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Completed

NCT Number: NCT05712187

Phase 2b Study of ALTO-100 in MDD

The purpose of this study is to determine efficacy differences between ALTO-100 and placebo, used either as monotherapy or adjunctively to an antidepressant, related to patient characteristics.

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Key information

Conditions

Major Depressive Disorder Depressive Disorder Depressive Disorder, Major Mental Disorders Mood Disorders

Age range

18 year–64 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Site 174, Birmingham, Alabama, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Have a diagnosis of moderate to severe major depressive disorder (MDD)
  • At baseline, either not taking an antidepressant medication, or currently taking a single SSRI, SNRI, mirtazapine, or bupropion for at least 6 weeks with no dose modifications in the past 2 weeks
  • Willing to comply with all study assessments and procedures
  • Must not be pregnant or breastfeeding at time of enrollment or throughout study

Exclusion criteria

  • Evidence of unstable medical condition
  • Diagnosed bipolar disorder, psychotic disorder, or dementia
  • Current moderate or severe substance use disorder
  • Has a history of hypersensitivity or allergic reaction to ALTO-100 or any of its components/excipients
  • Concurrent or recent participation in another clinical trial for mental illness involving an investigational product or device

Treatment and study plan

ALTO-100

Drug

ALTO-100 tablet BID

Placebo

Drug

Placebo tablet BID

Primary outcomes

  1. To assess efficacy of ALTO-100 versus placebo on symptoms of MDD in a pre-defined subgroup of participants as measured by the change from Day 1 to Week 6 on the Montgomery-Åsberg Depression Rating Scale (MADRS) total score.

    Time frame: Change assessed from Day 1 to Week 6

    MADRS is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment. The MADRS evaluates the following 10 items: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.

Secondary outcomes

  1. To assess efficacy of ALTO-100 versus placebo for symptoms of MDD in a pre-defined subgroup of participants who are taking ALTO-100 as monotherapy for MDD as measured by the change from Day 1 to Week 6 on the MADRS total score.

    Time frame: Change assessed from Day 1 to Week 6

    MADRS is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment. The MADRS evaluates the following 10 items: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.

  2. To assess efficacy of ALTO-100 versus placebo on symptoms of MDD in all randomized participants as measured by the change from Day 1 to Week 6 on the Montgomery-Åsberg Depression Rating Scale (MADRS)

    Time frame: Assessed 4 times over a 6 week interval, from Day 1 to Week 6

    MADRS is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment. The MADRS evaluates the following 10 items: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.

  3. To assess efficacy of ALTO-100 versus placebo for MDD as measured by the change from Day 1 to Week 6 in Clinician Global Impression Scale-severity (CGI-S).

    Time frame: Assessed 4 times over a 6 week interval, from Day 1 to Week 6

    The CGI-S is a 7-point global assessment scale that measures the clinician's impression of the severity of illness exhibited by a participant, rating according to: 1=normal (not at all ill); 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; and 7=among the most extremely ill participants. Higher scores represent a more severe condition.

  4. To assess efficacy of ALTO-100 vs placebo for MDD as measured by the change from Day 1 to Week 6 in response (>50% improvement from baseline) and remission (total MADRS score of <10) rates based on the Montgomery-Åsberg Depression Rating Scale (MADRS)

    Time frame: Assessed 4 times over a 6- week interval, from Day 1 to Week 6

    MADRS is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment. The MADRS evaluates the following 10 items: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.

  5. To assess efficacy of ALTO-100 versus placebo for MDD as measured by the change from Day 1 to Week 6 in Patient Health Questionnaire, 9 item (PHQ-9).

    Time frame: Assessed 4 times over a 6- week interval, from Day 1 to Week 6

    The PHQ-9 is a 9-item, participant reported outcome measure to assess depressive symptoms. The scale scores each of the 9 symptom domains of the diagnostic and statistical manual of mental disorders-5th edition (DSM-5) major depressive disorder (MDD) criteria. Each item is rated on a 4- point scale (0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day). The participant's item responses are summed to provide a total score (range of 0 to 27), with higher scores indicating greater severity of depressive symptoms.

  6. To evaluate the safety of ALTO-100 during both the OL and DB periods of the study as measured by the assessment of the incidence, severity, and relatedness of Adverse Events.

    Time frame: Assessed from Day 1 to Week 13

    Incidence, severity, and relatedness of Adverse Events.

  7. To evaluate the safety of ALTO-100 during both the OL and DB periods of the study as measured by the assessment of Heart Rate.

    Time frame: Assessed from Day 1 to Week 13

    Assessment of Heart Rate.

  8. To evaluate the safety of ALTO-100 during both the OL and DB periods of the study as measured by the assessment of Blood Pressure.

    Time frame: Assessed from Day 1 to Week 13

    Assessment of Blood Pressure.

  9. To evaluate the safety of ALTO-100 during both the OL and DB periods of the study as measured by the assessment of Weight.

    Time frame: Assessed from Day 1 to Week 13

    Assessment of Weight.

  10. To evaluate the safety of ALTO-100 during both the OL and DB periods of the study as measured by the assessment of suicidality with the Concise Health Risk Tracking Self-Report,12 item scale (CHRT-SR12).

    Time frame: Assessed from Day 1 to Week 13

    The CHRT is a brief, self-report measure that systematically assesses both suicidal thinking and associated thoughts that may indicate the propensity for suicidal acts. The CHRT-SR12 is a 12 item scale. The patient assigns a score of 0-4 for each item of the scale, allowing for a total score of 0 to 48, with the higher score signifying more severe symptoms.

Sponsors and collaborators

Lead sponsor

Alto Neuroscience

Industry

Registry information

Official study title

A Randomized, Double-Blind, Placebo-Controlled Study of ALTO-100 With an Open-Label Extension in Adults With Major Depressive Disorder

Important dates

Study start
2023
Primary completion
2024
Study completion
2024
First posted
Feb 3, 2023
Registry last updated
Sep 8, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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