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Phase 2b Study of ALTO-100 in MDD

Phase 2
Active, not recruiting
Conditions
Major Depressive Disorder
Interventions
Drug: Placebo
Registration Number
NCT05712187
Lead Sponsor
Alto Neuroscience
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
301
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ALTO-100ALTO-100Participants will receive ALTO-100 tablet twice daily, from Day 1 to Day 42 in double blind (DB) treatment period. Eligible participants who will enter the open label (OL) treatment period will receive ALTO-100 tablet twice daily from OL baseline until the end of OL period/early termination visit (Up to 7 weeks).
Placebo DBPlaceboParticipants will receive matching placebo tablet twice daily, from Day 1 to Day 42 in double blind (DB) treatment period.
Primary Outcome Measures
NameTimeMethod
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.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 Outcome Measures
NameTimeMethod
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).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.

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.Assessed from Day 1 to Week 13

Assessment of Blood Pressure.

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.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.

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.Assessed from Day 1 to Week 13

Incidence, severity, and relatedness of Adverse Events.

To evaluate the safety of ALTO-100 during both the OL and DB periods of the study as measured by the assessment of Weight.Assessed from Day 1 to Week 13

Assessment of Weight.

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)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.

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.Assessed from Day 1 to Week 13

Assessment of Heart Rate.

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)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.

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).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.

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).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.

Trial Locations

Locations (34)

Site 173

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Huntsville, Alabama, United States

Site 118

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Fresno, California, United States

Site 179

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Rancho Cucamonga, California, United States

Site 108

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Jackson, Mississippi, United States

Site 141

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Costa Mesa, California, United States

Site 181

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Imperial, California, United States

Site 137

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Carmel, Indiana, United States

Site 120

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Houston, Texas, United States

Site 172

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Houston, Texas, United States

Site 180

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New York, New York, United States

Site 175

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Westlake, Ohio, United States

Site 210

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New York, New York, United States

Site 184

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Brooklyn, New York, United States

Site 157

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North Charleston, South Carolina, United States

Site 144

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Las Vegas, Nevada, United States

Site 174

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Birmingham, Alabama, United States

Site 212

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Tampa, Florida, United States

Site 213

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Tampa, Florida, United States

Site 136

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Chandler, Arizona, United States

Site 139

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Little Rock, Arkansas, United States

Site 182

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Oceanside, California, United States

Site 188

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Oceanside, California, United States

Site 185

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Centennial, Colorado, United States

Site 186

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Brooksville, Florida, United States

Site 204

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Jacksonville, Florida, United States

Site 151

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Baltimore, Maryland, United States

Site 171

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Jackson, Mississippi, United States

Site 142

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Lincoln, Nebraska, United States

Site 178

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Albuquerque, New Mexico, United States

Site 183

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Memphis, Tennessee, United States

Site 147

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Fort Worth, Texas, United States

Site 121

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Draper, Utah, United States

Site 116

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Sacramento, California, United States

Site 205

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Orlando, Florida, United States

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