Evaluation of Psilocybin-Assisted Psychotherapy in Treating Severe Depression in Patients With PTSD

NCT06141876 | Unknown Phase 2

• 1 other identifier: APEX-002-A02-01
• Study Type: interventional
• Target: 160
• Locations: 0 countries
• Sites: N/A

Brief Summary

Post-Traumatic Stress Disorder (PTSD) is a mental disorder that may develop in people who have been exposed to a traumatic event, including actual or threatened death, serious injury, or sexual violence. Exposure to a traumatic event is defined as directly experiencing the event, learning about the event, or repeated exposure to details of the event. PTSD is often accompanied by other psychiatric and physical comorbidities, both of which are associated with elevated healthcare costs. Depression, psychosis and suicide rates are consistently reported in greater proportion of PTSD patients. Despite the overwhelming impact of PTSD and comorbid depression, there is a shortfall of effective treatments with few side effects that target the broad range of symptoms, including depression. Psilocybin has been studied for the treatment of depression, anxiety, tobacco and alcohol use disorders, obsessive-compulsive disorder, end of life depression and anxiety, demonstrating safety and efficacy for a variety of indications, with no significant adverse events occurring during the course of treatment and follow-up. Notably, in a participant group distinguished by long-standing, moderate to severe major depressive disorder, two doses of psilocybin-assisted therapy were found to be as effective in antidepressant effects as 6 weeks of daily escitalopram, a commonly used SSRI. Promising results found in these studies have led to psilocybin recently receiving breakthrough designation from the US FDA for its potential therapeutic effect in the treatment of depression. Based on previous research, psilocybin has demonstrated a favorable safety profile and has shown preliminary efficacy against depression as well as other symptoms that typically affect patients with PTSD. Unlike traditional SSRIs which are associated with treatment-resistance and addiction, psilocybin requires few doses to improve a wide-range of symptoms and has not been linked with physical dependence. Furthermore, the effect of other psychedelics can vary greatly and may potentially exacerbate existing conditions.

Conditions

Post-traumatic Stress Disorder; Depression

Outcome Measures

Primary Outcomes (3)

• Incidence of adverse events

  Treatment emergent AEs and SAEs

  Baseline to Day 140

• Number of participants with abnormal vital signs, abnormal physical exam findings, abnormal ECG, and abnormal laboratory tests results

  Measurements: vital signs, physical exam, ECG, and laboratory tests

  Baseline to Day 140

• Change in severity of depressive symptoms

  Assessed by total score of Beck Depression Inventory (BDI-II); 21-items scale. Total score of 0-13 is considered minimal range, 14-19 is mild, 20-28 is moderate, and 29-63 is severe.

  Baseline to Day 77

Secondary Outcomes (5)

• Change in severity of depressive symptoms

  Baseline to Days 21, 49, and 140

• Change in severity of PTSD symptoms

  Baseline to Days 21, 49, 77 and 140

• Change in severity of anxiety

  Baseline to Days 21, 49, 77 and 140

• Change in presence and severity of suicidal ideation and behaviour

  Baseline to Days 21, 49, 77 and 140

• Change in chronic pain severity

  Baseline to Days 21, 49, 77 and 140

Study Arms (2)

Active

EXPERIMENTAL

APEX-002-A02

Drug: APEX-002-A02

Placebo

PLACEBO COMPARATOR

matched placebo

Other: Placebo

Interventions

APEX-002-A02 DRUG

Active

Also known as: psilocybin

Active

Placebo OTHER

placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals between 18 and 65 years of age, inclusive, at the time of consent.
• Individuals who are fluent in the language of the study site, specifically English or French.
• Meet DSM-5 criteria for current PTSD with presence of symptoms for at least 6 months at screening.
• Participant must have at least moderate PTSD, as scored as ≥35 on the CAPS-5 scale at screening.
• Participant must have severe depression, as scored as ≥30 on the BDI-II scale at screening.
• If individuals are on psychotropic medications, they must be on stable doses (no dosing adjustments/changes for ≥4 weeks) prior to beginning of the study and for the duration of the study.
• If individuals are users of psychoactive substances, including alcoholic beverages, tobacco, and cannabis, they must remain on stable doses for the duration of the study.
• For individuals of childbearing potential involved in any sexual intercourse that could lead to pregnancy: willing to use adequate birth control to prevent pregnancy (in participant or partner) for the entire duration of the study.
• Capable of providing ongoing, signed informed consent.
• Available for the duration of the study, and able and willing to comply with all study procedures, including completion of questionnaires.
• Agree to identify a local contact person to the research team, that is available over the entire course of the subject's participation in the study to act as an emergency contact.

You may not qualify if:

• Female subject that is pregnant, is planning or suspected to become pregnant, or is lactating.
• Known or suspected hypersensitivity or contraindication to psilocybin or any constituents or excipients of the study drug.
• Abnormal and clinically significant results on the physical examination, vital signs, ECG or laboratory tests at screening.
• Presence of any unstable medical condition or neurological illness, in the opinion of the Investigator.
• History of clinically significant cardiovascular disease including but not limited to stroke, myocardial infarction or clinically significant arrhythmia (in the past 1 year).
• Indication of inadequately treated current hypertension (resting systolic blood pressure \>140 mmHg and/or diastolic blood pressure \>90 mmHg) at screening.
• If a subject is being treated with inhibitor(s) of UGT1A9, UGT1A10, monoamine oxidase (MAO), aldehyde dehydrogenase (ALDH), or alcohol dehydrogenase (ADH) they should be discontinued at least five half lives prior to administration of study drug.
• Lifetime history of psychosis-related disorder or bipolar disorder (I or II).
• Subject has 1st degree relative(s) with schizophrenia or bipolar disorder.
• At the time of screening, any condition other than PTSD judged to be the primary presenting psychiatric diagnosis, in the opinion of the Investigator.
• Clinical diagnosis of dementia or any physical, cognitive, or language impairment of such severity as to adversely affect the validity of the data derived from the patient reported outcomes.
• History of any other clinically significant pulmonary, gastrointestinal, hepatic, renal or any other major concurrent illness 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.
• Individuals who present a current risk to themselves or others, as assessed by the Investigator. This includes, but is not limited to:
• Active suicidal ideation with specific plan and intent in the past 1 month, as assessed with the C-SSRS at screening.
• History of suicidal behavior (actual attempt, interrupted attempt, aborted or self-interrupted attempt, preparatory acts or behavior) in the past 3 months, as assessed with the C-SSRS at screening.

Sponsors & Collaborators

• Apex Labs Ltd.: lead

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Depression

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2023
• First Posted: November 21, 2023
• Study Start: December 15, 2023
• Primary Completion: June 15, 2025
• Study Completion: June 15, 2025
• Last Updated: November 29, 2023

Record last verified: 2023-11