Department of Defense PTSD Adaptive Platform Trial - Master Protocol

NCT05422612 | Suspended Phase 2 DMC FDA Drug

• 1 other identifier: S-21-02 / IND 157676
• Study Type: interventional
• Target: 800
• Locations: 1 country
• Sites: 9

Brief 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 available 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). The master protocol describes the default procedures and analyses for all cohorts; treatment-specific eligibility requirements, safety and efficacy procedures, or endpoints are described in the cohort-specific appendices and reflected in the intervention-specific clinicaltrials.gov records.

Conditions

Post Traumatic Stress Disorder

Outcome Measures

Primary Outcomes (2)

• Absolute change in the Clinician-Administered PTSD Scale-5-Revised (CAPS-5-R) Past Month total score at Week 12 (Final/Early termination Visit).

  A change in PTSD symptom severity from baseline as measured by CAPS-5-R Past Month. The range of the scale is 0-200. The higher the score at baseline, the worse the PTSD severity. The larger the decrease in score from baseline, the better the outcome.

  12 Weeks

• Incidence of new or worsening suicidal thoughts or behaviors as measured by change in Columbia Suicide Severity Rating Scale (C-SSRS) score from baseline.

  The C-SSRS is an assessment of suicidal ideation and behavior in clinical and research settings. The C-SSRS consists of 16 questions that ask about suicidal ideation and behaviors (the first 10 questions comprise the ideation subscale and the last 6 comprise the behavior subscale). This 5-item subscale ranges from a minimum of 0 (corresponding to no suicidal ideation) to a maximum of 5 (representing active suicidal ideation with plan and intent).

  12 Weeks

Secondary Outcomes (17)

• Frequency of treatment-emergent adverse events (TEAEs).

  12 Weeks

• Severity of treatment-emergent adverse events (TEAEs).

  12 Weeks

• Frequency of serious adverse events (SAEs)

  12 Weeks

• Severity of serious adverse events (SAEs).

  12 Weeks

• Relative change from Baseline to Week 12 in the Clinician-Administered PTSD Scale for DSM-5 Revised (CAPS-5-R), Past Month total score.

  12 Weeks

Study Arms (8)

Intervention A: Fluoxetine HCl

EXPERIMENTAL

Drug: Intervention A Fluoxetine Hydrochloride (HCl)

Intervention A Placebo

PLACEBO COMPARATOR

Drug: Intervention A Placebo

Intervention B Vilazodone HCl

EXPERIMENTAL

Drug: Intervention B Vilazodone Hydrochloride (HCl)

Intervention B Placebo

PLACEBO COMPARATOR

Drug: Intervention B Placebo

Intervention C Daridorexant

EXPERIMENTAL

Drug: Intervention C Daridorexant

Intervention C Placebo

PLACEBO COMPARATOR

Drug: Intervention C Placebo

Intervention D SLS-002

EXPERIMENTAL

Drug: Intervention D SLS-002

Intervention D Placebo

PLACEBO COMPARATOR

Drug: Intervention D Placebo

Interventions

Intervention A Placebo DRUG

A matching placebo will be administered at 10 to 60 mg daily in the same regimen as the intervention.

Intervention A Placebo

Intervention B Placebo DRUG

A matching placebo will be administered at 10 to 40 mg daily in the same regimen as the intervention.

Intervention B Placebo

Intervention C Daridorexant DRUG

Daridorexant will be administered 50 mg once daily.

Intervention C Daridorexant

Intervention C Placebo DRUG

A matching placebo will be administered at 50 mg daily in the same regimen as the intervention.

Intervention C Placebo

Intervention D SLS-002 DRUG

• 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.

Intervention D SLS-002

Intervention D Placebo DRUG

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.

Intervention D Placebo

Intervention A Fluoxetine Hydrochloride (HCl) DRUG

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.

Intervention A: Fluoxetine HCl

Intervention B Vilazodone Hydrochloride (HCl) DRUG

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.

