Study to Evaluate the Efficacy and Safety of Intranasal BPL-003 in Patients with Treatment Resistant Depression

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Beckley Psytech Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

8 Sep 2023 → 4 Jul 2025

Decision date (initial)

2024-09-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Beckley Psytech Ltd.

External identifiers

EU CT number

2024-513457-70-00

EudraCT number

2022-003743-10

ClinicalTrials.gov

NCT05870540

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Dose response, Safety, Efficacy, Therapy

CORE study: To determine the efficacy of [CCI] mg of BPL-003 given with psychological support to participants with treatment--resistant depression (TRD)

Open label extension (OLE): To determine the safety of [CCI] BPL-003 given with psychological support to participants with TRD

Secondary objectives 7

1. CORE: To determine the efficacy, including early onset, of BPL-003 given with psychological support to participants with TRD
2. CORE: To determine the safety of [CCI] mg, [CCI] mg, or [CCI] mg of BPL-003 given with psychological support to participants with TRD
3. CORE: To evaluate the pharmacokinetics (PK) of 5-methoxy-N,Ndimethyltryptamine (5-MeO-DMT) and its metabolites (including bufotenine) in participants with TRD after nasal administration of BPL- 003
4. CORE: To determine the effects on depression and disability of [CCI] mg, [CCI] mg, or [CCI] mg of BPL-003 given with psychological support to participants with TRD
5. OLE: To determine the efficacy of [CCI] BPL-003 given with psychological support to participants with TRD
6. OLE: To evaluate the PK of 5-MeO-DMT and its metabolites (including bufotenine) in participants with TRD after nasal administration of BPL- 003
7. OLE: To determine the effects of [CCI] BPL-003 on depression & disability, given with psychological support to participants with TRD

Conditions and MedDRA coding

Treatment-Resistant Depression (TRD)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. 1. Willing and able to give informed consent, with written informed consent available before any study assessments.
2. 2. Male and female participants, age 18 to 75 years at the time of informed consent.
3. 3. At least moderate major depressive disorder (MDD), (single or recurrent episode as informed by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [DSM-5] criteria; if single episode, duration of ≥3 months and ≤ 2 years) based on medical records, clinical assessment, and documented completion of the version 7.0.2 Mini International Neuropsychiatric Interview (MINI). For clarification, if recurrent MDD, there is no limit on episode duration.
4. 4. Diagnosed with TRD defined as failure to respond to an adequate dose and duration of at least 2 pharmacological treatments, in the current episode, based on the MGH ATRQ assessment. Augmentation with an add-on treatment counts as a second treatment. Participants must not have failed more than 5 prior pharmacological treatments current episode (psychotherapy is not counted towards treatment failure). For clarification, pharmacological treatments initially effective but subsequently ineffective (tachyphylaxis) will be considered treatment failures if they fulfil the ATRQ criteria for dose and duration of failure.
5. 5. Hamilton Depression Rating Scale (HDRS) (17 item) score ≥19 at Screening (Visit 1) and baseline (Day -3).
6. 6. CGI-S ≥4 at Screening and baseline (Day -3).
7. 7. If currently taking antidepressant medications, willing and able to discontinue current antidepressants including selective serotonin reuptake inhibitor, serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors, and any augmentation medication such as antipsychotics or lithium. Withdrawal will follow local treatment guidelines and should aim to avoid withdrawal symptoms by gradually reducing the antidepressant treatment dose.
8. 8. Able (in the investigator's opinion) and willing to undertake and comply with all study requirements, including ability to complete all protocol required assessment tools and to comply with all study visits in language used by study site.
9. 9. Willing to abstain from alcohol for 48 hours before [CCI].
10. 10. Willing to abstain from recreational drugs from Screening until the end of the study. • Intermittent use of cannabinoids prior to Screening is not exclusionary as long as the participant does not meet the criteria for substance use disorder, as assessed using the DSM-5.
11. 11. Willing to allow their own general practitioner, and consultant if appropriate, to be informed of study participation.
12. OLE: 1. Participants who complete the CORE study.
13. OLE: 2. Willing and able to give informed consent for the OLE.
14. OLE: 3. Willing to abstain from alcohol for 48 hours before OLE [CCI].
15. OLE: 4. Willing to abstain from recreational drugs throughout the duration of the study.

