Clinical High Risk for Psychosis (CHR)Phase 1/2NCT07226895
A Study Exploring Changes in a Variety of Biomarkers Following Dosing With MT1988 in Participants at Clinical High Risk for Psychosis
A Phase 1/2 study testing MT1988 Low Dose and MT1988 High Dose in people with Clinical High Risk for Psychosis (CHR), run by Monument Therapeutics Limited at 15 sites in United States.
Trial summary
The goal of this clinical trial is to learn how tests undertaken by people at high risk of developing psychosis (aged 17 to 30 years old) change when those people are given the study drug MT1988 daily for 8 weeks. Read more about this study
- Who is it for?
- Ages 17 to 30 years
- Conditions the study is for
- Clinical High Risk for Psychosis (CHR)
- What is being tested?
- MT1988 Low Dose and MT1988 High Dose
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 15 sitesUnited States
- Study dates
- 3 Mar 2026to Oct 2027
- Phase
- Phase 1/2
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 17 to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Aged 17 to 30 years at time of consent.
- Capacity to provide informed consent. (For patients under 17 years, participants must assent and informed consent provided by one parent or legal guardian).
- Meet diagnostic criteria for Clinical High Risk of Psychosis (CHR).
- For females of reproductive potential - not pregnant or nursing and willing to comply with contraceptive requirements.
Who cannot join
- Clinically significant medical disorder or laboratory test abnormality at Day 1.
- History of or current condition which may prevent participant from complying with study procedures.
- Past or current schizophrenia, other disorder with symptoms of psychosis, major cognitive disorder resulting from traumatic brain injury.
- Received antipsychotic medication equivalent to a total lifetime haloperidol dose >50 mg.
- Current use of medications which could interfere with the study endpoints - to be assessed by the Investigator at screening.
- Unable to abstain from nicotine (e.g. cigarettes, vape) for two hours before cognitive testing.
- Unable to abstain from marijuana use on test day prior to test completion.
- History of suicide attempt or behavior in previous 12 months, or risk of suicidal behavior during the study.
Trial locations and contacts
15 sites in 1 country. Contact the study team or a site near you to ask about taking part.
15 sites in 1 country
United States15 sites, 15 recruiting
- Recruiting
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02115
William Stone, 508-740-2050, wstone@bidmc.harvard.edu
- Recruiting
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27514
Diana Perkins, 877-774-6319, PRIME@med.unc.edu
- Recruiting
Ohio State University
Columbus, Ohio, 43210
Nicholas Breitborde, 614-398-2991, nicholas.breitborde@osumc.edu
- Recruiting
Prevention Science Institute
Eugene, Oregon, 97403
Fred Sabb, 310-844-6458, fws@uoregon.edu
- Recruiting
Northwell Health
Glen Oaks, New York, 11004
Ricardo Carrion, 347-502-1909, RCarrion@northwell.edu
- Recruiting
University of California, Irvine
Irvine, California, 92697
Jason Schiffman, 443-722-7768, jason.schiffman@uci.edu
- Recruiting
University of California
Los Angeles, California, 90095
Carrie Bearden, 310-206-3466, cbearden@mednet.ucla.edu
- Recruiting
Yale University Conneticut Mental Health Center
New Haven, Connecticut, 06519
Scott Woods, 203-200-8997, scott.woods@yale.edu
Munaza Ali, 203-200-8997, munaza.ali@yale.edu
- Recruiting
Columbia University
New York, New York, 10032
Ragy Girgis, 646-774-5553, ragy.girgis@nyspi.columbia.edu
Joshua Kantrowitz, 646-774-6738, Joshua.kantrowitz@nyspi.columbia.edu
- Recruiting
Icahan School of Medicine at Mount Sinai
New York, New York, 10128
Cheryl Corcoran, 212-659-1671, cheryl.corcoran@mssm.edu
- Recruiting
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Daniel Wolf, 215-662-3692, danwolf@pennmedicine.upenn.edu
Christian Kohler, kohler@pennmedicine.upenn.edu
- Recruiting
Temple University
Philadelphia, Pennsylvania, 19122
Lauren Ellman, 215-204-1571, ellman@temple.edu
- Recruiting
University of Pittsburgh School of Medicine
Pittsburgh, Pennsylvania, 15213
Leslie Horton, 412-864-7006, hortonle2@upmc.edu
- Recruiting
University of California, San Francisco
San Francisco, California, 94107
Daniel Mathalon, 415-221-4810 ext. 23860, daniel.mathalon@ucsf.edu
- Recruiting
Washington University
St Louis, Missouri, 63110
Daniel Mamah, 314-273-4329, mamahd@wustl.edu
Malana Kanallakan, 314-273-4329, malana@wustl.edu
About this study
Official title: A Study to Explore Changes in Cognitive, Clinical, Biological and Digital Measures Following 8 Weeks of Twice-daily Dosing of MT1988 and to Evaluate Safety & Tolerability of MT1988, in Participants at Clinical High Risk (CHR) for Psychosis
The goal of this clinical trial is to learn how tests undertaken by people at high risk of developing psychosis (aged 17 to 30 years old) change when those people are given the study drug MT1988 daily for 8 weeks. This will help identify tests that could be used in later trials developing treatments for symptoms in people at high risk of developing psychosis, to measure whether those new treatments are effective.