Intervention B Vilazodone HCl

Eligibility Criteria

• Age: 18 Years - 65 Years
• Gender Eligibility Details: Participants who have undergone or plans to undergo gender reassignment surgery are not eligible. Participants who are currently undergoing stable hormone replacement therapy are eligible for inclusion in the study.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Is willing and able to provide written informed consent.
• ≥18 and \<65 years of age at Screening.
• Meets DSM-5 criteria for PTSD according to CAPS-5-R, Past Month assessment at Screening and Baseline.
• The index trauma must have occurred more than 3 months prior to Screening.
• Has a CAPS-5-R, Past Month total score of ≥26 at Screening and Baseline. Note: The CAPS-5 scoring grid will be used to score answers and to calculate the total score to determine eligibility.
• Participants must be able to read, speak, and understand English sufficiently to complete the CAPS-5, which is the primary efficacy endpoint and is administered by trained Centralized Assessors.
• Agrees to consistently use an acceptable method of birth control (required for both males and females who are of reproductive potential and sexually active with partners of the opposite sex) throughout the duration of participants' involvement in the study and for a minimum of 30 days after the last dose of study intervention or longer, as specified in the assigned cohort-specific appendices.
• For females of reproductive potential, acceptable birth control methods are defined as: hormonal contraceptives, intrauterine device, or double barrier contraception (ie, male condom and diaphragm, male condom or diaphragm with spermicidal gel or foam). Hormonal contraceptives must have been started at least 2 months prior to the Baseline Visit. In addition, agrees to no egg donation or harvesting for the duration of the study and for at least 30 days after the last dose of study intervention or as specified in the assigned cohort-specific appendices.
• Non-reproductive potential for females is defined by a post-menopausal (12 consecutive months without menses or surgically sterile). If in question, an FSH of \>40 U/mL, per central laboratory testing must be documented. Surgical sterility (hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) must be documented.
• Females of reproductive potential must have a negative pregnancy test at the Screening (serum) Visit and Baseline (urine) Visit.
• For males, adequate birth control methods will be defined as the use of double barrier contraception (e.g., male condom and diaphragm, male condom or diaphragm with spermicidal gel or foam). In addition, male participants must agree not to donate sperm for the duration of the study and for at least 30 days after the last dose of study intervention or as specified in the assigned cohort-specific appendices.
• Non-reproductive potential for males is defined as surgical sterility (i.e., vasectomy) at least 3 months prior to Baseline.
• Is able and willing to participate in study assessments and undergo blood draws.
• For participants who consent to the optional MRI: willingness to undergo MRI, e.g., is not claustrophobic, and has no contraindications to MRI.

You may not qualify if:

• Is pregnant or breastfeeding at the Screening or Baseline Visits or planning pregnancy during the study.
• Is at risk for suicide based on any of the following:
• Had any suicidal ideation or behavior (including preparatory behavior) that required psychiatric hospitalization in the 3 months prior to screening.
• Had more than 2 actual suicide attempts within the last 3 years, not including interrupted or aborted attempts, preparatory acts or behaviors, or non-suicidal self injurious behavior (as per C SSRS response).
• Has any history of suicidal ideation and/or intent following initiation of a medication used for psychiatric symptoms or disorders.
• Has any history of suicide-related hospitalization following initiation of a medication used for psychiatric symptoms or disorders.
• Is taking any prohibited medication or cohort-specific restrictions (see cohort-specific appendices), is unable/unwilling to discontinue medications, or in the PI's judgment, cannot discontinue medications. Participants must agree to a washout period of at least 14 days or 5 half-lives, whichever is longer, prior to the first dose of study intervention. Note, the half-life of the parent drug (not metabolites) should be used in this calculation.
• Meets DSM-5 (American Psychiatric Association 2013) criteria for moderate or severe AUD or other SUDs, including cannabis, hallucinogens, inhalants, opioids, sedatives, hypnotics, anxiolytics, or stimulants within 3 months of screening. Nicotine use disorder is allowed.
• Has a positive screen for illicit drugs (excluding cannabis) or positive alcohol screen (either positive on qualitative test or above .04% on a quantitative test) at the Baseline Visit.
• If the urine drug screen is positive at Screening (excluding cannabis), the participant will not immediately be excluded from participation in the study. The urine drug screen must be repeated at Baseline after at least 7 days since the initial test. If the urine drug screen is positive at Baseline (excluding cannabis), then the participant will be discontinued from the study.
• If the urine alcohol screen is positive at Screening, the participant will not immediately be excluded from participation in the study. If the urine alcohol screen is also positive at Baseline, then the participant will be discontinued from the study.
• Has a lifetime history or current symptoms of psychotic features, as determined by the MINI Psychotic Disorders and Mood Disorders with Psychotic Features screening questions.
• Has a history of neoplastic disease or completion of treatment in the last 5 years, except for treated basal cell or squamous cell carcinoma of the skin.
• Has any clinically significant abnormal findings on the 12-lead ECG at the Screening Visit or Baseline Visit, such as:
• Abnormal heart rhythm (such as atrial fibrillation, ventricular fibrillation, or torsade de pointes)

