Recruiting

NCT Number: NCT07226895

A Study Exploring Changes in a Variety of Biomarkers Following Dosing With MT1988 in Participants at Clinical High Risk 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:

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

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Key information

Conditions

Clinical High Risk for Psychosis (CHR)

Age range

17 year–30 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

University of California, Irvine, Irvine, California, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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.

Exclusion criteria

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.

Treatment and study plan

MT1988 Low Dose

Drug

Oral dosing MT1988; dose level 1

MT1988 High Dose

Drug

Oral dosing MT1988; dose level 2

Placebo

Drug

Oral Placebo; blinded to match MT1988 all doses

Primary outcomes

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

Time frame: Day 56
Change from baseline to week 8 in attenuated positive symptoms as measured by PSYCHS-CT total score

Time frame: Day 56

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
Change from baseline to week 8 in negative symptoms as measured by the Negative Symptom Inventory - Psychosis Risk (NSI-PR) total score

Time frame: Day 56

Total score of 0-44 across 11 domains; where a higher score indicates more severe symptoms

Secondary outcomes

Safety & tolerability as measured by number of treatment related adverse events

Time frame: Day 1 to Day 84

The total number of treatment related adverse events reported per study arm (high dose MT1988, low dose MT1988, placebo) will be compared
Safety & tolerability as measured by proportion of participants with treatment related adverse events

Time frame: Day 1 to Day 84

The proportion of participants in each study arm (high dose MT1988, low dose MT1988, placebo) experiencing treatment related adverse events will be compared
Change from baseline to week 4 in test of verbal memory (List learning task) as measured by PennCNB battery

Time frame: Day 28
Change from baseline to weeks 4 and 8 in overall composite score of cognitive performance as measured by PennCNB test battery

Time frame: Day 28 and Day 56

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
Change from baseline to weeks 4 and 8 in a cognitive test of working memory and executive function as measured by CANTAB SWM test.

Time frame: 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.

Time frame: Day 28 and Day 56
Change from baseline to weeks 4 and 8 in neurophysiology (EEG) as measured by mismatch negativity; auditory oddball P300.

Time frame: Day 28 and Day 56
Change from baseline to week 4 in attenuated positive symptoms, as measured by the PSYCHS-CT total score.

Time frame: Day 28

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
Change from baseline to week 4 in negative symptoms as measured by the NSI-PR total score.

Time frame: Day 28

Total score of 0-44 across 11 domains; where a higher score indicates more severe symptoms
Change from baseline to weeks 4 and 8 in overall psychopathology as measured by the Positive And Negative Symptoms Scale (PANSS) total score.

Time frame: Day 28 and Day 56

Total PANSS score between 30 and 120; where a higher score indicates more severe symptoms
Change from baseline to weeks 4 and 8 in symptoms of anxiety as measured by the Overall Anxiety Severity and Impairment Scale (OASIS).

Time frame: Day 28 and Day 56

The OASIS (Overall Anxiety Severity and Impairment Scale) ranges from 0 to 20. Higher scores indicate greater severity and impairment due to anxiety symptoms.
Change from baseline to weeks 4 and 8 in symptoms of depression as measured by the Calgary Depression Scale for Schizophrenia (CDSS).

Time frame: Day 28 and Day 56

The Calgary Depression Scale for Schizophrenia (CDSS) ranges from 0 to 27. Higher scores indicate more severe depressive symptoms in individuals with schizophrenia.
Change from baseline to weeks 4 and 8 in symptoms of stress as measured by the Perceived Stress Scale (PSS).

Time frame: Day 28 and Day 56

The Perceived Stress Scale (PSS) ranges from 0 to 40. Higher scores indicate greater levels of perceived stress
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).

Time frame: Day 28 and Day 56

The PROMIS-SD scale ranges from 8 to 40. Higher scores indicate greater severity of recent sleep disturbance.
Change from baseline to week 8 in biospecimen assays (levels of inflammation) as measured by blood samples (ELISA).

Time frame: Day 56
Change from baseline to week 8 in cortisol levels, indicative of stress response, as measured by saliva collection (ELISA).

Time frame: Day 56
Change from baseline to week 8 in physical/sedentary behavior as measured by a phone accelerometer and assessed by the mindLAMP app

Time frame: 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

Time frame: Day -7 to Day 56
Change from baseline to week 8 in screen state (screen on/off timestamps) assessed by the mindLAMP app

Time frame: 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.

Time frame: Day 28 and Day 56

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.
Correlation between latent inhibition score and cognitive change from baseline to weeks 4 and 8 as measured by CANTAB RVP.