The main question this trial aims to answer is:
Read more
Can any of the tests (biomarkers) used in this study detect changes in participants dosed with one of two different dose levels of MT1988?
Researchers will compare the results from two dose levels of MT1988 to a placebo group. Researchers do not expect to see the test results change in participants taking placebo and this will be compared to changes expected in test results in participants taking MT1988.
Participants will:
- take a dose of MT1988 or placebo twice per day for 8 weeks
- attend clinic appointments every two weeks to undertake assessments
- report any side effects they experience to the researchers
- Conditions
- Clinical High Risk for Psychosis (CHR)
- Being tested
- MT1988 Low Dose, MT1988 High Dose, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MT1988 Low DoseDrug
Oral dosing MT1988; dose level 1
MT1988 High DoseDrug
Oral dosing MT1988; dose level 2
PlaceboDrug
Oral Placebo; blinded to match MT1988 all doses
| Study group | Role | What they receive |
|---|---|---|
| MT1988 Low Dose | Experimental | Not described Receives: Drug: MT1988 Low Dose |
| MT1988 High Dose | Experimental | Not described Receives: Drug: MT1988 High Dose |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline to week 8 in test of verbal memory (List Learning Task) as measured by the Penn Computerized Neurobehavioral Battery (PennCNB) test battery
Measured: Day 56
Change from baseline to week 8 in attenuated positive symptoms as measured by PSYCHS-CT total score
PSYCHS-CT: Positive Symptoms and Diagnostic Criteria for the Comprehensive Assessment of At-Risk Mental States (CAARMS) Harmonized with the Structured Interview for Pyschosis-risk Syndromes (SIPS) - Clinical Trials version.
Total score of 0-90 across maximum 15 domain; where a higher score indicates more severe symptoms
Measured: Day 56
Change from baseline to week 8 in negative symptoms as measured by the Negative Symptom Inventory - Psychosis Risk (NSI-PR) total score
Total score of 0-44 across 11 domains; where a higher score indicates more severe symptoms
Measured: Day 56
Secondary outcomes (24)
Safety & tolerability as measured by number of treatment related adverse events
The total number of treatment related adverse events reported per study arm (high dose MT1988, low dose MT1988, placebo) will be compared
Measured: Day 1 to Day 84
Safety & tolerability as measured by proportion of participants with treatment related adverse events
The proportion of participants in each study arm (high dose MT1988, low dose MT1988, placebo) experiencing treatment related adverse events will be compared
Measured: Day 1 to Day 84
Change from baseline to week 4 in test of verbal memory (List learning task) as measured by PennCNB battery
Measured: Day 28
Change from baseline to weeks 4 and 8 in overall composite score of cognitive performance as measured by PennCNB test battery
Composite includes Continuous Performance Test, Fractal N-Back, Digit-Symbol Substitution Test, Digit Symbol Recall, Visual Object Learning Test, Emotion Recognition Test, Finger Tapping Test, Motor Praxis
Measured: Day 28 and Day 56
Change from baseline to weeks 4 and 8 in a cognitive test of working memory and executive function as measured by CANTAB SWM test.
Measured: Day 28 and Day 56
Change from baseline to weeks 4 and 8 in a cognitive test of sustained attention as measured by CANTAB RVP test.
Measured: Day 28 and Day 56
Change from baseline to weeks 4 and 8 in neurophysiology (EEG) as measured by mismatch negativity; auditory oddball P300.
Measured: Day 28 and Day 56
Change from baseline to week 4 in attenuated positive symptoms, as measured by the PSYCHS-CT total score.
PSYCHS-CT: Positive Symptoms and Diagnostic Criteria for the Comprehensive Assessment of At-Risk Mental States (CAARMS) Harmonized with the Structured Interview for Pyschosis-risk Syndromes (SIPS) - Clinical Trials version.
Total score of 0-90 across maximum 15 domain; where a higher score indicates more severe symptoms
Measured: Day 28
Change from baseline to week 4 in negative symptoms as measured by the NSI-PR total score.
Total score of 0-44 across 11 domains; where a higher score indicates more severe symptoms
Measured: Day 28
Change from baseline to weeks 4 and 8 in overall psychopathology as measured by the Positive And Negative Symptoms Scale (PANSS) total score.
Total PANSS score between 30 and 120; where a higher score indicates more severe symptoms
Measured: Day 28 and Day 56
Change from baseline to weeks 4 and 8 in symptoms of anxiety as measured by the Overall Anxiety Severity and Impairment Scale (OASIS).
