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

Phase 2Not Yet RecruitingNCT07226895

Monument Therapeutics Limited150 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

QUADRUPLE

Enrollment

150

Conditions

Clinical High Risk for Psychosis (CHR)

Interventions

Eligibility

Sex: ALLMin age: 17 YearsMax age: 30 Years

Medical Language ↔ Plain English

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.

Locations (15)

University of California, Irvine

Irvine, California, United States

University of California

Los Angeles, California, United States

University of California, San Francisco

San Francisco, California, United States

Yale University Conneticut Mental Health Center

New Haven, Connecticut, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Washington University

St Louis, Missouri, United States

Northwell Health

Glen Oaks, New York, United States

Columbia University

New York, New York, United States

Icahan School of Medicine at Mount Sinai

New York, New York, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

...and 5 more locations

Outcomes

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

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

Time frame: 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

Time frame: Day 56

Secondary Outcomes

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

Time frame: 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

Time frame: Day 1 to Day 84

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

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

Time frame: 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.

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

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

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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.

Time frame: Day 28 and Day 56

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.

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.

Time frame: 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.

Time frame: 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.

Time frame: Day 56

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

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

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

Overview

Conditions

Interventions

Eligibility

Locations (15)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts