Major Depressive DisorderPhase 2NCT05712187
Phase 2b Study of ALTO-100 in MDD
A Phase 2 study testing ALTO-100 in people with Major Depressive Disorder, run by Alto Neuroscience at 34 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- ALTO-100
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 301 participants
- Where
- 34 sitesUnited States
- Study dates
- 10 Jan 2023to 24 Oct 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
34 sites in 1 country.
34 sites in 1 country
United States34 sites
Site 178
Albuquerque, New Mexico, 87109
Site 151
Baltimore, Maryland, 21229
Site 174
Birmingham, Alabama, 35294
Site 184
Brooklyn, New York, 11229
Site 186
Brooksville, Florida, 34613
Site 137
Carmel, Indiana, 46032
Site 185
Centennial, Colorado, 80112
Site 136
Chandler, Arizona, 85226
Site 141
Costa Mesa, California, 92626
Site 121
Draper, Utah, 84020
Site 147
Fort Worth, Texas, 76104
Site 118
Fresno, California, 93703
Site 120
Houston, Texas, 77054
Site 172
Houston, Texas, 77081
Site 173
Huntsville, Alabama, 35801
Site 181
Imperial, California, 92251
Site 108
Jackson, Mississippi, 39216
Site 171
Jackson, Mississippi, 39216
Site 204
Jacksonville, Florida, 32256
Site 144
Las Vegas, Nevada, 89102
Site 142
Lincoln, Nebraska, 68562
Site 139
Little Rock, Arkansas, 72211
Site 183
Memphis, Tennessee, 38119
Site 180
New York, New York, 10022
Site 210
New York, New York, 10128
Site 157
North Charleston, South Carolina, 29405
Site 182
Oceanside, California, 92056
Site 188
Oceanside, California, 92056
Site 205
Orlando, Florida, 32801
Site 179
Rancho Cucamonga, California, 91730
Site 116
Sacramento, California, 95655
Site 212
Tampa, Florida, 33629
Site 213
Tampa, Florida, 33629
Site 175
Westlake, Ohio, 44145
About this study
Official title: 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.
- Conditions
- Major Depressive Disorder
- Being tested
- ALTO-100, Placebo
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ALTO-100Drug
ALTO-100 tablet BID
PlaceboDrug
Placebo tablet BID
| Study group | Role | What they receive |
|---|---|---|
| ALTO-100 | Experimental | 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). Receives: Drug: ALTO-100 |
| Placebo DB | Placebo comparator | Participants will receive matching placebo tablet twice daily, from Day 1 to Day 42 in double blind (DB) treatment period. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Change assessed from Day 1 to Week 6
Secondary outcomes (10)
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.
Measured: 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.
Measured: 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 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Assessed from Day 1 to Week 13
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2023
- Study start10 Jan 2023
- Primary completion5 Sep 2024
- Study completion24 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 301 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alto Neuroscience
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Adam Savitz, MD, PhD, Study director, Alto Neuroscience
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05712187
- Sponsor's protocol ID
- ALTO-100-201
- Status last verified
- Jul 2024
- First submitted
- 24 Dec 2022
- Last updated
- 8 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled Study of ALTO-100 With an Open-Label Extension in Adults With Major Depressive Disorder
- ClinicalTrials.gov ID
- NCT05712187
- Acronym / sponsor ID
- ALTO-100-201
- Conditions
- Major Depressive Disorder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 301 participants (actual)
- Lead sponsor
- Alto NeuroscienceIndustry (pharma, biotech, devices)
- Study start
- 10 Jan 2023 (actual)
- Primary completion
- 5 Sep 2024 (actual)
- Study completion
- 24 Oct 2024 (actual)
- First posted
- 3 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ALTO-100 | Experimental | Drug: ALTO-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 DB | Placebo comparator | Drug: PlaceboParticipants will receive matching placebo tablet twice daily, from Day 1 to Day 42 in double blind (DB) treatment period. |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ALTO-100ALTO-100 tablet BID | Drug | ALTO-100 |
| PlaceboPlacebo tablet BID | Drug | Placebo DB |
Primary outcome
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.
10 secondary outcomes
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
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
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
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
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
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
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
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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2025.
- Individual participant dataSharing planned: No
Related trials for Major Depressive Disorder
Not yet recruiting
Preventive and Personalized Digital Emotion Regulation Skills Intervention to Reduce Depression and Anxiety in Youths With Adverse Childhood Experiences
Adverse Childhood Experience, Depression / Major Depressive Disorder
RecruitingPhase 4
Biomarker-Guided Antidepressant Selection
Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)
Recruiting
Targeting Network Dysfunction in Apathy of Late-life Depression Using Digital Therapeutics
Major Depressive Disorder, Apathy
RecruitingObservational study
Student Precarity and Psychiatry
Depressive Disorder, Major, Generalized Anxiety Disorder
Not yet recruiting
Acute Intermittent Hypoxia Therapy for Depression
Major Depressive Disorder (MDD)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adam Savitz, MD, PhD study director
Alto Neuroscience
34 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ALTO-100 in people with Major Depressive Disorder, run by Alto Neuroscience at 34 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 34 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Sep 2025.