Sponsors & Collaborators

• U.S. Army Medical Research and Development Command: collaborator
• PPD Development, LP: collaborator
• Berry Consultants: collaborator
• Idorsia Pharmaceuticals Ltd.: collaborator
• Cambridge Cognition Ltd: collaborator
• Citeline: collaborator
• Global Coalition for Adaptive Research: lead

Study Sites (9)

Homestead Associates in Research, Inc.

Miami, Florida, 33032, United States

Location

Advanced Discovery Research

Atlanta, Georgia, 30318, United States

Location

Tripler Army Medical Center (TAMC)

Tripler AMC, Hawaii, 96859, United States

Location

Cincinnati Veteran's Affairs Medical Center

Fort Thomas, Kentucky, 41075, United States

Location

Walter Reed National Military Medical Center (WRNMC)

Bethesda, Maryland, 20889-5632, United States

Location

Upstate Clinical Research Associates, LLC

Williamsville, New York, 14221, United States

Location

Wilford Hall Ambulatory Surgical Center (WHASC)

San Antonio, Texas, 78236, United States

Location

Alexander T. Augusta Military Medical Center (ATAMMC):

Fort Belvoir, Virginia, 22060-5285, United States

Location

Madigan Army Medical Center

Joint Base Lewis McChord, Washington, 98433, United States

Location

Related Publications (1)

• Viele K. Allocation in platform trials to maintain comparability across time and eligibility. Stat Med. 2023 Jul 20;42(16):2811-2818. doi: 10.1002/sim.9750. Epub 2023 Apr 23.

  PMID: 37088912 BACKGROUND

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The overall 2-stage randomization scheme will be implemented by an unblinded statistician who is otherwise uninvolved in study operations. Participants will be assigned a study number at Screening (Subject ID). In the first stage of randomization, eligible participants who complete screening will be randomly assigned to an open platform cohort for which they are eligible (both site PIs and participants are aware of the cohort assignment) and, within that cohort, the second stage of randomization is to intervention vs placebo (double-blind) using Interactive Response Technology (IRT). For this APT, participant assignment to a cohort will not be blinded. The tablets/capsules used in the cohorts may not be visually similar between cohorts and blinding to cohort assignment is not necessary to avoid bias. However, within each cohort, participants, site personnel, contract research personnel and the sponsor will be blind to treatment assignment (intervention vs. placebo).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multiple interventions will be tested in this adaptive platform trial and each will be described in Master Protocol cohort-specific platform appendices.

Study Record Dates

• First Submitted: June 13, 2022
• First Posted: June 16, 2022
• Study Start: November 2, 2023
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2029
• Last Updated: June 30, 2026

Record last verified: 2026-06

Locations

US (9)