Safety and Tolerability of Intranasal Cenegermin Compared with Vehicle in Adults with Moderate to Severe Subacute Traumatic Brain Injury

The primary objective is to evaluate the safety and tolerability of intranasal cenegermin in adults with subacute traumatic brain injury. Secondary objectives include:

• Assessment of improvements in global outcome following intranasal administration compared to a vehicle.
• Evaluation of long-term safety and tolerability.
• Determination of systemic pharmacokinetics.
• Assessment of immunogenicity.

The study involves a total of 22 participants diagnosed with subacute moderate to severe traumatic brain injury. The population consists of male and female adults aged 18 to 70 years. Inclusion requires a clinical diagnosis based on a Glasgow Coma Scale score between 3 and 12, assessed within 24 hours of the injury. Participants must have undergone hospital evaluation within 2 to 8 weeks prior to providing informed consent. The diagnosis of traumatic brain injury must be confirmed via computed tomography. Additionally, subjects are expected to be discharged to a rehabilitation setting, either within a facility or at home.

This Phase 2a, randomized, double-blind, vehicle-controlled, parallel group, adaptive proof-of-concept study is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of intranasal cenegermin in adults with traumatic brain injury. The methodology involves administering either the test product or a placebo. The study begins with a screening visit to confirm eligibility based on clinical diagnosis and computed tomography findings. Participants are monitored for the incidence of treatment-emergent adverse events through 6 months following the initial administration. Secondary endpoints include assessments of outcomes using the Glasgow Outcome Scale – Extended, vital signs, electrocardiogram, clinical laboratory assessments, physical examinations, magnetic resonance imaging, and blood levels of anti-drug antibodies. Follow-up observations continue through 12 months post-administration. The trial involves monitoring for study discontinuation due to tolerability reasons.

The experimental medication, cenegermin, is a recombinant human nerve growth factor (rhNGF) provided as a nasal spray or powder for solution. This substance is administered via intranasal use to participants diagnosed with subacute moderate to severe traumatic brain injury (TBI).

The control group receives a vehicle used as a placebo.

Efficacy assessment in this study focuses on clinical outcomes in adult participants with subacute moderate to severe traumatic brain injury. The secondary endpoints include the incidence of sliding and good outcome as measured by the Glasgow Outcome Scale – Extended at month 6 following the initial administration of cenegermin.