ALTO-300 in Depression

Major Depressive Disorder Clinical Trial

Official title:

An Open-label Study of ALTO-300 in Adults With Major Depressive Disorder

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05118750
• Other study ID #: ALTO-300-002
• Status: Completed
• Phase: Phase 2
• Start date: December 13, 2021
• Est. completion date: May 9, 2023

Study information

• Verified date: April 2024
• Source: Alto Neuroscience
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to collect biologically-based data for defining predictors and correlates of the effects of ALTO-300.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 91
• Est. completion date: May 9, 2023
• Est. primary completion date: May 5, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 74 Years

Eligibility

Inclusion Criteria:

• have a diagnosis of MDD based on the Structured Clinical Interview for DSM-5 (SCID) for depression

• have moderate to severe depression on DSM-5 depression criteria items, as assessed by a score of =10 on the Patient Health Questionnaire-9 (PHQ-9) at each of Visits 1, 2, and 3

• at baseline (Visit 2) are taking a stable dose of a single SSRI, serotonin-norepinephrine reuptake inhibitor (SNRI), or bupropion and have been on that medication for =6 weeks at an adequate dosage defined by the Antidepressant Treatment Response Questionnaire (ATRQ), and with no modification to dosage for =2 weeks.

• have either: had a continuous period of euthymia of at least 2 months in the past 26 months, regardless of the number of failed antidepressants OR not had a period of euthymia of at least 2 months in the past 26 months but within the past 24 months have not failed >3 antidepressants at an adequate dosage and duration as defined by the ATRQ

• are currently on their last failed currently prescribed permitted baseline antidepressant medication

• have a response to their currently prescribed antidepressant noted as depression that has improved =49% as defined by the ATRQ.

• agree to, and are eligible for all biomarker assessments (EEG, neurocognitive testing, activity and sleep monitoring, genetic testing). To participate in the activity and sleep monitoring biomarkers, all participants will be required to have a smart phone or an internet enabled tablet. A participant who otherwise qualifies may refuse the salivary genetic sample and be included in the study.

• fluent in English

• willing to comply with all study procedures (with the notes above), able to complete all assessments independently, and available for the duration of the study.

Exclusion Criteria:

Any of the following medical conditions:

• hepatic impairment (i.e., cirrhosis or active/chronic liver disease)

• baseline serum transaminase levels that exceed 2x upper limit of normal(ULN)

• severe impediment to vision, hearing, comprehension, and/or hand movement that interferes with study tasks.

• any contraindications to EEG (i.e., requiring high concentration oxygen)

• active suicidal ideation as assessed by the investigator.

• moderate to severe Alcohol Use Disorder (AUD)

Concurrent use of any of the following at baseline (Visit 2):

• tricyclic antidepressants (TCAs), mirtazapine, or monoamine oxidase inhibitors (MAOIs)

• melatonin, ramelteon, or other melatonin agonist

• a potent CYP1A2 inhibitor (e.g., fluvoxamine and ciprofloxacin)

• antipsychotics or mood stabilizers

• hypnotics, anxiolytics, stimulants, or opiate pain medications greater than three days per week and unable to reduce use to 3 or fewer days per week on an as needed basis

Have received electroconvulsive therapy (ECT), deep brain stimulation (DBS),vagus nerve stimulation (VNS), >2 treatments with ketamine, or esketamine in thecurrent depressive episode.

Diagnosis of bipolar disorder or a psychotic disorder based on the SCID forDSM-5

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Drug:
• ALTO-300 oral (PO) tablet
One tablet daily

Locations

Country	Name	City	State
United States	Site 159	Clermont	Florida
United States	Site 153	Culver City	California
United States	Site 102	Dallas	Texas
United States	Site 165	DeSoto	Texas
United States	Site 147	Fort Worth	Texas
United States	Site 132	New York	New York
United States	Site 137	Noblesville	Indiana
United States	Site 161	Okeechobee	Florida
United States	Site 103	Sacramento	California
United States	Site 166	Saint Charles	Missouri
United States	Site 158	Santee	California

Sponsors (1)

Lead Sponsor	Collaborator
Alto Neuroscience

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To understand the relationship between baseline biology and clinical outcome to ALTO-300 using the Montgomery-Åsberg Depression Rating Scale (MADRS)	The Montgomery-Åsberg Depression Rating Scale (MADRS) measures the severity of depression where smaller scores indicate less depression and higher scores suggest more severe depression. Possible scores for this 10 item version range from 0 to 60. The change from baseline to the end of the study is the primary outcome.	Measured 6 times over 8 weeks
Primary	To understand the relationship between baseline biology and clinical outcome to ALTO-300 using the Clinical Global Impression scale - Severity (CGI-S)	The Clinical Global Impression scale - Severity (CGI-S) measures the severity of psychopathology in general where smaller scores indicate less illness and higher scores suggest more severe illness. Possible scores for this scale range from 1 to 7. The change from baseline to the end of the study is the primary outcome.	Measured 6 times over 8 weeks
Primary	To evaluate the safety of ALTO-300	Incidence, severity, and relatedness of TEAEs,SAEs, discontinuation due to TEAEs, and deaths	From the signing of the ICF until the follow-up visit (up to 12 weeks)
Primary	To evaluate the safety of ALTO-300	Assessment of vital signs and laboratory data, withparticular attention to liver function tests	From the signing of the ICF until the end-of-treatment visit (up to 11 weeks)