ALTO-300 in Depression

• ClinicalTrials.gov Identifier: NCT05118750
• Recruitment Status: Completed
• First Posted: November 12, 2021
• Last Update Posted: April 30, 2024
• Sponsor: Alto Neuroscience
• Information provided by (Responsible Party): Alto Neuroscience

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Major Depressive Disorder	Drug: ALTO-300 oral (PO) tablet	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 91 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label Study of ALTO-300 in Adults With Major Depressive Disorder
• Actual Study Start Date: December 13, 2021
• Actual Primary Completion Date: May 5, 2023
• Actual Study Completion Date: May 9, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: ALTO-300; ALTO-300 oral (PO) tablet; daily dosing 8 weeks	Drug: ALTO-300 oral (PO) tablet; One tablet daily

Outcome Measures

Primary Outcome Measures :

1. To understand the relationship between baseline biology and clinical outcome to ALTO-300 using the Montgomery-Åsberg Depression Rating Scale (MADRS) [ Time Frame: Measured 6 times over 8 weeks ]
   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.
2. To understand the relationship between baseline biology and clinical outcome to ALTO-300 using the Clinical Global Impression scale - Severity (CGI-S) [ Time Frame: Measured 6 times over 8 weeks ]
   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.
3. To evaluate the safety of ALTO-300 [ Time Frame: From the signing of the ICF until the follow-up visit (up to 12 weeks) ]
   Incidence, severity, and relatedness of TEAEs,SAEs, discontinuation due to TEAEs, and deaths
4. To evaluate the safety of ALTO-300 [ Time Frame: From the signing of the ICF until the end-of-treatment visit (up to 11 weeks) ]
   Assessment of vital signs and laboratory data, withparticular attention to liver function tests

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 74 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, California

Site 153

Culver City, California, United States, 90230

Site 103

Sacramento, California, United States, 95757

Site 158

Santee, California, United States, 92071

United States, Florida

Site 159

Clermont, Florida, United States, 34711

Site 161

Okeechobee, Florida, United States, 34972

United States, Indiana

Site 137

Noblesville, Indiana, United States, 46060

United States, Missouri

Site 166

Saint Charles, Missouri, United States, 63304

United States, New York

Site 132

New York, New York, United States, 10023

United States, Texas

Site 102

Dallas, Texas, United States, 75235

Site 165

DeSoto, Texas, United States, 75115

Site 147

Fort Worth, Texas, United States, 76104

Sponsors and Collaborators

Alto Neuroscience

More Information

• Responsible Party: Alto Neuroscience
• ClinicalTrials.gov Identifier: NCT05118750
• Other Study ID Numbers: ALTO-300-002
• First Posted: November 12, 2021
• Last Update Posted: April 30, 2024
• Last Verified: April 2024

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Depressive Disorder; Depression; Depressive Disorder, Major; Mood Disorders; Mental Disorders; Behavioral Symptoms