Apimostinel + Automated Neurocognitive Training for Depression

NCT06400121 | Recruiting Phase 2 FDA Drug

• 1 other identifier: STUDY24010064
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

Apimostinel shows initial promise as a novel rapid-acting antidepressant medication with minimal side effects or safety concerns. Cognitive Training (CT) is a digital intervention that has shown promise in extending the durability of another similar drug (ketamine). This randomized controlled trial will test the efficacy and safety of apimostinel (vs. placebo) for the acute treatment of depression, and will test the potential of CT to enhance and/or extend the durability of apimostinel's antidepressant effect.

Conditions

Depression

Outcome Measures

Primary Outcomes (2)

• Montgomery-Asberg Depression Rating Scale (MADRS)

  interviewer-rated depression severity, comparing both apimostinel arms (collapsing active and sham CT arms) to placebo+CT arm; range 0-60; high score=worse outcome

  Trajectories from baseline/screening through 5 days post infusion

• Montgomery-Asberg Depression Rating Scale (MADRS)

  interviewer-rated depression severity, comparing apimostinel+CT to placebo+CT arm; range 0-60; high score=worse outcome

  Trajectories from baseline/screening through 45 days post infusion

Secondary Outcomes (3)

• Quick Inventory of Depressive Symptoms

  Trajectories from baseline/screening through 45 days post infusion

• Quick Inventory of Depressive Symptoms

  Trajectories from baseline/screening through 6 months post infusion

• Montgomery-Asberg Depression Rating Scale (MADRS)

  Trajectories from baseline/screening through 6 months post infusion

Other Outcomes (13)

• Clinician-Administered Dissociative States Scale (CADSS)

  Trajectories from baseline through 120 min post infusion

• Brief Psychiatric Rating Scale--4 item psychosis subscale (BPRS+)

  Trajectories from baseline through 120 min post infusion

• Time to onset of effect on MADRS

  Assessed at each study visit from Day 1 to Month 6

Study Arms (3)

Apimostinel + Cognitive Training

EXPERIMENTAL

Drug: Apimostinel Infusion, Intravenous; Behavioral: Cognitive Training

Apimostinel + Sham Training

SHAM COMPARATOR

Drug: Apimostinel Infusion, Intravenous; Behavioral: Sham Training

Placebo + Cognitive Training

PLACEBO COMPARATOR

Behavioral: Cognitive Training; Drug: Isotonic Solution, Intravenous

Interventions

Apimostinel Infusion, Intravenous DRUG

Single injection of Apimostinel (10mg)

Apimostinel + Cognitive Training; Apimostinel + Sham Training

Cognitive Training BEHAVIORAL

8 sessions of digital active training

Apimostinel + Cognitive Training; Placebo + Cognitive Training

Sham Training BEHAVIORAL

8 sessions of digital sham training

Apimostinel + Sham Training

Isotonic Solution, Intravenous DRUG

Single injection of placebo

Placebo + Cognitive Training

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Participants of any gender are eligible
• Aged 18 to 60 years
• Meets Diagnostic and Statistical Manual, Fifth Edition (DSM-V) criteria for major depressive disorder (MDD)
• MADRS score ≥ 20 at screening
• Score \>1SD above the normative mean on the Cognitive Triad Inventory (CTI) "self" subscale \*OR\* \<1SD below the normative mean on the Rosenberg self-esteem scale
• Participants of childbearing potential with a negative serum pregnancy test prior to entry into the study and who are practicing an adequate method of birth control (eg oral or parenteral contraceptives, intrauterine device, barrier, abstinence) and who do not plan to become pregnant during the course of the study. Participants may be included without a negative serum pregnancy test if they are surgically sterile or at least 2 years post- menopausal. Participants who could impregnate a sexual partner should use an acceptable method of birth control during the study, from the day of dosing to 28 days following dose.
• Participants who could impregnate a partner and their sexual partner of childbearing potential should use an acceptable method of birth control during the study, from day of dosing to 28 days following dose.
• Clinical laboratory values \< 1.5 times the upper limit of normal (ULN) or deemed not clinically significant per the investigator
• Ability to understand the requirements of the study, provide written informed consent, abide by the study restrictions, and agree to return for the required assessments
• Based on the investigator's clinical judgment, participants with eating disorders, obsessive compulsive disorder (OCD), panic disorder, post-traumatic stress disorder (PTSD), and generalized anxiety disorders secondary to major depressive episodes are permitted.

You may not qualify if:

• Presence of lifetime bipolar, psychotic, or autism spectrum; or current problematic, moderate-to-severe substance use disorder
• Use of a Monoamine Oxidase Inhibitor (MAOI) within 28 days of infusion date
• Huntington's, Parkinson's, Alzheimer's, Multiple Sclerosis, or a history of strokes or with one or more seizures without a clear and resolved etiology
• Currently hospitalized or residing in an in-patient facility during the study participation
• Changes made to treatment regimen within 28 days of drug infusion (Day 0)
• Reading level \<6th grade as per patient self-report
• Serious, unstable medical illnesses including respiratory \[obstructive sleep apnea, or history of difficulty with airway management during previous anesthetics\], cardiovascular \[including ischemic heart disease and uncontrolled hypertension\], and neurologic \[including history of severe head injury diagnoses.
• Clinically significant abnormal findings of laboratory parameters \[including urine toxicology screen for drugs of abuse\], physical examination, or ECG.
• Uncontrolled or poorly controlled hypertension, as determined by the study physician's review of vitals collected during screening and any other relevant medical history/records.
• Patient has clinically significant renal dysfunction as assessed by the estimated glomerular filtration rate \<70 mL/min using the Chronic Kidney Disease Epidemiology Collaboration -creatinine methodology.
• Patient has liver enzyme test results \>2 times the upper limit of normal.
• Patient has resting heart rate (supine) \<60 or \>100 bpm at the Screening Visit or Pre-Dose Baseline, in the absence of an etiology that, in the judgment of the investigator, is related to exceptionally good cardiovascular fitness.
• Patient has PR interval \>250 msec at the Screening Visit or Pre-Dose Baseline
• Patients starting hormonal treatment (e.g., estrogen) in the 3 months prior to Screening.
• Patients taking medications with known activity at the NMDA or AMPA glutamate receptor \[e.g., riluzole, amantadine, memantine, topiramate, dextromethorphan (including AuvelityTM), D-cycloserine, ketamine or esketamine\], or the mu-opioid receptor.

Sponsors & Collaborators

• Rebecca Price: lead
• Syndeio Biosciences, Inc: collaborator

Study Sites (1)

Western Psychiatric Institute and Clinic

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

MeSH Terms

Conditions

Depression

Interventions

Cognitive Training; Isotonic Solutions

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Neurological Rehabilitation; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Health Services; Health Care Facilities Workforce and Services; Solutions; Pharmaceutical Preparations

Study Officials

• Rebecca B Price, PhD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rebecca B Price, PhD

CONTACT

4123832150; canlab@pitt.edu

Crystal Spotts, M.Ed.

CONTACT

412-246-5764; spottscr@upmc.edu

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: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Psychiatry and Psychology

Study Record Dates

• First Submitted: May 1, 2024
• First Posted: May 6, 2024
• Study Start: October 28, 2024
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: September 24, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)