The OASIS (Overall Anxiety Severity and Impairment Scale) ranges from 0 to 20. Higher scores indicate greater severity and impairment due to anxiety symptoms.
Measured: Day 28 and Day 56
Change from baseline to weeks 4 and 8 in symptoms of depression as measured by the Calgary Depression Scale for Schizophrenia (CDSS).
The Calgary Depression Scale for Schizophrenia (CDSS) ranges from 0 to 27. Higher scores indicate more severe depressive symptoms in individuals with schizophrenia.
Measured: Day 28 and Day 56
Change from baseline to weeks 4 and 8 in symptoms of stress as measured by the Perceived Stress Scale (PSS).
The Perceived Stress Scale (PSS) ranges from 0 to 40. Higher scores indicate greater levels of perceived stress
Measured: Day 28 and Day 56
Change from baseline to weeks 4 and 8 in sleep disturbance as measured by the Patient-Reported Outcomes Measurement Information System - Sleep Disturbance (PROMIS-SD).
The PROMIS-SD scale ranges from 8 to 40. Higher scores indicate greater severity of recent sleep disturbance.
Measured: Day 28 and Day 56
Change from baseline to week 8 in biospecimen assays (levels of inflammation) as measured by blood samples (ELISA).
Measured: Day 56
Change from baseline to week 8 in cortisol levels, indicative of stress response, as measured by saliva collection (ELISA).
Measured: Day 56
Change from baseline to week 8 in physical/sedentary behavior as measured by a phone accelerometer and assessed by the mindLAMP app
Measured: Day -7 to Day 56
Change from baseline to week 8 in roaming/movement behavior as measured by a phone GPS and assessed by the mindLAMP app
Measured: Day -7 to Day 56
Change from baseline to week 8 in screen state (screen on/off timestamps) assessed by the mindLAMP app
Measured: Day -7 to Day 56
Correlation between latent inhibition score and cognitive change from baseline to weeks 4 and 8 as measured by CANTAB SWM.
The data will be explored to determine whether the score on the latent inhibition assessment tool ("positive", "negative") correlates with cognitive change from baseline to weeks 4 and 8 as measured by CANTAB SWM, using Pearson's correlation coefficient.
Measured: Day 28 and Day 56
Correlation between latent inhibition score and cognitive change from baseline to weeks 4 and 8 as measured by CANTAB RVP.
The data will be explored to determine whether the score on the latent inhibition assessment tool ("positive", "negative") correlates with cognitive change from baseline to weeks 4 and 8 as measured by CANTAB RVP, using Pearson's correlation coefficient.
Measured: Day 28 and Day 56
Correlation between the polygenic risk score (as measured by plasma isolated-DNA samples) and PennCNB score change at week 8.
Polygenic risk scores serve to modestly improve psychosis risk prediction. The data will be examined for correlation between individual genetic risk prediction for psychosis and any changes between baseline and Day 56 for each individual biomarker, using Pearson's correlation coefficient.
Measured: Day 56
Correlation between the polygenic risk score (as measured by plasma isolated-DNA samples) and PYSCHS-CT score change at week 8.
Polygenic risk scores serve to modestly improve psychosis risk prediction. The data will be examined for correlation between individual genetic risk prediction for psychosis and any changes between baseline and Day 56 for each individual biomarker, using Pearson's correlation coefficient.
Measured: Day 56
Correlation between the polygenic risk score (as measured by plasma isolated-DNA samples) and NSI-PR score change at week 8.
Polygenic risk scores serve to modestly improve psychosis risk prediction. The data will be examined for correlation between individual genetic risk prediction for psychosis and any changes between baseline and Day 56 for each individual biomarker, using Pearson's correlation coefficient.
Measured: Day 56
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2025
- Study start3 Mar 2026
- Primary completionSep 2027 (estimated)
- Study completionOct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Clinical High Risk for Psychosis (CHR)Studies 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 1/2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Monument Therapeutics Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Institute of Mental Health (NIMH), Foundation for the National Institutes of Health, Accelerating Medicines Partnership (AMP)
- Responsible party
- Sponsor
- Investigators
- Scott Woods, M.D., Principal investigator, Yale University of MedicineMartha E Shenton, PhD, Principal investigator, Massachusetts General Brigham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07226895
- Sponsor's protocol ID
- AMP SCZ MT1988 / SCZ201
- Other IDs
- U01MH137298, U24MH137171
- Status last verified
- Jun 2026
- First submitted
- 24 Oct 2025
- Last updated
- 8 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All clinical and phenotypic data will be shared with the NIMH National Data Archive (NDA). All data will be de-identified prior to receipt by the NDA, but the information needed to generate a global unique identifier for the NDA will be collected for each participant. Phenotypic and clinical data will be collected and deposited in the NDA using the data dictionaries available in NDA. Audio files will be transcribed using HIPAA-compliant services. Only pseudo-anonymized transcripts will be sent to the NDA.