Clinical TrialMajor Depressive Disorder (MDD)PsilocybinPsilocybinPlaceboCompleted

A dose-finding and proof-of-concept study of the efficacy and safety of MSP-1014.OX in patients with major depressive disorder

Adaptive Phase IIa/IIb study (n=70) with open-label dose-finding (30/50/70 mg oral MSP-1014.OX) followed by a double-blind, randomised, placebo-controlled proof-of-concept single-dose study with preparatory and integration psychotherapy in MDD patients with partial/no SSRI response.

Target Enrollment
70 participants
Study Type
Phase II interventional
Design
Randomized, double Blind

Detailed Description

Part 1 is an open-label, multiple-ascending-dose, dose-finding study (30, 50, 70 mg oral MSP-1014.OX, three doses four weeks apart) to assess safety, cardiovascular effects, pharmacokinetics and pharmacodynamics in ~10 patients.

Part 2 is a double-blind, randomised (1:1) placebo-controlled proof-of-concept study of the selected dose with single dosing; all participants receive preparatory psychotherapy (3 sessions) and integration therapy (three sessions for Part 2).

Primary outcomes: Part 1 safety signals and cardiovascular parameters (HR, BP, QTc); Part 2 efficacy on MADRS at 4 weeks. Secondary outcomes include pharmacokinetics (psilocin plasma), subjective intensity, cognitive and biomarker measures (BDNF), and quality-of-life metrics.

Study Protocol

Preparation

3 sessions

Dosing

sessions

Integration

3 sessions

Therapeutic Protocol

Manualized psychotherapy included

Study Arms & Interventions

Dose-finding

experimental

Part 1 open-label: oral MSP-1014.OX 30, 50 and 70 mg; multiple-ascending-dose, three doses four weeks apart

Interventions

  • Psilocybin30 - 70 mg
    via Oral• 3 doses, 4 weeks apart• 3 doses total

    Open-label dose escalation; planned n=10 for Part 1

MSP-1014.OX

experimental

Part 2 double-blind, randomised, placebo-controlled: selected MSP-1014.OX dose (from Part 1) administered as single dosing with psychotherapy

Interventions

  • Psilocybin
    via Oral• single dose

    Selected dose (30/50/70 mg determined in Part 1); Part 2 randomised 1:1; approx. 60 participants (may increase to 82 after interim)

Placebo

inactive

Matched oral placebo for Part 2

Interventions

  • Placebo
    via Oral• single dose

    Placebo comparator, 1:1 allocation in Part 2

Participants

Ages
18 – 99
Sexes
Male & Female

Inclusion Criteria

  • 1. Aged 18 years and above
  • 2. Male or female
  • 3. DSM-5 defined MDD with partial response to SSRI monotherapy (HAM-D score >17) or no response
  • 4. Able to communicate well in English and follow study procedures
  • 5. Any history of suicide attempts/suicidal ideation; the subject scores 'yes' on item 4 or 5 of the Suicidal Ideation section of the Columbia Suicidality Scale scoring if this ideation occurred in the past 12 months, or 'yes' on any item of the Suicidal Behaviour section, and the opinion of the investigator
  • 6. Medically suitable as determined by screening including interview, medical questionnaire, physical exam, ECG and blood tests
  • 7. Currently taking a first course of SSRI antidepressant treatment for at least 8 weeks

Exclusion Criteria

  • 1. Treatment with any other antidepressant medication other than the currently prescribed SSRI antidepressant
  • 2. Current or past diagnosis of schizophrenia, psychotic disorder, bipolar disorder I and II, delusional disorder, paranoid personality disorder, schizoaffective disorder, borderline personality disorder, or judged to be incompatible with establishment of rapport or safe exposure to psilocin, as assessed through medical history and the MINI
  • 3. Family history of schizophrenia, schizoaffective disorder, or bipolar affective disorder
  • 4. Anyone on a research study of an investigational drug or who has been on a clinical trial within 1 month of enrollment
  • 5. Scores from the screener and baseline Columbia Suicide Severity Rating Scale (C-SSRS) that indicate that the participant is of clinically significant risk of suicide; judged to be of high suicide or self-harm risk following psychological assessment at screening or baseline
  • 6. Currently receiving psychotherapy other than that which forms part of this study
  • 7. Current (<1 year) alcohol or drug abuse identified as moderate or severe during screening in accordance with ICD-11 criteria (MINI 7.0.2)
  • 8. Any other reason that might compromise safe exposure to psilocin and the development of a therapeutic relationship necessary for psychological support
  • 9. Previous use of psychedelics in lifetime
  • Medical exclusion criteria:
  • 1. Females who are pregnant, breastfeeding or of childbearing potential unwilling or unable to use effective contraception for study duration
  • 2. Diagnosis of epilepsy or significant seizure risk
  • 3. Cardiovascular conditions including stroke (<1 year), myocardial infarction (<1 year), uncontrolled hypertension (BP >140/90 mmHg) or clinically significant arrhythmia within 1 year
  • 4. Clinically significant findings on physical exam or vital signs (HR <60 or >100 bpm, BP <90/60 or >140/90), ECG abnormalities (QTc), or positive alcohol breath test
  • 5. eGFR <45 ml/min/1.73 m²
  • 6. Liver function tests above specified thresholds
  • 7. Any clinically significant renal, pulmonary, gastrointestinal, hepatic or other illness affecting safety or data interpretation
  • 8. BMI below 16 or above 35 kg/m²
  • 9. Positive urine drug test for psychoactive substances at screening or dosing visit
  • 10. Organic brain injury or diagnosed cognitive impairment

Study Details

Locations

Clerkenwell Health trial unit — London, United Kingdom

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