Phase 2b Study of ALTO-100 in MDD

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ClinicalTrials.gov Identifier: NCT05712187

Recruitment Status : Recruiting

First Posted : February 3, 2023

Last Update Posted : January 11, 2024

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Sponsor:

Information provided by (Responsible Party):

Alto Neuroscience

Tracking Information

First Submitted Date ^ICMJE

December 24, 2022

First Posted Date ^ICMJE

February 3, 2023

Last Update Posted Date

January 11, 2024

Actual Study Start Date ^ICMJE

January 10, 2023

Estimated Primary Completion Date

August 2, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

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.

Original Primary Outcome Measures ^ICMJE

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 in the Montgomery-Åsberg Depression Rating Scale (MADRS). [ Time Frame: Change assessed from Day 1 to Week 6 ]

Change History

Current Secondary Outcome Measures ^ICMJE

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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

Original Secondary Outcome Measures ^ICMJE

To assess efficacy of ALTO-100 versus placebo on symptoms of MDD in all randomized participants. [ Time Frame: Change assessed from Day 1 to Week 6 ]
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.
To assess efficacy of ALTO-100 versus placebo for MDD. [ Time Frame: Assessed 4 times over a 6 week interval, from Day 1 to Week 6 ]
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.
To assess efficacy of ALTO-100 versus placebo for MDD. [ Time Frame: Assessed 4 times over a 6 week interval, from Day 1 to Week 6 ]
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.
To assess efficacy of ALTO-100 versus placebo for MDD. [ Time Frame: Assessed 4 times over a 6 week interval, from Day 1 to Week 6 ]
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.
To evaluate the safety of ALTO-100 during both the OL and DB periods of the study. [ Time Frame: 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. [ Time Frame: Assessed from Day 1 to Week 13 ]
Assessment of Heart Rate.
To evaluate the safety of ALTO-100 during both the OL and DB periods of the study. [ Time Frame: Assessed from Day 1 to Week 13 ]
Assessment of Blood Pressure.
To evaluate the safety of ALTO-100 during both the OL and DB periods of the study. [ Time Frame: Assessed from Day 1 to Week 13 ]
Assessment of Weight.
To evaluate the safety of ALTO-100 during both the OL and DB periods of the study. [ Time Frame: Assessed from Day 1 to Week 13 ]
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.

Current Other Pre-specified Outcome Measures

Not Provided

Original Other Pre-specified Outcome Measures

Not Provided

Descriptive Information

Brief Title ^ICMJE

Phase 2b Study of ALTO-100 in MDD

Official Title ^ICMJE

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

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 Provided

Study Type ^ICMJE

Interventional

Study Phase ^ICMJE

Phase 2

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Condition ^ICMJE

Major Depressive Disorder

Intervention ^ICMJE

Drug: ALTO-100
ALTO-100 tablet BID
Drug: Placebo
Placebo tablet BID

Study Arms ^ICMJE

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).

Intervention: Drug: ALTO-100
Placebo Comparator: Placebo DB
Participants will receive matching placebo tablet twice daily, from Day 1 to Day 42 in double blind (DB) treatment period.

Intervention: Drug: Placebo

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Recruiting

Estimated Enrollment ^ICMJE

266

Original Estimated Enrollment ^ICMJE

200

Estimated Study Completion Date ^ICMJE

September 27, 2024

Estimated Primary Completion Date

August 2, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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

Sex/Gender ^ICMJE

Sexes Eligible for Study:

All

Ages ^ICMJE

18 Years to 64 Years (Adult)

Accepts Healthy Volunteers ^ICMJE

Contacts ^ICMJE

Contact: Alto Neuroscience

650-200-0412

clinical@altoneuroscience.com

Listed Location Countries ^ICMJE

United States

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT05712187

Other Study ID Numbers ^ICMJE

ALTO-100-201

Has Data Monitoring Committee

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 ^ICMJE

Plan to Share IPD:

Current Responsible Party

Alto Neuroscience

Original Responsible Party

Same as current

Current Study Sponsor ^ICMJE

Alto Neuroscience

Original Study Sponsor ^ICMJE

Same as current

Collaborators ^ICMJE

Not Provided

Investigators ^ICMJE

Study Director:

Adam Savitz, MD, PhD

Alto Neuroscience

PRS Account

Alto Neuroscience

Verification Date

January 2024

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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