGMA to interview the participant, moving from broadly based questions about symptoms to more detailed questions that allowed the precise rating of symptom severity. The SIGMA provides structured probes to ensure standardization of administration and comprehensiveness of coverage of the 10 items of the scale. A higher MADRS score indicates more severe depression, with each item yielding a score of 0-6. Total overall scores therefore range from 0-60. The change from baseline in MADRS total score for 12 mg (high dose) vs 0.3 mg (low dose) BPL-003 at Day 8 was assessed. |
| Core: Change From Baseline in MADRS Total Score at Day 29 (8 mg vs 0.3 mg BPL-003) | 4 weeks | The MADRS is a 10-item diagnostic questionnaire used to measure the severity of depressive episodes in participants with mood disorders. The MADRS was administered remotely throughout the trial by independent, centralized, qualified raters. The rater used the SIGMA to interview the participant, moving from broadly based questions about symptoms to more detailed questions that allowed the precise rating of symptom severity. The SIGMA provides structured probes to ensure standardization of administration and comprehensiveness of coverage of the 10 items of the scale. A higher MADRS score indicates more severe depression, with each item yielding a score of 0-6. Total overall scores therefore range from 0-60. The change from baseline in MADRS total score for 8 mg (medium dose) vs 0.3 mg (low dose) BPL-003 at Day 29 was assessed. |
| Core: Change From Baseline in MADRS Total Score at Day 8 (8 mg vs 0.3 mg BPL-003) | 1 week | The MADRS is a 10-item diagnostic questionnaire used to measure the severity of depressive episodes in participants with mood disorders. The MADRS was administered remotely throughout the trial by independent, centralized, qualified raters. The rater used the SIGMA to interview the participant, moving from broadly based questions about symptoms to more detailed questions that allowed the precise rating of symptom severity. The SIGMA provides structured probes to ensure standardization of administration and comprehensiveness of coverage of the 10 items of the scale. A higher MADRS score indicates more severe depression, with each item yielding a score of 0-6. Total overall scores therefore range from 0-60. The change from baseline in MADRS total score for 8 mg (medium dose) vs 0.3 mg (low dose) BPL-003 at Day 8 was assessed. |
| Core: Number of Participants With Treatment-emergent Adverse Events in the Core Trial Period | 8 weeks | The safety of BPL-003 given with psychological support to participants with TRD was assessed by the number and percentage of participants with treatment-emergent adverse events. Any clinically significant findings during the trial have been included as adverse events. |
Countries
Australia, Germany, Poland, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORKevin Craig, M.D.
Beckley Psytech Ltd
Participant flow
Recruitment details
Participants were recruited to the study between 14-Sep-2023 and 20-Jan-2025.
Pre-assignment details
This trial had 2 periods: a Core trial period followed by an optional OLE trial period. Participants who completed the Core trial period (Core: 0.3, 8, or 12 mg BPL-003 dose groups) had the option to participate in the OLE trial period. During the OLE trial period, eligible participants were randomized in a 1:1 ratio to either monophasic (OLE: 12 mg) or biphasic (OLE: 4 and 8 mg) BPL-003 dosing. In the OLE trial period, randomization was stratified by Core trial period dose group.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous Core trial period | 41.2 Years STANDARD_DEVIATION 10.59 |
| Age, Continuous OLE trial period | 39.6 Years STANDARD_DEVIATION 10.95 |
| Ethnicity (NIH/OMB) Core trial period Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Core trial period Not Hispanic or Latino | 43 Participants |
| Ethnicity (NIH/OMB) Core trial period Unknown or Not Reported | 0 Participants |
| Ethnicity (NIH/OMB) OLE trial period Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) OLE trial period Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) OLE trial period Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) Core trial period American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Core trial period Asian | 3 Participants |
| Race (NIH/OMB) Core trial period Black or African American | 5 Participants |
| Race (NIH/OMB) Core trial period More than one race | 1 Participants |
| Race (NIH/OMB) Core trial period Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Core trial period Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) Core trial period White | 171 Participants |
| Race (NIH/OMB) OLE trial period American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) OLE trial period Asian | 3 Participants |
| Race (NIH/OMB) OLE trial period Black or African American | 3 Participants |
| Race (NIH/OMB) OLE trial period More than one race | 1 Participants |
| Race (NIH/OMB) OLE trial period Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) OLE trial period Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) OLE trial period White | 0 Participants |
| Sex: Female, Male Core trial period Female | 27 Participants |
| Sex: Female, Male Core trial period Male | 30 Participants |
| Sex: Female, Male OLE trial period Female | 0 Participants |
| Sex: Female, Male OLE trial period Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 74 | 0 / 46 | 0 / 73 | 0 / 53 | 0 / 54 |
| other Total, other adverse events | 54 / 74 | 35 / 46 | 62 / 73 | 46 / 53 | 39 / 54 |
| serious Total, serious adverse events | 1 / 74 | 1 / 46 | 0 / 73 | 2 / 53 | 1 / 54 |
Outcome results
None listed