A Phase 3, Randomized, Double-Blind, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of Psilocybin in Adults With Major Depressive Disorder (MDD)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 238
- 试验地点
- 56
- 主要终点
- Change in central rater Montgomery-Asberg Depression Rating Scale (MADRS) total score from Baseline to Trial Day 43
研究概览
简要总结
Approximately 240 eligible adult participants (≥18 years old) who meet Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR) criteria for Major Depressive Disorder (MDD) will be enrolled. Participants will be randomly assigned to receive a single oral dose of Psilocybin 25 mg, Psilocybin 5 mg, or inactive placebo.
The purpose of this study is to evaluate the efficacy, safety, and tolerability of Psilocybin 25 mg versus placebo in adults with MDD, as assessed by the difference between groups in change in depressive symptoms from Baseline to Day 43 post-dose, and to characterize the durability of initial treatment effect and subsequent response to optional Psilocybin 25 mg re-administration(s) during the 1-year Follow-up Period.
详细描述
Double-blind Period:
Participants who show stable depression symptoms between Screening and Trial Baseline will be randomly assigned to receive a single oral dose of Psilocybin 25 mg, Psilocybin 5 mg, or inactive placebo.
Investigational Product (IP) will be administered in the context of a "Set and Setting" (SaS) Protocol for psychosocial support, comprised of 1) a period of preparation with Facilitators prior to dosing; 2) administration of IP in an aesthetically pleasing room under the supervision of two Facilitators; and 3) post-dose integration sessions during which participants will discuss their dosing experience with the Facilitators.
Trial outcome measures will assess depressive symptoms, functional disability, health-related quality of life, and clinical global impression of disease severity.
Long-term Follow-up Period:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
The following roles will be blinded to the treatment group assignment in the Double-blind Period during the trial: Participant, Investigator, Site Personnel, Facilitators, Efficacy Raters (including Site Raters, Participant Raters, and Central Raters), Contract Research Organization (CRO) Staff, and Sponsor.
All roles other than the Sponsor, CRO, and Ethics Committees will also be blinded to the randomization ratio and Patient Health Questionnaire-9 (PHQ-9) score for re-administration eligibility.
The Central MADRS Rater will also be blinded to all aspects of the protocol and trial visit for each participant.
Blinded trial site personnel will complete administration of the IP.
Full blinding of trial personnel, Sponsor, and participants will be maintained until database lock at the conclusion of the trial.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults ≥18 years old.
- •Able to swallow capsules.
- •If of childbearing potential, agree to practice an effective means of birth control throughout the duration of the study.
- •Meet the DSM-5-TR criteria for a diagnosis of major depressive disorder and are currently experiencing a major depressive episode of at least a 60-day duration at the time of Screening.
- •Have at least moderate severity of depression symptoms at Screening and Trial Baseline.
排除标准
- •Participants who are pregnant, who intend to become pregnant during the trial, or who are currently nursing.
- •Have any of the following cardiovascular conditions: coronary artery disease, congenital long QT syndrome, cardiac hypertrophy, cardiac ischemia, congestive heart failure, clinically-relevant valvular heart disease, pulmonary hypertension, myocardial infarction, a clinically significant ECG abnormality, or tachycardia.
- •Have elevated blood pressure.
- •Have neurological conditions such as stroke, including transient ischemic attack, epilepsy, neurodegenerative disease (e.g., dementia, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, etc.), or brain tumor.
- •Have severe hepatic or renal impairment.
- •Have uncontrolled diabetes mellitus or unstable existing thyroid disorder.
- •Are hepatitis or HIV positive.
- •Have a positive urine drug test for illicit, non-prescribed, or prohibited substances.
- •Meet DSM-5-TR criteria for schizophrenia spectrum or other psychotic disorders, including major depressive disorder with psychotic features ,bipolar disorder (types 1 or 2), antisocial personality disorder, borderline personality disorder or moderate or severe alcohol or drug use disorder
- •Meet DSM-5-TR criteria for active post-traumatic stress disorder within 6 months prior to Screening.
