Clinical trial NCT06816433: Department of Defense PTSD Adaptive Platform Trial - Intervention D - SLS-002
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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Post Traumatic Stress Disorder
Lead sponsor: Global Coalition for Adaptive Research
Sponsor class: OTHER
Collaborators: name: U.S. Army Medical Research and Development Command
name: PPD Development, LP
name: Berry Consultants
name: Idorsia Pharmaceuticals Ltd.
name: Cambridge Cognition Ltd
name: Citeline
First posted: 2025-02-10
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: SLS-002 is one of multiple interventions that will be tested in this adaptive platform trial (NCT05422612).
Primary purpose: TREATMENT

Brief summary: This is a Phase 2 randomized, double-blinded, placebo-controlled study that will evaluate multiple potential pharmacotherapeutic interventions for Post Traumatic Stress Disorder (PTSD) utilizing an adaptive platform trial (APT) design.

Intervention D - SLS-002 will assess the safety and efficacy of SLS-002 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 SLS-002 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 SLS-002 cohort are then randomly assigned to receive either SLS-002 or placebo (in a ratio of 5:3; intervention:placebo), for the duration of the 12-week treatment period.

Parties interested in having their intervention considered for testing within the Military and Veterans PTSD Adaptive Platform Clinical Trial (M-PACT) should complete a request for information form using this webpage https://citeline.qualtrics.com/jfe/form/SV_8eTQKw6TNug4z42.

Eligibility criteria: Inclusion Criteria:

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

1. Is able to complete intranasal administration of study intervention.
2. Is able to refrain from alcohol or cannabis consumption/use on dosing days.
3. Is willing and able to attend dosing visits as outlined in the protocol (twice a week for the first 8 week and then once a week for Weeks 9 through 12) and agrees not to drive a car or operate machinery for 24 hours after receiving the study intervention.

Exclusion Criteria:

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

1. Has a history of seizures (other than childhood febrile seizures).
2. Has a body mass index \>40 or \<18 kg/m2 at Screening.
3. Has known, uncontrolled hypertension or blood pressure that, in the investigator's judgment, should exclude the subject at Screening or Baseline (blood pressure may be repeated as per the site's standard operating procedures).
4. Has a known history or current finding of cardiovascular disease, cerebrovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, congenital heart disease, ischemic heart disease, cardiac insufficiency, supraventricular, ventricular heart rhythm disorder, prolonged QT syndrome (ie, QTcF \>450 msec for males and \>470 msec for females) or associated risk factors (ie, hypokalemia, family history of long QT syndrome), syncope, cardiac conduction problems (eg, clinically significant heart block), exercise-related cardiac events including syncope and pre-syncope, clinically significant bradycardia, or other serious cardiac problems.
5. Has a concurrent chronic or acute illness, or other condition (eg, narcolepsy, uncontrolled hyper- or hypothyroidism) that might confound the results of safety assessments conducted in the study.
6. Has any medical condition that could interfere with the absorption of intranasal ketamine (eg, nasal polyps, clinically significant deviated septum \[corrected or persistent\], or other physical abnormalities of the nose).
7. Has a history of interstitial or ulcerative cystitis, overactive bladder, painful bladder
8. syndrome, chronic pelvic pain, frequent recurrent urinary tract infections, autoimmune disease, active urinary tract infection, history of prostate cancer, bladder cancer or bladder

   a. surgery, or symptoms suggestive of these disorders (eg, high urinary frequency, persistent urge to urinate).
9. Has any history of using ketamine or esketamine. Note previous use of ketamine for anesthesia is allowed.
10. Has known or suspected intolerance or hypersensitivity to the study intervention(s), closely related compounds, or any ingredients.
11. Does not meet or is not willing to comply with the requirements listed in protocol related to prohibited and restricted medications and therapies, as well as required washout periods prior to participation. Prohibited medications and therapies include, but are not limited to, monoamine oxidase inhibitors (MAOIs), chronic/frequent use of opioids or drugs with activity at the opioid receptor, psychostimulants, mood stabilizers/anticonvulsants, antipsychotics, or any medication/therapy that might confound the results of safety assessments conducted in the study. Subjects who have received any of these prohibited medications within 30 days of Screening are excluded from the study. Potent CYP 3A4 inhibitors, including nefazodone and fluvoxamine, are not permitted within 1 week of first dose and until at least 1 day after the last dose. Potent CYP 3A4 inducers, including a. St. John's wort, are not permitted within 30 days of first dose and until at least 1 day after the last dose.

Primary outcomes:
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).
timeFrame: 12 Weeks
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.
timeFrame: 12 Weeks
Secondary outcomes:
measure: Frequency of treatment-emergent adverse events (TEAEs).
timeFrame: 12 Weeks
measure: Severity of treatment-emergent adverse events (TEAEs).
timeFrame: 12 Weeks
measure: Frequency of serious adverse events (SAEs)
timeFrame: 12 Weeks
measure: Severity of serious adverse events (SAEs).
timeFrame: 12 Weeks
measure: Relative change from Baseline to Week 12 in CAPS-5-R, Past Month total score.
timeFrame: 12 Weeks
measure: Number of participants with a Response Rate ≥30%
timeFrame: 12 Weeks
measure: Number of participants with a Response Rate ≥50%
timeFrame: 12 Weeks
measure: Number of participants Achieving Remission.
timeFrame: 12 Weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix VA Healthcare System
state: Arizona
city: Miami
country: United States
facility: Homestead Associates in Research, Inc.
state: Florida
city: Atlanta
country: United States
facility: Advanced Discovery Research
state: Georgia
city: Fort Thomas
country: United States
facility: Cincinnati Veteran's Affairs Medical Center
state: Kentucky
city: Williamsville
country: United States
facility: Upstate Clinical Research Associates, LLC
state: New York
city: San Antonio
country: United States
facility: Wilford Hall Ambulatory Surgical Center (WHASC)
state: Texas
city: Joint Base Lewis McChord
country: United States
facility: Madigan Army Medical Center
state: Washington
Study officials:
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.