Time frame: Day 28 and Day 56

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.
Correlation between the polygenic risk score (as measured by plasma isolated-DNA samples) and PennCNB score change at week 8.

Time frame: Day 56

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.
Correlation between the polygenic risk score (as measured by plasma isolated-DNA samples) and PYSCHS-CT score change at week 8.

Time frame: Day 56

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.
Correlation between the polygenic risk score (as measured by plasma isolated-DNA samples) and NSI-PR score change at week 8.

Time frame: Day 56

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.

Study contacts

Contact information is provided by the study sponsor or research team.

Sheryl Caswell

CONTACT

[email protected]

+447539430768

Sponsors and collaborators

Lead sponsor

Monument Therapeutics Limited

Industry

Collaborators

Accelerating Medicines Partnership (AMP)
Foundation for the National Institutes of Health
National Institute of Mental Health (NIMH)

Registry information

Official study 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

Important dates

Study start: 2026
Primary completion: 2027
Study completion: 2027
First posted: Nov 12, 2025
Registry last updated: Jun 8, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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Key information

Conditions

Age range

Sex eligibility

Study type

Phase

Primary location

Who can participate

Treatment and study plan

MT1988 Low Dose

MT1988 High Dose

Placebo

Primary outcomes

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

Change from baseline to week 8 in attenuated positive symptoms as measured by PSYCHS-CT total score

Change from baseline to week 8 in negative symptoms as measured by the Negative Symptom Inventory - Psychosis Risk (NSI-PR) total score

Secondary outcomes

Safety & tolerability as measured by number of treatment related adverse events

Safety & tolerability as measured by proportion of participants with treatment related adverse events

Change from baseline to week 4 in test of verbal memory (List learning task) as measured by PennCNB battery

Change from baseline to weeks 4 and 8 in overall composite score of cognitive performance as measured by PennCNB test battery

Change from baseline to weeks 4 and 8 in a cognitive test of working memory and executive function as measured by CANTAB SWM test.

Change from baseline to weeks 4 and 8 in a cognitive test of sustained attention as measured by CANTAB RVP test.

Change from baseline to weeks 4 and 8 in neurophysiology (EEG) as measured by mismatch negativity; auditory oddball P300.

Change from baseline to week 4 in attenuated positive symptoms, as measured by the PSYCHS-CT total score.

Change from baseline to week 4 in negative symptoms as measured by the NSI-PR total score.

Change from baseline to weeks 4 and 8 in overall psychopathology as measured by the Positive And Negative Symptoms Scale (PANSS) total score.

Change from baseline to weeks 4 and 8 in symptoms of anxiety as measured by the Overall Anxiety Severity and Impairment Scale (OASIS).

Change from baseline to weeks 4 and 8 in symptoms of depression as measured by the Calgary Depression Scale for Schizophrenia (CDSS).

Change from baseline to weeks 4 and 8 in symptoms of stress as measured by the Perceived Stress Scale (PSS).

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).

Change from baseline to week 8 in biospecimen assays (levels of inflammation) as measured by blood samples (ELISA).

Change from baseline to week 8 in cortisol levels, indicative of stress response, as measured by saliva collection (ELISA).

Change from baseline to week 8 in physical/sedentary behavior as measured by a phone accelerometer and assessed by the mindLAMP app

Change from baseline to week 8 in roaming/movement behavior as measured by a phone GPS and assessed by the mindLAMP app

Change from baseline to week 8 in screen state (screen on/off timestamps) assessed by the mindLAMP app

Correlation between latent inhibition score and cognitive change from baseline to weeks 4 and 8 as measured by CANTAB SWM.

Correlation between latent inhibition score and cognitive change from baseline to weeks 4 and 8 as measured by CANTAB RVP.

Correlation between the polygenic risk score (as measured by plasma isolated-DNA samples) and PennCNB score change at week 8.

Correlation between the polygenic risk score (as measured by plasma isolated-DNA samples) and PYSCHS-CT score change at week 8.

Correlation between the polygenic risk score (as measured by plasma isolated-DNA samples) and NSI-PR score change at week 8.

Study contacts

Sponsors and collaborators

Lead sponsor

Collaborators

Registry information

Official study title

Important dates

Related clinical trials

French Validation of Schizophrenia Proneness Instrument- Child Youth

Experience of UHR and PEP Individuals During Mindfulness: a Qualitative Phenomenological Study

Telehealth Cognitive Behavioral Therapy for Youth at Risk for Psychosis

Interventions for Clinical High Risk Youth in Tunisia