- •Have a first-degree relative with schizophrenia spectrum or other psychotic disorders, or bipolar I disorder.
研究组 & 干预措施
Long-Term Follow-Up
After the initial 6-week Double-blind Period, all participants will proceed to a 1-year Follow-up Period. Participants will be followed via in-clinic visits and telephone visits during which clinic staff will assess changes in MDD symptom severity and safety measures including concomitant medications, adverse events (AEs), and suicidal ideation and behavior.
Participants will also engage in group psychosocial support sessions, including psychoeducation, throughout this period.
Participants may also be eligible to receive open-label re-administration(s) of Psilocybin 25 mg under the "Set and Setting" (SaS) Protocol if re-administration eligibility criteria are met.
干预措施: Psilocybin 25 mg (Drug)
Long-Term Follow-Up
After the initial 6-week Double-blind Period, all participants will proceed to a 1-year Follow-up Period. Participants will be followed via in-clinic visits and telephone visits during which clinic staff will assess changes in MDD symptom severity and safety measures including concomitant medications, adverse events (AEs), and suicidal ideation and behavior.
Participants will also engage in group psychosocial support sessions, including psychoeducation, throughout this period.
Participants may also be eligible to receive open-label re-administration(s) of Psilocybin 25 mg under the "Set and Setting" (SaS) Protocol if re-administration eligibility criteria are met.
干预措施: Psychosocial Support (Behavioral)
Psilocybin 5 mg
During the Double-blind Period, participants randomized to receive Psilocybin 5 mg will receive a single dose administered orally as a capsule and taken with water, along with the "Set and Setting" (SaS) Protocol.
The "Set and Setting" (SaS) Protocol includes preparatory meetings with two Facilitators prior to dosing, a 7-10 hour dosing session in a comfortable room under the supervision of the same two Facilitators, and 4 hours of post-dose integration sessions with Facilitators. During the dosing session, participants are encouraged to wear eyeshades and listen to a curated playlist on headphones.
干预措施: Psilocybin 5 mg (Drug)
Inactive Placebo
During the Double-blind Period, participants randomized to receive inactive placebo will receive a single dose of Microcrystalline Cellulose (MCC) 25 mg administered orally as a capsule and taken with water, along with the "Set and Setting" (SaS) Protocol.
The "Set and Setting" (SaS) Protocol includes preparatory meetings with two Facilitators prior to dosing, a 7-10 hour dosing session in a comfortable room under the supervision of the same two Facilitators, and 4 hours of post-dose integration sessions with Facilitators. During the dosing session, participants are encouraged to wear eyeshades and listen to a curated playlist on headphones.
干预措施: Inactive Placebo (Drug)
Psilocybin 25 mg
During the Double-blind Period, participants randomized to receive Psilocybin 25 mg will receive a single dose administered orally as a capsule and taken with water, along with the "Set and Setting" (SaS) Protocol.
The "Set and Setting" (SaS) Protocol includes preparatory meetings with two Facilitators prior to dosing, a 7-10 hour dosing session in a comfortable room under the supervision of the same two Facilitators, and 4 hours of post-dose integration sessions with Facilitators. During the dosing session, participants are encouraged to wear eyeshades and listen to a curated playlist on headphones.
干预措施: Psilocybin 25 mg (Drug)
结局指标
主要结局
Change in central rater Montgomery-Asberg Depression Rating Scale (MADRS) total score from Baseline to Trial Day 43
时间窗: From Trial Baseline to Trial Day 43
The MADRS is a clinician-rated scale designed to measure depression severity and to detect changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition. The total (composite) MADRS score is used as the endpoint.
次要结局
- Change in central rater Clinical Global Impression-Severity (CGI-S) total score from Baseline to Trial Day 43(From Trial Baseline to Trial Day 43)
- Change in on-site rater administered Sheehan Disability Scale (SDS) score from Baseline to post-dose Day 43(From Trial Baseline to Trial Day 43)