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

Tracking Information

• First Submitted Date: October 18, 2021
• First Posted Date: November 12, 2021
• Last Update Posted Date: April 30, 2024
• Actual Study Start Date: December 13, 2021
• Actual Primary Completion Date: May 5, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 19, 2023)

• 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.
• 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.
• 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
• 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

Original Primary Outcome Measures (submitted: November 2, 2021)

• To understand the relationship between baseline biology and clinical outcome with 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.
• To understand the relationship between baseline biology and clinical outcome with 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.
• Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability of ALTO-300 [ Time Frame: From the signing of the ICF until the follow-up visit (up to 12 weeks) ]
  An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
• Number of Participants With Clinically Significant Vital Signs Abnormalities as a Measure of Safety and Tolerability of ALTO-300 [ Time Frame: From the signing of the ICF until the end-of-treatment visit (up to 11 weeks) ]
  Vital signs measured include blood pressure, heart rate, respiratory rate, temperature, and weight.
• Number of Participants With Clinically Significant Laboratory Abnormalities as a Measure of Safety and Tolerability of ALTO-300 [ Time Frame: From the signing of the ICF until the end-of-treatment visit (up to 11 weeks) ]
  Blood samples for serum chemistry and hematology will be collected for clinical laboratory testing.

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: ALTO-300 in Depression
• Official Title: An Open-label Study of ALTO-300 in Adults With Major Depressive Disorder
• Brief Summary: The purpose of this study is to collect biologically-based data for defining predictors and correlates of the effects of ALTO-300.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Major Depressive Disorder

Intervention

Drug: ALTO-300 oral (PO) tablet

One tablet daily

Study Arms

Experimental: ALTO-300

ALTO-300 oral (PO) tablet; daily dosing 8 weeks

Intervention: Drug: ALTO-300 oral (PO) tablet

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 19, 2023): 91
• Original Estimated Enrollment (submitted: November 2, 2021): 200
• Actual Study Completion Date: May 9, 2023
• Actual Primary Completion Date: May 5, 2023 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 74 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05118750
• Other Study ID Numbers: ALTO-300-002
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Alto Neuroscience
• Original Responsible Party: Same as current
• Current Study Sponsor: Alto Neuroscience
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Alto Neuroscience
• Verification Date: April 2024