TBI Adaptive Platform Drug Trial

The primary objective of the TBI Adaptive Platform Drug Trial (APT) is to confirm safety, determine futility and identify whether any of the active treatment interventions improves the functional outcome in participants with TBI as defined by a Glasgow Coma Scale (GCS) between 9 and 15 and a positive head computerized tomography (CT+) scan identifying acute traumatic brain injury.

The APT will enroll approximately 672 participants assuming 25% attrition rate to achieve 6 month follow-up for 504 participants with Glasgow Coma Scale (GCS) between 9 and 15 and a positive head computerized tomography (CT+).  Participants must be enrolled and treated with first dose of investigational product within 12 hours of injury. Enrollment is anticipated to begin in the fall of 2023.

Multi-center, double-blind, placebo-controlled adaptive platform, precision medicine, trial conducted under a single multi-arm, multi-stage (MAMS) study with parallel groups. Participants will be randomized to receive one of four possible treatment interventions: Atorvastatin calcium, Minocycline hydrochloride, Candesartan cilexetil, and matching placebo.

The Outcomes Assessment Core will be utilized by collecting the Glasgow Outcome Scale-Extended (GOSE), using the “TBI-only” version (GOSE-TBI) that assesses functional impairment due only to the TBI, from Week 2 to Month 3 postinjury.  GOSE-TBI is the primary endpoint. Secondary endpoints collected will be the Brief Test of Adult Cognition by Telephone (BTACT) Composite z-score from Day 3 to Week 4 postinjury and the Rivermead Post Concussion Symptoms Questionnaire (RPQ) total score from Day 3 to Week 4.

The Biospecimen Biomarker Core will be collecting and analyzing neurofilament light chain (NfL), Ubiquitin C-terminal hydrolase L1 (UCH-L1), and glial fibrillary acidic protein (GFAP) levels at Week 2 postinjury in participants with TBI as compared to placebo.

The Imaging Core will oversee collection of imaging biomarkers at 2 weeks and 3 and 6 months postinjury for the measurement of structural features, diffusion parameters, and resting state functional MRI, and white matter structural and gray matter functional connectomics to define novel structural and functional endpoints.

The TBI Adaptive Platform Drug Trial is funded by the U.S. Army Medical Materiel Development Activity (USAMMDA) under the Medical Technology Enterprise Consortium Other Transactions Agreement Number W81XWH-15-9-0001.

More information can be found at clinicaltrials.gov.