Exclusion criteria 18

1. 1. Use of cannabinoids is not allowed for the duration of the study. Participants should not be administered the study drug if they have a positive urine drug screen result for cannabinoids pre-dose on [CCI] (retesting is allowed if there is a suspected false positive test).
2. 2. Current or past history of schizophrenia, post-traumatic stress disorder, psychotic disorder including psychotic depression, bipolar disorder, delusional disorder, schizoaffective disorder, or any other severe psychiatric disorder as assessed by medical history and a structured clinical interview (MINI).
3. 3. Current personality disorders: Cluster A (paranoid, schizoid, schizotypal), Cluster B (antisocial, borderline, histrionic, narcissistic), or Cluster C (avoidant, dependent, -obsessive compulsive) assessed via McLean Screening Instrument for Borderline Personality Disorder (MSIBPD), MINI, and clinical judgement.
4. 4. First-degree family history of schizophrenia, bipolar disorder, delusional disorder, or schizoaffective disorder.
5. 5. Current (within the last year) alcohol or substance use disorder (other than caffeine or nicotine) according to DSM-5 and assessed by the MINI at Screening that in the opinion of the investigator will be a safety concern for enrollment in the study or that could interfere with the therapeutic process or with other aspects of study participation. Any participant who is not able to agree or adhere to a plan to reduce and manage use will be excluded.
6. 6. A participant who at any time has been unresponsive to ketamine or esketamine, unresponsive to an adequate course of treatment with electroconvulsive therapy (ECT) defined as at least 7 treatments with unilateral/bilateral ECT, or has received vagal nerve stimulation or has received deep brain stimulation.
7. 7. Currently receiving prohibited medications or therapy.
8. 8. Suicidal ideation with some intent to act within 12 months prior to the start of Screening, per the investigator's clinical judgement or based on the C-SSRS, corresponding to a response of "Yes" on Item 4 (active suicidal ideation with some intent to act, without specific plan) or Item 5 (active suicidal ideation with specific plan and intent) for suicidal ideation on the C-SSRS, or any suicidal behavior within the 12 months prior to the start of Screening. Participants reporting suicidal ideation with intent to act or suicidal behavior as assessed on [CCI] should be excluded.
9. 9. Suicide attempt and/or self-injurious behavior within the last 12 months prior to Screening.
10. 10. Depression is secondary to other severe medical conditions according to the investigator's opinion.
11. 11. Other personal circumstances and behavior judged to be incompatible with establishment of rapport or safe exposure to the study medication.
12. 12. Any other clinically significant psychiatric condition that, in the opinion of the investigator, may interfere with the interpretation of the study results or constitute a health risk for the participant if he/she takes part in the study.
13. OLE: 1. Currently taking antidepressant medication.
14. OLE: 2. Currently taking any other prohibited medication.
15. OLE: 3. Participants who, in the opinion of the investigator, are not suitable to participate in the OLE.
16. OLE: 4. Participants who met the Subject Dosing Stopping Criteria in the CORE
17. OLE: 5. Participants with controlled hypertension on antihypertensive therapy are excluded if repeated clinic seated or semi-recumbent systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥ 80 mmHg. Participants without a diagnosis of hypertension are excluded if repeated clinic seated or semi-recumbent systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg. Blood pressure eligibility should be assessed during Screening and predose on [CCI].
18. OLE: 6. Participants where the CORE dose was not well tolerated.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 6

