Notice of Intent to Publish a Funding Opportunity Announcement for Clinical High Risk for Psychosis Clinical Trial Network (U01 Clinical Trial Required)

Key Dates

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National Institute of Mental Health (NIMH)

The purpose of this Notice is to alert the community that the National Institute of Mental Health intends to publish a Funding Opportunity Announcement (FOA) to support one or more clinical trial networks to evaluate biological and clinical outcome measures in individuals at clinical high risk (CHR) for psychosis in Proof of Principle (PoP) trials using pharmacological interventions. Unique drug development tools generated through the Accelerating Medicines Partnership Schizophrenia (AMP SCZ) initiative will be validated in the PoP trials.

This Notice is being provided to allow potential applicants sufficient time to develop meaningful collaborations and responsive projects. The FOA is expected to be published in May 2023 with an expected application due date in Fall 2023.

This FOA will utilize the U01 activity code. Details of the planned FOA are provided below.

This Notice encourages investigators with expertise and insights in leading clinical trials related to CHR for psychosis and/or schizophrenia to begin to consider applying to this new FOA. 

Background

Given the highly disruptive and disabling nature of psychotic disorders, early intervention has been recommended as a means of preventing psychosis onset among individuals at clinical high risk (CHR). Although many molecular targets have been identified as having therapeutic potential in the CHR population, testing the efficacy of such therapeutics at the CHR stage has been hampered by low and variable rates of conversion to psychosis, lack of biomarkers that reliably predict progression, and heterogeneous clinical outcomes for CHR syndrome, including anxiety, depression, and substance use disorders. The AMP SCZ initiative launched in 2020 as an international collaboration designed to address these challenges and de-risk the drug development process by jointly validating a set of CHR multimodal biomarkers and clinical profiles that reliably predict psychosis and non-psychosis outcomes.

Research Scope and Objectives

The AMP SCZ initiative has generated a set of drug development tools (biomarkers and clinical outcome measures, including the Positive Symptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS (PSYCHS)) to create algorithms that can reliably and validly distinguish the clinical course of individuals with CHR (conversion to psychosis, remission, and non-conversion/non-remission). As a follow-up to this initiative, this FOA will solicit applications for the CHR for Psychosis Clinical Trial Network, which will establish infrastructure to validate the utility of these tools in one or more PoP trials utilizing Phase 2 ready compound(s) that have been selected by the AMP SCZ Steering Committee. 

The ultimate goal of this FOA is to determine whether the biological and clinical outcome measures developed in the AMP SCZ observational study are intermediate readouts of drug response and/or connected to the proposed mechanisms underlying schizophrenia. The PoP trial will evaluate the potential of the selected compound(s) to detect a signal on one or more biological or clinical outcome measures within a 12-16 week time frame and generate novel insights into early intervention in CHR for psychosis.  

Potential applicants are strongly encouraged to consult with NIMH staff as early as possible when developing plans for an application. This early contact will provide an opportunity to clarify NIH policies and guidelines and help to identify whether the proposed project is consistent with NIMH program priorities and FOA goals.

Expected outcomes of the clinical trial(s) include:

• Assessment of the utility of clinical outcomes and biological measures developed in the AMP SCZ observational study
• Assessment of the ability to detect a change in signal using biological or clinical outcome measurement within a 12-16 week study time period
• Demonstrate functionality of an adaptive study design informed by data from the ongoing AMP SCZ observational study (https://www.ampscz.org/scientists/design)
• Identify primary and secondary hypotheses for what can be learned, including feasibility and utility of biomarkers for stratification and change, being mindful of burden and possible placebo response

Parameters of the clinical trial network are anticipated to include the following:

• There may be 10-15 clinical sites (depending on final sample size requirements; estimated 4 to 10 participants/site)
• Sites should have experience running clinical trials, a broad referral network, and high participant flow
• The network should have expertise in the range of outcome measures currently being examined in the AMP SCZ observational study, as described in the published protocol (https://www.ampscz.org/scientists/protocols)
• Sites should optimize costs and efficiency of the study
• There should be a minimum of 100 participants (minimum 30 participants per arm)
• Trials will evaluate 1-2 compounds selected by the AMP SCZ Steering Committee
• Study design is expected to employ a fixed dose approach (single dose versus placebo, or two doses if one compound is selected)
• Experience with investigator-filed Investigational New Drug (IND) applications and regulatory reporting
• To enable the rapid collection of data (considering efficiency, timeliness and cost), and to simplify regulatory processes, it is anticipated that the network will be restricted to U.S.-based sites under a central Institutional Review Board (IRB).

TBD

Public/State Controlled Institution of Higher Education
Private Institution of Higher Education
Nonprofit with 501(c)(3) IRS Status (Other than Institution of Higher Education)
Small Business
For-Profit Organization (Other than Small Business)
State Government
Indian/Native American Tribal Government (Federally Recognized)
County governments
Independent school districts
Public housing authorities/Indian housing authorities
Indian/Native American Tribally Designated Organization (Native American tribal organizations (other than Federally recognized tribal governments)
U.S. Territory or Possession
Indian/Native American Tribal Government (Other than Federally Recognized)
Regional Organization

Applications are not being solicited at this time. 

Please direct all inquiries to:

Jonathan Sabbagh, PhD
National Institute of Mental Health (NIMH)
Telephone: 301-594-2557
Email: jonathan.sabbagh@nih.gov