Study of ALTO-300 in MDD

• ClinicalTrials.gov Identifier: NCT05922878
• Recruitment Status: Recruiting
• First Posted: June 28, 2023
• Last Update Posted: February 8, 2024
• Sponsor: Alto Neuroscience
• Information provided by (Responsible Party): Alto Neuroscience

Tracking Information

• First Submitted Date: May 26, 2023
• First Posted Date: June 28, 2023
• Last Update Posted Date: February 8, 2024
• Actual Study Start Date: June 8, 2023
• Estimated Primary Completion Date: July 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 19, 2023)

To assess efficacy of adjunctive ALTO-300 versus placebo on symptoms of MDD in a pre-defined subgroup of participants as measured by the change over time up to week 6 in the Montgomery-Åsberg Depression Rating Scale (MADRS). [ Time Frame: Change over time for up 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: Same as current

Current Secondary Outcome Measures (submitted: June 19, 2023)

• To assess efficacy of adjunctive ALTO-300 versus placebo on symptoms of MDD in all randomized participants as measured by the change over time up to week 6 in the Montgomery-Åsberg Depression Rating Scale (MADRS) [ Time Frame: Change over time for up 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 adjunctive ALTO-300 versus placebo for MDD as measured by the change over time up to week 6 in response (>50% improvement from baseline) rates based on the MADRS [ Time Frame: Change over time for up 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-300 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 14 ]
  Incidence, severity, and relatedness of Adverse Events
• To evaluate the safety of ALTO-300 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 14 ]
  Assessment of Heart Rate
• To evaluate the safety of ALTO-300 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 14 ]
  Assessment of Weight
• To evaluate the safety of ALTO-300 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 14 ]
  Assessment of Blood Pressure
• To evaluate the safety of ALTO-300 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 15 ]
  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: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of ALTO-300 in MDD
• Official Title: A Randomized, Double-Blind, Placebo-Controlled Study of ALTO-300 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-300 and placebo, used adjunctively to an antidepressant, related to patient characteristics.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Major Depressive Disorder

Intervention

• Drug: ALTO-300
  ALTO-300 capsule QD
• Drug: Placebo
  Placebo capsule QD

Study Arms

• Experimental: ALTO-300
  Participants will receive ALTO-300 capsule once daily in the evening, 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-300 capsule once daily in the evening from OL baseline until the end of OL period/early termination visit (Up to 8 weeks).
  Intervention: Drug: ALTO-300
• Placebo Comparator: Placebo
  Participants will receive matching placebo capsule once daily in the evening, from Day 1 to Day 42 in double blind (DB) treatment period.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 19, 2023): 200
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 2024
• Estimated Primary Completion Date: July 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Have a diagnosis of moderate to severe major depressive disorder (MDD)
• At Visit 2, currently taking a single SSRI, SNRI, 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
• Nightly use of sleep medication
• Diagnosed bipolar disorder, psychotic disorder, or dementia
• Current moderate or severe substance use disorder
• Has a history of hypersensitivity or allergic reaction to ALTO-300 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

• Sexes Eligible for Study: All

• Ages: 18 Years to 64 Years (Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Alto Neuroscience; 650-200-0412; clinical@altoneuroscience.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05922878
• Other Study ID Numbers: ALTO-300-201
• Has Data Monitoring Committee: No

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: Not Provided
• Current Responsible Party: Alto Neuroscience
• Original Responsible Party: Same as current
• Current Study Sponsor: Alto Neuroscience
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Alto Neuroscience
• Verification Date: February 2024