Phase 1 Study of HBN-1

Study Overview
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Brief Summary
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Phase 1 First-in Human randomized, open-label, active control standard of care study of the safety of HBN-1 administered as pharmacologically induced hypothermia as an adjunct to standard of care targeted temperature management in adult patients who have experienced out-of-hospital-cardiac arrest. HBN-1 will be administered IV as a loading dose infusion followed by a 12-hour maintenance infusion.

Detailed Description
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Phase 1 First-in Human randomized, open-label, active control standard of care study of the safety of HBN-1 administered as pharmacologically induced hypothermia as an adjunct to standard of care targeted temperature management in adult patients who have experienced out-of-hospital-cardiac arrest. HBN-1 will be administered as an IV solution according to a weight-based escalating loading dose infusion rate scheme involving three sequential cohorts with a loading dose of HBN 1 administered over 60 minutes (Cohort A), 45 minutes (Cohort B), or 30 minutes (Cohort C). For all cohorts, the loading dose will be followed by a 12-hour maintenance infusion of HBN-1. Dosing cohorts will include a minimum of 6 subjects randomized in a 2:1 ratio of HBN-1 plus standard of care versus standard of care alone. Individual cohorts may be expanded to up to a maximum of 12 subjects . If the cohort is expanded, the additional subjects will receive HBN-1 + SOC. During the loading dose and maintenance infusion, physical exam, temperature, assessment of shivering, ECG, vital signs, clinical laboratory, blood alcohol level, and neurologic status will be monitored.

Official Title
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A Phase 1 First-In-Human Study of HBN-1 in Patients Resuscitated Following Out-of-Hospital Cardiac Arrest

Conditions
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Cardiac Arrest

Intervention / Treatment
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* Drug: HBN-1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 40 to 80 years, inclusive Documented diagnosis of OHCA with ventricular tachycardia/fibrillation, asystole or pulseless electrical activity Return of spontaneous circulation within 50 minutes of the event FOUR Motor Score <4 Maximum estimated weight not to exceed 100 kg Exclusion Criteria: Return of spontaneous circulation >8 hours Known history of prior cardiac arrest, alcohol, or substance abuse or dependence Presumed etiology of cardiac arrest is trauma, hemorrhage, or sepsis Comfort measures only or anticipated withdrawal of life-support within 24 hours Is within a protected population group (eg, pregnant or breastfeeding or incarcerated persons) Has history or evidence of significant hepatic dysfunction (Sequential Organ Failure Assessment Hepatic score >2) Any other condition, that in the opinion of the investigator, would preclude the subject from being a suitable candidate, e.g. end-stage chronic illness with no reasonable expectation of survival to hospital discharge Is able to obey to verbal commands Is receiving IV vasopressin or lidocaine hydrochloride

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, open-label
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HBN-1 Plus Standard of Care<br>Subjects will receive an intravenous loading dose of HBN-1 followed by a 12 hour maintenance infusion plus standard of care targeted temperature management | Drug: HBN-1<br>* Intravenous infusion<br>|
| No Intervention: Standard of Care<br>Subjects will receive standard of care targeted temperature management only | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterize the safety and recommended Phase 2 loading dose infusion rate of HBN-1 | Safety and tolerability based on evaluation of adverse events, serious adverse events, physical examinations, vital signs measurements, electrocardiograms, and changes in clinical laboratory values (hematology, biochemistry, and urinalysis) | Initiation of TTM until a minimum of 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the incidence of the need for implementation of treatment to offset shivering | Number and proportion of subjects who require intervention for shivering. | Initiation of TTM until a minimum of 72 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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therapeutic temperature management; therapeutic hypothermia