Psilocybin for Major Depressive Disorder (MDD) (uAspire)

Usona Institute

Status and phase: Enrolling; Phase 3

Conditions: Depressive Disorder, Major

Treatments: Drug: Psilocybin 25 mg; Drug: Psilocybin 5 mg; Drug: Inactive Placebo; Behavioral: Psychosocial Support

Study type: Interventional

Funder types: Other

Identifiers

NCT06308653

PSIL301

Details and patient eligibility

About

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.

Full description

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:

After the initial 6-week Double-blind Period and completion of the post-dosing Trial Day 43 assessments, all participants will proceed into a 1-year Follow-up Period.

During the 1-year Follow-up Period, participants will be followed regularly by clinic staff to assess MDD symptom severity, functional disability, and health-related quality of life; long-term safety data will also be collected. In addition to scheduled clinic visits, clinic staff will contact participants by telephone every two weeks to assess for changes in MDD symptom severity, concomitant medications, adverse events (AEs), and suicidal ideation and behavior.

Participants who meet the pre-defined MDD severity criteria and meet all re-administration eligibility criteria may be offered re-administration(s) of open-label Psilocybin 25 mg administered under a "Set and Setting" (SaS) Protocol. Psychosocial support, including psychoeducation, is also incorporated in the long-term Follow-up Period.

Enrollment: 240 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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240 participants in 4 patient groups, including a placebo group

Psilocybin 25 mg

Experimental group

Description:

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.

Treatment:

Drug: Psilocybin 25 mg

Psilocybin 5 mg

Active Comparator group

Description:

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.

Treatment:

Drug: Psilocybin 5 mg

Inactive Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Inactive Placebo

Long-Term Follow-Up

Other group

Description:

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.

Treatment:

Behavioral: Psychosocial Support

Drug: Psilocybin 25 mg