Study of ABX-002 for the Adjunctive Treatment of Depressive Episodes Associated With Bipolar Disorder in Adults

A Phase 2 Open-label Study of the Effect of Adjunctively Administered ABX-002 in Adults With Bipolar Disorder Experiencing an Episode of Depression

The goal of this clinical trial is to learn if ABX-002 added to participants' existing treatment(s) can improve clinical symptoms of depression and to learn about potential effects on brain chemistry that may correlate with antidepressive effects.

This is a single treatment arm, open-label, Phase 2 study of ABX-002 in up to30 adults with bipolar depression. A subset of these participants will undergo brain imaging. Five healthy volunteer participants will also be enrolled and receive no drug treatment, undergoing 2 imaging sessions to confirm instrument and test - retest method reliability control.

For bipolar disorder participants who are experiencing an episode of depression, the study will include 4 study periods:

1. Screening Period of up to 5 weeks
2. 6-week Treatment Period
3. 2-week post dose Safety Follow-up Period.
4. 6-month postdose targeted safety follow-up period

For healthy volunteers, the study will include 2 study periods:

1. Screening Period of up to 3 weeks
2. Imaging Period of up to 3 weeks.

Inclusion Criteria (For Bipolar Disorder Depression Patients):

• Current diagnosis of bipolar disorder for at least 2 years
• DSM-5-TR criteria for bipolar disorder based on Structured Clinical Interview for the DSM-5 - Clinical Trials Version (SCID-5-CT) at Screening
• Has a current depressive episode with or without mixed features, but not psychotic features, with duration ≥ 6 weeks and ≤ 24 months
• 17-item Hamilton Rating Scale for Depression total score ≥ 22 at Screening and Baseline
• Young Mania Rating Scale total score ≤ 12 at Screening and Baseline
• For participants who will undergo brain imaging: Able to undergo imaging sessions using Magnetic Resonance Spectroscopy/Imaging with no history of aborted scanning due to anxiety, claustrophobia, or unable to scan due to an incompatible implant/device
• Taking at least one mood stabilizer (e.g., lithium, valproate, lamotrigine) and/or second-generation antipsychotic (SGA, atypical antipsychotic). All medications intended to treat the current episode of depression should be at an adequate and stable dose for ≥ 6 weeks prior to screening.

Exclusion Criteria (For Bipolar Disorder Depression Patients):

• History of > 4 manic, hypomanic, or depressive episodes within a one-year period (rapid cycler; DSM-5-TR) in the last 2 years
• History of schizophrenia or schizoaffective disorder (DSM-5-TR) or a psychotic disorder unrelated to bipolar disorder
• Concurrent or history of active symptoms within the past 2 years of obsessive-compulsive disorder, or posttraumatic stress disorder, according to DSM-5-TR criteria
• Diagnosis of a personality disorder (DSM-5-TR)
• Evident risk of suicide at Screening or Baseline
• Inadequate response to more than 2 second-generation antipsychotic treatments (including their current treatment) in their current episode of depression in bipolar disorder despite an adequate dose and duration (> 6 weeks at approved or standard of care doses)
• Received any course of deep brain stimulation in participant's lifetime or plans to receive deep brain stimulation during the study
• Treatment with electroconvulsive therapy (for psychiatric/therapeutic purposes) or repetitive transcranial magnetic stimulation, or treatment with ketamine or esketamine for the current episode and received any of those treatments within 12 months prior to Screening
• Started new psychotherapy or had a change in the intensity of psychotherapy within 6 weeks before Screening
• Prior use of psychedelics for the treatment of depression
• Refusal to abstain from consumption of excessive amounts of alcohol during the study
• History of uncontrolled, clinically significant neurological (including prior cerebrovascular accident [stroke] or chronic seizures), cardiovascular, gastrointestinal, respiratory, renal, hepatic, immunological, hematological, endocrine (including uncontrolled diabetes), or other medical disorder, including cancer
• Current use of high dose (> 4 mg/day lorazepam equivalents) benzodiazepine anxiolytic and/or hypnotic medication
• Cannabinoids (marijuana, cannabis, tetrahydrocannabinol [THC], cannabidiol [CBD]) in any form or use frequency.
• History or presence of cataract on ophthalmic examination (including slit-lamp), glaucoma, inflammatory eye disease prior ophthalmic surgical procedures or laser surgery in either eye.

Inclusion Criteria (For Healthy Volunteers):

• In good health, based on medical history, physical examination (including neurological examination), vital sign measurements, and laboratory safety tests obtained at the Screening Visit
• Able to undergo imaging sessions using Magnetic Resonance Spectroscopy/Imaging, with no history of aborted scanning due to anxiety, claustrophobia, or an incompatible implant/device

Exclusion Criteria (Healthy Volunteers):

• Mentally or legally incapacitated, has significant emotional problems at the time of the Screening Visit, or is expected to have potential for mental incapacitation during the conduct of the study
• History of any illness (including psychiatric illness)
• Participation in an investigational drug or device study where last dosing of previous drug is within 30 days
• Prior use of psychedelics within the past year
• Refusal to abstain from consumption of excessive amounts of alcohol during the study
• Cannabinoids (marijuana, cannabis, tetrahydrocannabinol [THC], cannabidiol [CBD]) in any form or use frequency are not allowed.