Phase 2b Study of ALTO-100 in MDD

• ClinicalTrials.gov Identifier: NCT05712187
• Recruitment Status: Recruiting
• First Posted: February 3, 2023
• Last Update Posted: March 22, 2023
• Sponsor: Alto Neuroscience
• Information provided by (Responsible Party): Alto Neuroscience

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Major Depressive Disorder	Drug: ALTO-100; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled Study of ALTO-100 With an Open-Label Extension in Adults With Major Depressive Disorder
• Actual Study Start Date: January 10, 2023
• Estimated Primary Completion Date: January 16, 2024
• Estimated Study Completion Date: March 6, 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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 in the Montgomery-Åsberg Depression Rating Scale (MADRS). [ 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 Outcome Measures :

1. 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: 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 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Alto Neuroscience; 650-397-5693; clinical@altoneuroscience.com

Locations

United States, Arizona

Site 136; Recruiting

Chandler, Arizona, United States, 85226

United States, Arkansas

Site 139; Recruiting

Little Rock, Arkansas, United States, 72211

United States, California

Site 141; Recruiting

Costa Mesa, California, United States, 92626

Site 118; Recruiting

Fresno, California, United States, 93703

Site 179; Recruiting

Rancho Cucamonga, California, United States, 91730

Site 116; Recruiting

Sacramento, California, United States, 95655

United States, Indiana

Site 137; Not yet recruiting

Carmel, Indiana, United States, 46032

United States, Maryland

Site 151; Recruiting

Baltimore, Maryland, United States, 21229

United States, Mississippi

Site 171; Recruiting

Jackson, Mississippi, United States, 39216

United States, Nebraska

Site 142; Recruiting

Lincoln, Nebraska, United States, 68562

United States, Nevada

Site 144; Recruiting

Las Vegas, Nevada, United States, 89102

United States, New Mexico

Site 178; Not yet recruiting

Albuquerque, New Mexico, United States, 87109

United States, Ohio

Site 175; Recruiting

Westlake, Ohio, United States, 44145

United States, Texas

Site 120; Recruiting

Houston, Texas, United States, 77054

Site 172; Recruiting

Houston, Texas, United States, 77081

United States, Utah

Site 121; Recruiting

Draper, Utah, United States, 84020

Sponsors and Collaborators

Alto Neuroscience

Investigators

• Study Director: Adam Savitz, MD, PhD; Alto Neuroscience

More Information

• Responsible Party: Alto Neuroscience
• ClinicalTrials.gov Identifier: NCT05712187
• Other Study ID Numbers: ALTO-100-201
• First Posted: February 3, 2023
• Last Update Posted: March 22, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Additional relevant MeSH terms:

Depressive Disorder; Depression; Depressive Disorder, Major; Mood Disorders; Mental Disorders; Behavioral Symptoms