NCT05422612

Department of Defense PTSD Adaptive Platform Trial - Master Protocol

A Phase 2, Multi-center, Multi-arm, Randomized, Placebo-controlled, Double-blind, Adaptive Platform Study to Evaluate the Safety, Tolerability, and Efficacy of Potential Pharmacotherapeutic Interventions in Active-Duty Service Members and Veterans With PTSD

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 800 (estimated)
• Sponsor: Global Coalition for Adaptive Research · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Accepted

Summary

This is a Phase 2 randomized, double-blinded, placebo-controlled study that will evaluate multiple potential pharmacotherapeutic interventions for PTSD utilizing an adaptive platform trial design. Participants are randomized among the multiple cohorts in the study and the resulting randomization enables sharing/pooling of control participants, where all interventions may be compared to a common control (placebo). This master protocol describes the default procedures and analyses for all cohorts; treatment-specific procedures will be described in the Master Protocol cohort-specific appendices. Individual cohorts may have additional eligibility requirements, safety and efficacy procedures, or endpoints, which will be described in corresponding intervention-specific clinicaltrials.gov records.

Detailed description

The general structure of the Military and Veterans PTSD Adaptive Platform Clinical Trial (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. At quarterly interim analyses, unblinded data will be reviewed by an independent, firewalled Independent Statistical Analysis Committee (ISAC) and a Data and Safety Monitoring Board (DSMB). At each interim analysis, 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 subject population enriched (eg, either only biomarker "positive" or only biomarker "negative" subjects 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 complete a request for information form using this webpage https://citeline.qualtrics.com/jfe/form/SV\_8eTQKw6TNug4z42.

Conditions

• Post Traumatic Stress Disorder

Interventions

Type	Name	Description
DRUG	Intervention A Fluoxetine Hydrochloride (HCl)	Fluoxetine will be administered at 10 to 60 mg daily. The initial dose for all participants will be 10 mg daily for 1 week, then increased to 20 mg daily for 2 weeks, then increased to 40 mg daily for 2 weeks, then increased to 60 mg daily for the remainder of the trial. One reduction in dose due to tolerability will be allowed. When a participant's dose is decreased due to tolerability, the dose will not be increased.
DRUG	Intervention A Placebo	A matching placebo will be administered at 10 to 60 mg daily in the same regimen as the intervention.
DRUG	Intervention B Vilazodone Hydrochloride (HCl)	Vilazodone HCl will be administered at 10 mg once daily for 7 days, followed by 20 mg for 7 days, followed by 40 mg for the remainder of the trial. There must be a minimum of 7 days between dosage increases. One reduction in dose due to tolerability will be allowed. After Week 8, dose reduction for tolerability is allowed, but dose increase is not allowed.
DRUG	Intervention B Placebo	A matching placebo will be administered at 10 to 40 mg daily in the same regimen as the intervention.
DRUG	Intervention C Daridorexant	Daridorexant will be administered 50 mg once daily.
DRUG	Intervention C Placebo	A matching placebo will be administered at 50 mg daily in the same regimen as the intervention.
DRUG	Intervention D SLS-002	• SLS-002 will be administered via intranasal administration (one spray per nostril, per device) at 78 mg two times per week for the first eight weeks and then once a week for the last four weeks.
DRUG	Intervention D Placebo	A matching placebo will be administered via intranasal administration (one spray per nostril, per device) two times per week for the first eight weeks and then once a week for the last four weeks.

Timeline

• Start date: 2023-11-02
• Primary completion: 2026-03-01
• Completion: 2026-09-01
• First posted: 2022-06-16
• Last updated: 2025-09-08

Locations

10 sites across 1 country: United States

Regulatory

• FDA-regulated drug study