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

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

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

Interventions

• Drug MT1988 Low Dose
  Oral dosing MT1988; dose level 1
• Drug MT1988 High Dose
  Oral dosing MT1988; dose level 2
• Drug Placebo
  Oral Placebo; blinded to match MT1988 all doses

Primary outcome measures

• 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]
• 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]

Secondary outcome measures (12)

• Safety & tolerability as measured by number of treatment related adverse events [Time frame: Day 1 to Day 84]
• Safety & tolerability as measured by proportion of participants with treatment related adverse events [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 [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. [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. [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). [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). [Time frame: Day 28 and Day 56]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Basic science

Study locations

United States · 15 centers

• University of California, Irvine — Irvine
• University of California — Los Angeles
• University of California, San Francisco — San Francisco
• Yale University Conneticut Mental Health Center — New Haven
• Beth Israel Deaconess Medical Center — Boston
• Washington University — St Louis
• Northwell Health — Glen Oaks
• Columbia University — New York
• … and 7 more centers

Identifiers

NCT: NCT07226895 · AMP SCZ MT1988 / SCZ201 · U01MH137298 · U24MH137171

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