## Protocol Section
### Identification Module
**NCT ID:** NCT05948579

**Brief Title:** Department of Defense PTSD Adaptive Platform Trial - Intervention B - Vilazodone

**Official Title:** 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

#### Organization Study ID Info
**ID:** S-21-02 (Vilazodone)
#### Organization
**Class:** FED
**Full Name:** U.S. Army Medical Research and Development Command
### Status Module
#### Completion Date
**Date:** 2026-09

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-01-29

**Type:** ACTUAL

**Last Update Submit Date:** 2024-01-25

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-03

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-03

**Type:** ESTIMATED

**Status Verified Date:** 2024-01

#### Study First Post Date
**Date:** 2023-07-17
**Type:** ACTUAL
**Study First Submit Date:** 2023-07-05
**Study First Submit QC Date:** 2023-07-05
### Sponsor Collaborators Module

#### Collaborators

**Class:** INDUSTRY

**Name:** PPD

**Class:** OTHER

**Name:** Berry Consultants

**Class:** INDUSTRY

**Name:** Idorsia Pharmaceuticals Ltd.

**Class:** INDUSTRY

**Name:** Cambridge Cognition Ltd

**Class:** UNKNOWN

**Name:** Citeline

#### Lead Sponsor

**Class:** FED

**Name:** U.S. Army Medical Research and Development Command

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Oversight Has DMC:** True

### Description Module

**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.

Intervention B - Vilazodone will assess the safety and efficacy of vilzodone in participants with PTSD.

Please see NCT05422612 for information on the S-21-02 Master Protocol.

**Detailed Description:** The general structure of this Adaptive Platform Trial (APT) consists of a 30-day Screening Period, a 12-week Platform Treatment Period, and a 4-week Safety Follow-up. The S-21-02 Platform Trial will evaluate the safety and efficacy of multiple investigational products for the treatment of PTSD (see NCT05422612 for Master Protocol information). Participants are randomized among the multiple cohorts in the study and the resulting randomization enables sharing/pooling of control subjects, where all interventions may be compared to a common control (placebo). This record only includes information relevant to the vilazodone cohort.

Once a participant meets all eligibility criteria for the Master Protocol, eligibility for each currently enrolling intervention cohort is assessed. Eligible participants will be randomized with equal probability into a cohort. Participants randomized to the vilazodone cohort are then randomly assigned to receive either vilazodone or placebo in a ratio defined by the number of cohorts for which they are eligible, for the duration of the 12-week treatment period.

Parties interested in having their intervention considered for testing within the DOD PTSD APT should complete a request for information form using this webpage https://citeline.qualtrics.com/jfe/form/SV_0oDoJXvIL7EFM1M.

### Conditions Module

**Conditions:**

- Post Traumatic Stress Disorder

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

**Intervention Model Description:** Vilazodone is one of multiple interventions that will be tested in this adaptive platform trial (NCT05422612).

##### Masking Info

**Masking:** QUADRUPLE

**Masking Description:** 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).

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 200

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Intervention Names:**

- Drug: Intervention B Vilazodone Hydrochloride (HCl)

**Label:** Intervention B Vilazodone

**Type:** EXPERIMENTAL

#### Arm Group 2

**Intervention Names:**

- Drug: Intervention B Placebo

**Label:** Intervention B Placebo

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Intervention B Vilazodone

**Description:** 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.

**Name:** Intervention B Vilazodone Hydrochloride (HCl)

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Intervention B Placebo

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

**Name:** Intervention B Placebo

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** 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.

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

**Time Frame:** 12 Weeks

**Description:** 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).

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

**Time Frame:** 12 Weeks

#### Secondary Outcomes

**Description:** The TEAEs recorded during the study will be summarized by system organ class, preferred term, and treatment group. Adverse events and medical history will be coded using the most current version of MedDRA.

**Measure:** Frequency of treatment-emergent adverse events (TEAEs).

**Time Frame:** 12 Weeks

**Description:** The TEAEs recorded during the study will be summarized by system organ class, preferred term, and treatment group. Adverse events and medical history will be coded using the most current version of MedDRA.

**Measure:** Severity of treatment-emergent adverse events (TEAEs).

**Time Frame:** 12 Weeks

**Description:** The SAEs recorded during the study will be summarized by system organ class, preferred term, and treatment group. Adverse events and medical history will be coded using the most current version of MedDRA.

**Measure:** Frequency of serious adverse events (SAEs).

**Time Frame:** 12 Weeks

**Description:** The SAEs recorded during the study will be summarized by system organ class, preferred term, and treatment group. Adverse events and medical history will be coded using the most current version of MedDRA.

