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

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:

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

Study Overview

• Status: Recruiting
• Conditions: Clinical High Risk for Psychosis (CHR)
• Intervention / Treatment: Drug: MT1988 Low Dose; Drug: MT1988 High Dose; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Sheryl Caswell; Phone Number: +447539430768; Email: info@monumenttx.com

Study Locations

• United States
  • California
    • Irvine, California, United States, 92697
      • Not yet recruiting
      • University of California, Irvine
      • Contact: Jason Schiffman; Phone Number: 443-722-7768; Email: jason.schiffman@uci.edu
    • Los Angeles, California, United States, 90095
      • Not yet recruiting
      • University of California
      • Contact: Carrie Bearden; Phone Number: 925-642-1607
    • San Francisco, California, United States, 94107
      • Recruiting
      • University of California, San Francisco
      • Contact: Daniel Mathalon; Phone Number: 23860 415-221-4810; Email: daniel.mathalon@ucsf.edu
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Recruiting
      • Yale University Conneticut Mental Health Center
      • Contact: Scott Woods; Phone Number: 203-314-2088; Email: scott.woods@yale.edu
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Not yet recruiting
      • Beth Israel Deaconess Medical Center
      • Contact: William Stone; Phone Number: 508-740-2050; Email: wstone@bidmc.harvard.edu
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University
      • Contact: Daniel Mamah; Phone Number: 314-362-6952; Email: mamahd@wustl.edu
  • New York
    • Glen Oaks, New York, United States, 11004
      • Recruiting
      • Northwell Health
      • Contact: Ricardo Carrion; Phone Number: 718-470-8878; Email: RCarrion@northwell.edu
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University
      • Contact: Ragy Girgis; Phone Number: 646-774-5553; Email: ragy.girgis@nyspi.columbia.edu
      • Contact: Joshua Kantrowitz; Phone Number: 646-774-6738; Email: Joshua.kantrowitz@nyspi.columbia.edu
    • New York, New York, United States, 10128
      • Recruiting
      • Icahan School of Medicine at Mount Sinai
      • Contact: Cheryl Corcoran; Phone Number: 551-202-4342; Email: cheryl.corcoran@mssm.edu
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • Recruiting
      • University of North Carolina at Chapel Hill
      • Contact: Diana Perkins; Phone Number: 919-360-1602; Email: diana_perkins@med.unc.edu
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • Ohio State University
      • Contact: Nicholas Breitborde; Phone Number: 614-366-2449; Email: nicholas.breitborde@osumc.edu
  • Oregon
    • Eugene, Oregon, United States, 97403
      • Recruiting
      • Prevention Science Institute
      • Contact: Fred Sabb; Phone Number: 310-844-6458; Email: fws@uoregon.edu
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
      • Contact: Daniel Wolf; Phone Number: 215-662-3692; Email: danwolf@pennmedicine.upenn.edu
      • Contact: Christian Kohler; Email: kohler@pennmedicine.upenn.edu
    • Philadelphia, Pennsylvania, United States, 19122
      • Recruiting
      • Temple University
      • Contact: Lauren Ellman; Phone Number: 215-204-1571; Email: ellman@temple.edu
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • University of Pittsburgh School of Medicine
      • Contact: Leslie Horton; Phone Number: 412-864-7006; Email: hortonle2@upmc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Oral Placebo; blinded to match MT1988 all doses
Experimental: MT1988 Low Dose	Drug: MT1988 Low Dose; Oral dosing MT1988; dose level 1
Experimental: MT1988 High Dose	Drug: MT1988 High Dose; Oral dosing MT1988; dose level 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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		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	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	Day 56

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	Day 1 to Day 84
Change from baseline to week 4 in test of verbal memory (List learning task) as measured by PennCNB battery		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	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.		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.		Day 28 and Day 56
Change from baseline to weeks 4 and 8 in neurophysiology (EEG) as measured by mismatch negativity; auditory oddball P300.		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	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	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	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.	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.	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	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.	Day 28 and Day 56
Change from baseline to week 8 in biospecimen assays (levels of inflammation) as measured by blood samples (ELISA).		Day 56
Change from baseline to week 8 in cortisol levels, indicative of stress response, as measured by saliva collection (ELISA).		Day 56
Change from baseline to week 8 in physical/sedentary behavior as measured by a phone accelerometer and assessed by the mindLAMP app		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		Day -7 to Day 56
Change from baseline to week 8 in screen state (screen on/off timestamps) assessed by the mindLAMP app		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.	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.	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.	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.	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.	Day 56

Collaborators and Investigators

• Sponsor: Monument Therapeutics Limited
• Collaborators: National Institute of Mental Health (NIMH); Foundation for the National Institutes of Health; Accelerating Medicines Partnership (AMP)
• Investigators: Principal Investigator: Scott Woods, M.D., Yale University of Medicine; Principal Investigator: Martha E Shenton, PhD, Massachusetts General Brigham

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: October 24, 2025
• First Submitted That Met QC Criteria: November 6, 2025
• First Posted (Actual): November 12, 2025

Study Record Updates

• Last Update Posted (Actual): April 2, 2026
• Last Update Submitted That Met QC Criteria: April 1, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: AMP SCZ MT1988 / SCZ201; U01MH137298 (U.S. NIH Grant/Contract); U24MH137171 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No