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
Overview
- Phase
- Phase 2
- Intervention
- Intervention A Fluoxetine Hydrochloride (HCl)
- Conditions
- Post Traumatic Stress Disorder
- Sponsor
- Global Coalition for Adaptive Research
- Enrollment
- 800
- Locations
- 10
- Primary Endpoint
- Absolute change in the Clinician-Administered PTSD Scale-5-Revised (CAPS-5-R) Past Month total score at Week 12 (Final/Early termination Visit).
- Status
- Recruiting
- Last Updated
- 7 months ago
Overview
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 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •A participant must meet all the following criteria to be eligible to participate in this study:
- •Is willing and able to provide written informed consent.
- •≥18 and \<65 years of age at Screening.
- •Meets Diagnostic and Statistical Manual for Mental Disorders, 5th edition (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.
- •Is currently serving, or has previously served, in a branch of the US military service (ie, Air Force, Army, Navy, Marine Corps, and Coast Guard including Reserves and National Guard).
- •Agrees to consistently use an acceptable method of birth control as defined in Section 7.4.2 (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 treatment 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 Follicle-stimulating hormone (FSH) of \>40 U/mL, per central laboratory testing must be documented. Surgical sterility (hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) must be documented.
Exclusion Criteria
- •A participant who meets any of the following criteria will not be eligible to participate in this trial:
- •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 per Section 8.5.1 or cohort-specific restrictions (see cohort-specific appendices), is unable/unwilling to discontinue medications, or in the PI's judgement, cannot discontinue medications. Subjects 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.
- •In the 3 months prior to the Baseline visit, has initiated or terminated individual or group PTSD specific psychotherapy (eg, Eye Movement Desensitization \& Reprocessing, Prolonged Exposure, Cognitive Processing Therapy, Stress Inoculation Training, Present Centered Therapy), or therapy is anticipated to conclude during the study. Completion of ≤2 sessions in the prior 3 months with no plans to continue is not exclusionary. Participants in stable trauma-focused or non-trauma focused therapy must agree to continue treatment for the duration of participation in the study.
- •Has undergone or plans to undergo gender reassignment surgery. Note: participants who are currently undergoing stable hormone replacement therapy are eligible for inclusion in the study.
Arms & Interventions
Intervention A: Fluoxetine HCl
Intervention: Intervention A Fluoxetine Hydrochloride (HCl)
Intervention A Placebo
Intervention: Intervention A Placebo
Intervention B Vilazodone
Intervention: Intervention B Vilazodone Hydrochloride (HCl)
Intervention B Placebo
Intervention: Intervention B Placebo
Intervention C Daridorexant
Intervention: Intervention C Daridorexant
Intervention C Placebo
Intervention: Intervention C Placebo
Intervention D SLS-002
Intervention: Intervention D SLS-002
Intervention D Placebo
Intervention: Intervention D Placebo
Outcomes
Primary Outcomes
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
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.
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
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).
Secondary Outcomes
- 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)
- Number of participants with a Response Rate ≥30%(12 Weeks)
- Number of participants with a Response Rate ≥50%(12 Weeks)
- Number of participants Achieving Remission(12 Weeks)