A study of a deuterated psilocin analog (CYB003) in humans with major depressive disorder (APPROACH)

General information:

Protocol Title: A Phase III, Placebo-Controlled, Randomized, Double-Blind Trial of Oral Doses of CYB003 to Assess Combined Safety and Efficacy in Humans with Major Depressive Disorder (APPROACH)

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Study summary:

The APPROACH trial is exploring an investigational psychedelic medication, combined with psychological support, to learn how effective it might be at reducing symptoms of Major Depressive Disorder (MDD).

Phase of study

Phase III

Eligibility

Age

18-85

Gender

All

Condition

MDD (Major Depressive Disorder)

Inclusion criteria

• You are 18 to 85 years old
• You have been diagnosed with Major Depressive Disorder (MDD) by a healthcare professional. Your first episode of depression occurred before age 60
• Your depression is currently moderate to severe. You have been taking one antidepressant medication at a stable dose for at least 4 weeks. Your antidepressant has not reduced your symptoms by 50% or more
• You are willing to avoid nicotine (smoking, vaping, or nicotine products) during the study dosing visit (up to 8 hours)
• Participants who could become pregnant must use reliable birth control during the study and have negative pregnancy tests. Participants who could cause a pregnancy must use condoms with spermicide. These precautions continue during the study and for 12 weeks after the last dose
• Postmenopausal or permanently sterile participants do not need birth control
• You are willing to review and sign an informed consent form, which explains the study in detail, including possible risks and benefits

Exclusion criteria

• You have ever been diagnosed with schizophrenia, bipolar disorder type I, or another psychotic disorder. You are currently at high risk for suicide
• You have severe or treatment-resistant depression (two or more antidepressants did not help)
• You received ECT, TMS, ketamine, or esketamine within the past 6 months. You have recently used psychedelic drugs or have had a substance use disorder in the past year
• You have uncontrolled high blood pressure or significant heart rhythm problems. Individuals with well-controlled blood pressure on stable medication may still be eligible.
• You have a history of seizures, serious brain conditions, or Brain tumors.
• Moderate to severe liver abnormalities. In some cases, repeat testing may be allowed if results are borderline and not medically concerning.:
• Individuals with substance use disorder in the past year (excluding caffeine or nicotine) are not eligible
• Alcohol must be avoided 48 hours before screening and before study visits. Positive drug or alcohol tests at screening or dosing visits may result in exclusion
• Marijuana use may be allowed only if stopped during the study, and drug tests remain negative
• Used MAO inhibitors within the past 14 days. Pregnant or breastfeeding individuals cannot participate
• Participants must not be planning a pregnancy during the study. Egg or sperm donation is not allowed during the study and for 12 weeks after the final dose
• Employees or close family members of the study sponsor or research staff are not eligible

Study description

The APPROACH trial is exploring an investigational psychedelic medication, combined with psychological support, to learn how effective it might be at reducing symptoms of major depressive disorder (MDD).

In recent years there has been growing interest in the potential role psychedelic medications could play in the treatment of mental health conditions.

The investigational study medicine, called CYB003, is similar to psilocin (the active ingredient in Psilocybe mushrooms). Psychedelic medications, at certain doses, may cause an altered state of consciousness, unique thoughts, and changes in your senses, such as hearing, seeing, tasting, and/or smelling things that are not real. Psychological support and CYB003 given together may help people reach deeper into their thoughts, promote healing, and may be effective in treating MDD.

A licensed therapist with specialized training in EMBARK, a psychological support model for MDD, will work with participants during several psychological support sessions before and after the dosing sessions. They, along with a second session monitor, will also attend the dosing sessions for both psychological support and safety purposes.

Treatment or intervention being studied

You will be assigned randomly (like flipping a coin) to receive either CYB003 or a placebo combined with psychological support. A placebo is an inactive treatment which looks the same as the investigational study medicine but does not contain any active ingredient. Neither you nor the trial doctors will know which treatment you are taking, this is known as a ‘double-blinded’ trial.

CYB003 is given as a capsule to be swallowed whole. Participants will take the investigational study medicine at dosing sessions during clinic visits. They will have two dosing sessions in total, about three weeks apart.

During the dosing sessions, you may experience changes in how you hear and see things, feel, and think for several hours. Both of your session monitors will stay with you to provide support and take any necessary safety measures. You will be accompanied home by a trusted adult (friend or family member).

Participation summary and requirements

Participation is expected to last about four and a half months.

Participants will have a total of:

• 8 clinic visits
• 8 remote visits (by video call)

Most of the visits in this trial will last at least two hours. The two visits at which you have dosing sessions are expected to last at least 8 hours.

During the clinical trial, a team of doctors, researchers and healthcare professionals will take care of you and check on your progress. What happens at each clinic visit will vary, but activities may include: health review, physical examination, mental health review, vital signs, questionnaires, and blood and urine tests.

Participants will also have the option to join a long-term extension to the trial if they meet the requirements, where all participants can receive CYB003 with psychological support once they meet the requirements for dosing – there is no placebo group in this extension trial. The extension will last about 43 weeks.

Possible risks and side effects

CYB003 is an investigational drug, so unknown risks may exist. In prior trials, doses up to 16 mg were well tolerated, with mild to moderate side effects such as nausea, vomiting, increased blood pressure and heart rate, headache, dizziness, and anxiety. Effectiveness is not guaranteed, and symptoms may worsen. Placebo participants may see no improvement. Risks include allergic reactions (rarely severe), blood draw complications, ECG skin irritation, emotional discomfort from questionnaires, and potential privacy breaches during remote sessions. Pregnancy-related risks are unknown; strict contraception requirements apply for all participants.

Site location

This study is taking place at numerous sites across the country, including in Arizona, California, Colorado, Florida, Georgia, Illinois, Louisiana, Maryland, Massachusetts, Nevada, New Jersey, New York, North Carolina, Ohio, Tennessee, Texas, and Utah.

To learn more, please complete the pre-screening process.

Study contact name

To learn more, please complete the pre-screening process.

If your answers suggest that this clinical trial may be right for you, your contact information will be sent to the trial team at the trial site you select. The trial team will contact you to discuss the trial further and give you more information as well as answer any questions you may have.

Please note that Mental Health America has received financial support from clinical trial and study sponsors to share information about the clinical trials posted on this page. Mental Health America has not evaluated any clinical trials or studies. The information provided in these postings is for general information purposes only and does not represent an endorsement or recommendation from Mental Health America.