Major Depressive DisorderPhase 2NCT05922878
Study of ALTO-300 in MDD
A Phase 2 study testing ALTO-300 in people with Major Depressive Disorder, run by Alto Neuroscience at 75 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- ALTO-300
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 325 participants
- Where
- 75 sitesUnited States
- Study dates
- 8 Jun 2023to Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have a diagnosis of moderate to severe major depressive disorder (MDD)
- At Visit 1, currently taking a stable dose of 1 or 2 antidepressants (e.g., SSRI, SNRI, bupropion, or gepirone) for at least 6 weeks with no dose modifications in the past 2 weeks by Visit 2
- 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
- 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
Trial locations and contacts
75 sites in 1 country. Contact the study team or a site near you to ask about taking part.
75 sites in 1 country
United States75 sites, 31 recruiting
- Recruiting
Site 114
Albuquerque, New Mexico, 87108
- Terminated
Site 216
Allentown, Pennsylvania, 18104
- Recruiting
Site 316
Austin, Texas, 78712
- Recruiting
Site 218
Bellflower, California, 90706
- Withdrawn
Site 317
Blackfoot, Idaho, 83221
- Active, not recruiting
Site 119
Boise, Idaho, 83702
- Recruiting
Site 236
Boise, Idaho, 83704
- Active, not recruiting
Site 318
Carlsbad, California, 92009
- Active, not recruiting
Site 310
Chicago, Illinois, 60634
- Recruiting
Site 202
Cincinnati, Ohio, 45215
- Terminated
Site 159
Clermont, Florida, 34711
- Active, not recruiting
Site 207
Clinton, Utah, 84015
- Active, not recruiting
Site 203
Colorado Springs, Colorado, 80918
- Recruiting
Site 239
Conroe, Texas, 77384
- Withdrawn
Site 229
Creve Couer, Missouri, 63141
- Active, not recruiting
Site 102
Dallas, Texas, 75235
- Recruiting
Site 343
Denver, Colorado, 80209
- Active, not recruiting
Site 345
Evergreen, Colorado, 80439
- Active, not recruiting
Site 349
Evergreen, Colorado, 80439
- Recruiting
Site 277
Fairfax, Virginia, 22030
- Recruiting
Site 238
Fayetteville, Georgia, 30214
- Terminated
Site 347
Fort Worth, Texas, 76104
- Withdrawn
Site 148
Fort Worth, Texas, 76244
- Active, not recruiting
Site 217
Glendale, California, 91206
- Withdrawn
Site 279
Hattiesburg, Mississippi, 39401
- Active, not recruiting
Site 199
Hickory, North Carolina, 28601
- Recruiting
Site 275
Houston, Texas, 77007
- Recruiting
Site 320
Houston, Texas, 77050
- Active, not recruiting
Site 215
Jackson, Mississippi, 39216
- Recruiting
Site 335
Lafayette, California, 94549
- Recruiting
Site 335
Lafayette, California, 94596
- Recruiting
Site 344
Las Vegas, Nevada, 89102
- Active, not recruiting
Site 209
Los Angeles, California, 90064
- Recruiting
Site 240
Mankato, Minnesota, 56001
- Terminated
Site 201
Marrero, Louisiana, 70072
- Recruiting
Site 219
Mather, California, 95655
- Withdrawn
Site 350
Media, Pennsylvania, 19063
- Active, not recruiting
Site 225
Miami Gardens, Florida, 33014
- Active, not recruiting
Site 190
Miami Lakes, Florida, 33016
- Recruiting
Site 265
Minneapolis, Minnesota, 55455
- Terminated
Site 194
Mission Viejo, California, 92691
- Withdrawn
Site 206
Missouri City, Texas, 77459
- Terminated
Site 198
Monroe, Louisiana, 71201
- Recruiting
Site 267
Moorpark, California, 93012
- Active, not recruiting
Site 352
Moosic, Pennsylvania, 18507
- Recruiting
Site 283
New York, New York, 10036
- Active, not recruiting
Site 319
New York, New York, 10036
- Withdrawn
Site 214
Norwalk, Connecticut, 06851
- Active, not recruiting
Site 161
Okeechobee, Florida, 34972
- Terminated
Site 195
Oklahoma City, Oklahoma, 73112
- Withdrawn
Site 303
Oklahoma City, Oklahoma, 73120
- Active, not recruiting
Site 231
Omaha, Nebraska, 68144
- Recruiting
Site 200
Phoenix, Arizona, 85012
- Withdrawn
Site 189
Phoenix, Arizona, 85021
- Recruiting
Site 353
Plano, Texas, 75093
- Active, not recruiting
Site 315
Provo, Utah, 84604
- Terminated
Site 196
Richmond, Texas, 77407
- Active, not recruiting
Site 211
Roanoke, Virginia, 24018
- Terminated
Site 191
Rochester, New York, 14618
- Recruiting
Site 193
Rogers, Arkansas, 72758
- Recruiting
Site 287
Rose Hill, North Carolina, 28458
- Recruiting
Site 234
San Marcos, Texas, 78666
- Active, not recruiting
Site 224
Savannah, Georgia, 31405
- Terminated
Site 208
Snellville, Georgia, 30078
- Recruiting
Site 264
St Louis, Missouri, 63304
- Terminated
Site 192
Staten Island, New York, 10314
- Recruiting
Site 235
Stephenville, Texas, 76401
- Not yet recruiting
Site 293
Stone Mountain, Georgia, 30083
- Recruiting
Site 221
Tampa, Florida, 33629
- Recruiting
Site 197
Temecula, California, 92591
- Active, not recruiting
Site 220
West Palm Beach, Florida, 33407
- Active, not recruiting
Site 314
Wichita, Kansas, 67214
- Recruiting
Site 268
Winston-Salem, North Carolina, 27103
- Recruiting
Site 288
Worcester, Massachusetts, 01608
- Active, not recruiting
Site 187
Yuma, Arizona, 85364
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled Study of ALTO-300 With an Open-Label Extension in Adults With Major Depressive Disorder