**Measure:** Severity of serious adverse events (SAEs).

**Time Frame:** 12 Weeks

**Description:** A relative 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.

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

**Time Frame:** 12 Weeks

**Description:** ≥30% reduction from Baseline to 12 Weeks in the Clinician-Administered PTSD Scale for DSM-5 Revised (CAPS-5-R), Past Month total score. The range of the scale is 0-200. The higher the score, the worse the PTSD severity. The larger the decrease in score from baseline, the better the outcome.

**Measure:** Number of participants with a Response Rate ≥30%

**Time Frame:** 12 Weeks

**Description:** ≥50% reduction from Baseline to 12 Weeks in the Clinician-Administered PTSD Scale for DSM-5 Revised (CAPS-5-R), Past Month total score. The range of the scale is 0-200. The higher the score, the worse the PTSD severity. The larger the decrease in score from baseline, the better the outcome.

**Measure:** Number of participants with a Response Rate ≥50%

**Time Frame:** 12 Weeks

**Description:** Achieving remission: defined as the Clinician-Administered PTSD Scale for DSM-5 Revised (CAPS-5-R), Past Month total score \<18. The range of the scale is 0-200. The higher the score, the worse the PTSD severity.

**Measure:** Number of participants Achieving Remission.

**Time Frame:** 12 Weeks

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

No additional inclusion criteria beyond the inclusion criteria specified in the Master Protocol (NCT05422612).

Exclusion Criteria:

The following exclusion criteria are in addition to the exclusion criteria specified in the Master Protocol (NCT05422612).

1. History of treatment for PTSD with vilazodone at doses of 20 to 40 mg daily, for at least 4 weeks.

**Gender Based:** True

**Gender Description:** 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:** True

**Maximum Age:** 65 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** kimberly.a.delcarmen.civ@health.mil

**Name:** Dr. Kimberly del Carmen

**Phone:** Please reach out by email

**Role:** CONTACT

### References Module

#### References

**Citation:** 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

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000068099

- Term: Trauma and Stressor Related Disorders

- ID: D000001523

- Term: Mental Disorders

### Condition Browse Module - Browse Branches

- Abbrev: BXM

- Name: Behaviors and Mental Disorders

- Abbrev: All

- Name: All Conditions

- Abbrev: BC26

- Name: Wounds and Injuries

### Condition Browse Module - Browse Leaves

- ID: M16103

- Name: Stress Disorders, Post-Traumatic

- Relevance: HIGH

- As Found: Post Traumatic Stress Disorder

- ID: M24916

- Name: Stress Disorders, Traumatic

- Relevance: HIGH

- As Found: Traumatic Stress Disorder

- ID: M17685

- Name: Wounds and Injuries

- Relevance: LOW

- As Found: Unknown

- ID: M222

- Name: Trauma and Stressor Related Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M4815

- Name: Mental Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M14473

- Name: Psychotic Disorders

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000040921

- Term: Stress Disorders, Traumatic

- ID: D000013313

- Term: Stress Disorders, Post-Traumatic

### Intervention Browse Module - Ancestors

- ID: D000000928

- Term: Antidepressive Agents

- ID: D000011619

- Term: Psychotropic Drugs

- ID: D000017367

- Term: Selective Serotonin Reuptake Inhibitors

- ID: D000014179

- Term: Neurotransmitter Uptake Inhibitors

- ID: D000049990

- Term: Membrane Transport Modulators

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000018377

- Term: Neurotransmitter Agents

- ID: D000018490

- Term: Serotonin Agents

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000058825

- Term: Serotonin 5-HT1 Receptor Agonists

- ID: D000017366

- Term: Serotonin Receptor Agonists

### Intervention Browse Module - Browse Branches

- Abbrev: PsychDr

- Name: Psychotropic Drugs

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M453

- Name: Vilazodone Hydrochloride

- Relevance: HIGH

- As Found: Moxifloxacin Ophthalmic

- ID: M4247

- Name: Antidepressive Agents

- Relevance: LOW

- As Found: Unknown

- ID: M14474

- Name: Psychotropic Drugs

- Relevance: LOW

- As Found: Unknown

- ID: M19649

- Name: Selective Serotonin Reuptake Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M15512

- Name: Serotonin

- Relevance: LOW

- As Found: Unknown

- ID: M20504

- Name: Neurotransmitter Agents

- Relevance: LOW

- As Found: Unknown

- ID: M29240

- Name: Serotonin 5-HT1 Receptor Agonists

- Relevance: LOW

- As Found: Unknown

- ID: M19648

- Name: Serotonin Receptor Agonists

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000069503

- Term: Vilazodone Hydrochloride

### Misc Info Module

- Version Holder: 2024-05-24
