Department of Defense PTSD Adaptive Platform Trial - Master Protocol

The general structure of the M-PACT consists of a 30-day Screening Period, a 12-week Treatment Period, and a 4-week Safety Follow-up. The trial will include up to 5 open cohorts (it is possible for 1 of the cohorts to begin sooner than the others, as necessary). Importantly, the integration of multi-modal biomarker assessments within the M-PACT allows for defining future cohorts based on to be determined biomarker signatures in a multi stage approach. Initial testing in non biomarker defined cohorts will be referred to as "main stage" testing, while testing in biomarker-defined cohorts will occur within "biomarker extensions." Initially designed as up to 5-arms versus control, the adaptive platform trial will continue enrollment until decisions are made to stop all cohorts. Interim analyses will be conducted at approximately quarterly intervals, beginning after at least 40 participants have been randomized and at least 10 participants have completed the End of Study (EOS) visit. At each interim analyses, unblinded data will be reviewed by an independent, firewalled ISAC and a DSMB. The possible cohort-level decisions that could be made by the prespecified adaptive plan include stopping enrollment to a cohort for futility, stopping enrollment to a cohort for anticipated success, or stopping enrollment to a cohort for reaching the maximum sample size. For cohort-specific interventions intending to pursue a labeling claim (which will be clearly stated in the cohort-specific appendix before cohort initiation), early stopping for success will not be considered. New cohorts for investigation can be added at any time. The DSMB may recommend stopping any cohort for safety reasons. Candidate biomarker data will be retrospectively analyzed after each cohort has completed main stage testing, and cohort testing may be re-initiated for prospective evaluation of the treatment in a participant population enriched (e.g., either only biomarker "positive" or only biomarker "negative" participants would be enrolled) or stratified based on biomarker status. In addition, candidate biomarkers (which may also be characterized or validated externally to the M-PACT) may be used to stratify randomization across cohorts or as a prospective enrichment strategy at the initiation of a cohort. Exploratory biomarker data will be evaluated throughout the trial to identify additional candidate biomarkers for testing within the M-PACT. For information specific to each intervention included in this platform trial, please refer to the below corresponding, separate, clinicaltrials.gov records: Vilazodone NCT05948579; Fluoxetine NCT05948553; Daridorexant NCT05948540; SLS-002 NCT06816433. Parties interested in having their intervention considered for testing within the M-PACT should email partners@gcaresearch.org