The purpose of this study is to determine efficacy differences between ALTO-300 and placebo, used adjunctively to an antidepressant, related to patient characteristics.
- Conditions
- Major Depressive Disorder
- Being tested
- ALTO-300, 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-300Drug
ALTO-300 capsule QD
PlaceboDrug
Placebo capsule QD
| Study group | Role | What they receive |
|---|---|---|
| ALTO-300 | Experimental | Participants will receive ALTO-300 25mg 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). Receives: Drug: ALTO-300 |
| Placebo | Placebo comparator | Participants will receive matching placebo capsule once daily in the evening, 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 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).
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 over time for up to week 6
Secondary outcomes (7)
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)
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 over time for up to week 6
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
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 over time for up to week 6
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.
Incidence, severity, and relatedness of Adverse Events
Measured: Assessed from Day 1 to Week 14
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.
Assessment of Heart Rate
Measured: Assessed from Day 1 to Week 14
To evaluate the safety of ALTO-300 during both the OL and DB periods of the study as measured by the assessment of Weight.
Assessment of Weight Change
Measured: Assessed from Day 1 to Week 14
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.
Assessment of Blood Pressure
Measured: Assessed from Day 1 to Week 14
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).
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 15
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2023
- Study start8 Jun 2023
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
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
- 325 participants (estimated)
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
- NCT05922878
- Sponsor's protocol ID
- ALTO-300-201
- Status last verified
- Oct 2026
- First submitted
- 26 May 2023
- Last updated
- 26 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled Study of ALTO-300 With an Open-Label Extension in Adults With Major Depressive Disorder
- ClinicalTrials.gov ID
- NCT05922878
- Acronym / sponsor ID
- ALTO-300-201
- Conditions
- Major Depressive Disorder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 325 participants (estimated)
- Lead sponsor
- Alto NeuroscienceIndustry (pharma, biotech, devices)
- Study start
- 8 Jun 2023 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 28 Jun 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-300 and placebo, used 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-300 | Experimental | Drug: ALTO-300Participants will receive ALTO-300 25mg 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). |
| Placebo | Placebo comparator | Drug: PlaceboParticipants will receive matching placebo capsule once daily in the evening, from Day 1 to Day 42 in double blind (DB) treatment period. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Have a diagnosis of moderate to severe major depressive disorder (MDD)
- At Visit 1, currently taking a stable dose of 1 or 2 antidepressants (e.g., SSRI, SNRI, bupropion, or gepirone) for at least 6 weeks with no dose modifications in the past 2 weeks by Visit 2
- 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 (6 listed)
- 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
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-300ALTO-300 capsule QD | Drug | ALTO-300 |
| PlaceboPlacebo capsule QD | Drug | Placebo |
Primary outcome
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.
7 secondary outcomes
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
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
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
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
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
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
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2026.
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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.
Adam Savitz, MD, PhD study director
Alto Neuroscience
75 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-300 in people with Major Depressive Disorder, run by Alto Neuroscience at 75 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 6 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: looking for participants now, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 75 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Alto Neuroscience (650-200-0412, clinical@altoneuroscience.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). 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 26 Oct 2026.