1. CORE: Change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) for [CCI] mg compared to [CCI] mg of BPL-003 at [CCI]
2. OLE: • Number of events and percentage of participants with TEAEs
3. OLE: • Percentage of participants with clinically significant abnormal laboratory tests compared to OLE and CORE baseline
4. OLE: • Percentage of participants with clinically significant abnormal vital sign measurements (heart rate, blood pressure, and body temperature) compared to OLE and CORE baseline
5. OLE: • Percentage of participants with clinically significant ECG parameters compared to OLE and CORE baseline
6. OLE: • Incidence of suicidal ideation or behavior, as assessed by the C-SSRS compared to OLE and CORE baseline

Secondary endpoints 25

1. 1. Change from baseline in MADRS for [CCI] mg compared to [CCI] mg of BPL- 003 at [CCI]
2. 2. Change from baseline in MADRS for [CCI] mg compared to [CCI] mg of BPL- 003 at [CCI]
3. 3. Change from baseline in MADRS for [CCI] mg compared to [CCI] mg of BPL- 003 at [CCI]
4. 4. Number of events and percentage of participants with treatment - emergent adverse events (TEAEs)
5. 5. Percentage of participants with clinically significant abnormal laboratory tests compared to baseline
6. 6. Percentage of participants with clinically significant abnormal vital sign measurements (heart rate, blood pressure, and body temperature) compared to baseline
7. 7. Percentage of participants with clinically significant electrocardiogram (ECG) parameters compared to baseline
8. 8. Incidence of suicidal ideation or behavior, as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) at [CCI] compared to baseline
9. 9. Impairment in cognitive performance, assessed by Cognitive Test Battery at [CCI] compared to baseline
10. 10. Plasma levels of 5-MeO-DMT and its metabolites (including bufotenine) up to [CCI] after nasal administration of BPL-003
11. 11. Change from baseline in MADRS for [CCI] mg and [CCI] mg of BPL-003 compared to [CCI] mg of BPL-003 at [CCI]
12. 12. Percentage of responders (defined as 50% reduction in MADRS total score) at [CCI] compared to baseline, by dose group
13. 13. Percentage of participants in remission (defined as MADRS total score ≤ 10) at [CCI] by dose group
14. 14. Change in 16-item Quick Inventory of Depressive Symptomatology- Self-Report (QIDS-SR-16) score at [CCI] compared to baseline, by dose group
15. 15. Change in Quality of Life in Depression Scale (QLDS) score at [CCI] compared to baseline, by dose group
16. 16. Change in Sheehan Disability Scale (SDS) total score at [CCI] compared to baseline, by dose group
17. 17. Change in Clinical Global Impression-Severity (CGI-S) score at [CCI] compared to baseline, by dose group
18. OLE: 1. Change in MADRS compared to OLE and CORE baseline
19. OLE: 2. Percentage of responders (defined as 50% reduction in MADRS total score) compared to OLE and CORE baseline
20. OLE: 3. Percentage of participants in remission (defined as MADRS total score ≤ 10) compared to OLE and CORE baseline
21. OLE: 4. Plasma levels of 5-MeO-DMT and its metabolites (including bufotenine) up to [CCI] after nasal administration of BPL-003
22. OLE: 5. Change in QIDS-SR-16 score compared to OLE and CORE baseline
23. OLE: 6. Change in QLDS score compared to OLE and CORE baseline
24. OLE: 7. Change in SDS total score compared to OLE and CORE baseline
25. OLE: 8. Change in CGI-S score compared to OLE and CORE baseline

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Beckley Psytech Limited

Sponsor organisation

Beckley Psytech Limited

Address

Beckley Park Farm, Beckley Beckley

City

Oxford

Postcode

OX3 9SY

Country

United Kingdom

Scientific contact point

Organisation

Beckley Psytech Limited

Contact name

Associate Director, Clinical Science

Public contact point

Organisation

Beckley Psytech Limited

Contact name

Clinical Trial Information

Third parties 13

Locations

3 EU/EEA countries · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 26 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications