Phase 2b Study of ALTO-100 in MDD

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

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.

Study Overview

• Status: Recruiting
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Placebo; Drug: ALTO-100

• Study Type: Interventional
• Enrollment (Estimated): 266
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Alto Neuroscience; Phone Number: 650-200-0412; Email: clinical@altoneuroscience.com

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Recruiting
      • Site 174
    • Huntsville, Alabama, United States, 35801
      • Recruiting
      • Site 173
  • Arizona
    • Chandler, Arizona, United States, 85226
      • Recruiting
      • Site 136
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Recruiting
      • Site 139
  • California
    • Costa Mesa, California, United States, 92626
      • Recruiting
      • Site 141
    • Fresno, California, United States, 93703
      • Recruiting
      • Site 118
    • Imperial, California, United States, 92251
      • Recruiting
      • Site 181
    • Oceanside, California, United States, 92056
      • Recruiting
      • Site 182
    • Oceanside, California, United States, 92056
      • Recruiting
      • Site 188
    • Rancho Cucamonga, California, United States, 91730
      • Active, not recruiting
      • Site 179
    • Sacramento, California, United States, 95655
      • Recruiting
      • Site 116
  • Colorado
    • Centennial, Colorado, United States, 80112
      • Recruiting
      • Site 185
  • Florida
    • Brooksville, Florida, United States, 34613
      • Recruiting
      • Site 186
    • Jacksonville, Florida, United States, 32256
      • Recruiting
      • Site 204
    • Orlando, Florida, United States, 32801
      • Recruiting
      • Site 205
    • Tampa, Florida, United States, 33629
      • Recruiting
      • Site 212
    • Tampa, Florida, United States, 33629
      • Recruiting
      • Site 213
  • Indiana
    • Carmel, Indiana, United States, 46032
      • Recruiting
      • Site 137
  • Maryland
    • Baltimore, Maryland, United States, 21229
      • Recruiting
      • Site 151
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Recruiting
      • Site 171
    • Jackson, Mississippi, United States, 39216
      • Recruiting
      • Site 108
  • Nebraska
    • Lincoln, Nebraska, United States, 68562
      • Recruiting
      • Site 142
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • Recruiting
      • Site 144
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Recruiting
      • Site 178
  • New York
    • Brooklyn, New York, United States, 11229
      • Recruiting
      • Site 184
    • New York, New York, United States, 10022
      • Recruiting
      • Site 180
    • New York, New York, United States, 10128
      • Recruiting
      • Site 210
  • Ohio
    • Westlake, Ohio, United States, 44145
      • Recruiting
      • Site 175
  • South Carolina
    • North Charleston, South Carolina, United States, 29405
      • Recruiting
      • Site 157
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Recruiting
      • Site 183
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Recruiting
      • Site 147
    • Houston, Texas, United States, 77054
      • Recruiting
      • Site 120
    • Houston, Texas, United States, 77081
      • Recruiting
      • Site 172
  • Utah
    • Draper, Utah, United States, 84020
      • Recruiting
      • Site 121

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ALTO-100; Participants 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).	Drug: ALTO-100; ALTO-100 tablet BID
Placebo Comparator: Placebo DB; Participants will receive matching placebo tablet twice daily, from Day 1 to Day 42 in double blind (DB) treatment period.	Drug: Placebo; Placebo tablet BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	Change assessed from Day 1 to Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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.	Assessed 4 times over a 6 week interval, from Day 1 to Week 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.	Incidence, severity, and relatedness of Adverse Events.	Assessed from Day 1 to Week 13
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.	Assessment of Heart Rate.	Assessed from Day 1 to Week 13
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.	Assessment of Blood Pressure.	Assessed from Day 1 to Week 13
To evaluate the safety of ALTO-100 during both the OL and DB periods of the study as measured by the assessment of Weight.	Assessment of Weight.	Assessed from Day 1 to Week 13
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).	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.	Assessed from Day 1 to Week 13
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.	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.	Change assessed from Day 1 to Week 6
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)	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.	Assessed 4 times over a 6 week interval, from Day 1 to Week 6
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)	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.	Assessed 4 times over a 6- week interval, from Day 1 to Week 6
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).	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.	Assessed 4 times over a 6- week interval, from Day 1 to Week 6

Collaborators and Investigators

• Sponsor: Alto Neuroscience
• Investigators: Study Director: Adam Savitz, MD, PhD, Alto Neuroscience

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2023
• Primary Completion (Estimated): August 2, 2024
• Study Completion (Estimated): September 27, 2024

Study Registration Dates

• First Submitted: December 24, 2022
• First Submitted That Met QC Criteria: January 25, 2023
• First Posted (Actual): February 3, 2023

Study Record Updates

• Last Update Posted (Estimated): January 11, 2024
• Last Update Submitted That Met QC Criteria: January 10, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: ALTO-100-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No