Safety and Immunogenicity Study of Recombinant Thrombin (rThrombin) in Pediatric Participants

Study Overview
=================
Brief Summary
-----------------
The objective of this study is to assess the safety and immunogenicity of recombinant thrombin (rThrombin) administered as an aid to hemostasis during burn wound excision and skin grafting in pediatric patients, newborn through 17 years of age.

Detailed Description
-----------------
The safety, immunogenicity, and efficacy of rThrombin have been evaluated in 5 Phase 2 studies, 1 pivotal Phase 3 study, and 1 Phase 3b study, in surgical indications such as: spinal surgery, major hepatic resection, peripheral arterial bypass surgery, arteriovenous graft formation for hemodialysis access, and burn wound excision. Limited data currently exist on the effects of rThrombin exposure in pediatric patients. This Phase 4 trial aims to provide additional information on the use of rThrombin in children by evaluating the drug's safety and immunogenicity when administered as an aid to hemostasis during burn wound excision and skin grafting in pediatric burn patients.

Official Title
-----------------
A Phase 4, Open-Label, Single-Group Safety and Immunogenicity Study of RECOTHROM® (rThrombin) in Pediatric Subjects Undergoing Synchronous Burn Wound Excision and Skin Grafting

Conditions
-----------------
Blood Loss, Surgical

Intervention / Treatment
-----------------
* Biological: rThrombin, 1000 IU/mL


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age of newborn through 17 years at time of enrollment At least 1 skin graft recipient site measuring at least 1% of total body surface area (TBSA) Total initial burn wounds estimated to measure less than 40% of TBSA Bleeding indicating treatment with rThrombin during the surgical procedure Females of child-bearing potential must have a negative urine or serum pregnancy test within 2 days prior to study-drug treatment informed consent document signed by legal representative (guardian) and approved by an institutional review board/independent ethics committee (IRB/IEC) Participant has signed an IRB/IEC-approved pediatric assent document, if applicable Exclusion Criteria: Gestational age younger than 36 weeks at birth (for infants younger than 2 years) Documented active infection at the graft recipient site (participants with resolved infections at potential graft recipient sites are not excluded) Acute inhalation injury, as defined by bronchoscopic evidence of lower airway injury Currently undergoing autologous skin grafting for ischemic ulcer disease or cutaneous malignancies Presence of antibodies or hypersensitivity to the study drug or any of its components, other thrombin preparations, or coagulation factors Transfusion of whole blood, fresh frozen plasma, cryoprecipitate, or platelets within 24 hours prior to study-drug treatment (packed red blood cell transfusions are allowed) History of HIV infection or other immunodeficiency syndrome or is taking immunosuppressive or antirejection medications Medical, social, or psychosocial factors that, in the opinion of the investigator, could affect safety or compliance with study procedures Breastfeeding or being breastfed Treatment with any experimental agent within 30 days of study enrollment or treatment

Ages Eligible for Study
-----------------
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Recombinant thrombin (rThrombin), 1000 IU/mL<br> | Biological: rThrombin, 1000 IU/mL<br>* rThrombin,1000 IU/mL, 1000 IU/mL, applied topically to the bleeding site during a single surgery procedure on Day 1.<br>* Other names: RECOTHROM;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Death, Serious Adverse Events, Treatment-related Adverse Events (AE), AEs Leading to Discontinuation, and AEs of Hypersensitivity | An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=possibly, probably, or certainly related to and of unknown relationship to study treatment | Days 1 through 29, continuously | 
| Number of Participants With AEs by Maximum Severity | An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. Mild=asymptomatic or minor symptoms; intervention not indicated. Moderate=requiring only minimal, local, or noninvasive intervention. Severe=significant symptoms but not life-threatening; hospitalization or invasive intervention indicated. Life-threatening=indicating intensive care or urgent invasive intervention. | Days 1 through 29, continuously | 
| Number of Participants With Clinical Laboratory Findings of Grade O or Higher in Platelet, White Blood Cell (WBC), Lymphocyte, and Neutrophil Counts | Abnormal laboratory findings were recorded as AEs when considered clinically significant (unusual for the surgical population or individual participant) by the investigator, when associated with symptoms, when requiring specific treatment, or when requiring a change in participant management.LLN=lower level of normal. Platelets: Grade 0=normal. WBC: Grade 0=normal. Lymphocytes: Grade 0=normal; Grade 1=<LLN x 0.8-10^9/L. Neutrophils: Grade 0=normal; Grade 1=<LLN-1.5x10^9/L; Grade 2=<1.5-1.0x10^9/L | Baseline and Day 29 from Baseline | 
| Number of Participants With Clinical Laboratory Findings of Grade 0 or Higher in Hemoglobin Levels | LLN=lower level of normal. Grade 1=100 g/L to <LLN; Grade 2=80 to <100 g/L; Grade 3=65 to <80 g/L; Grade 4=<65 g/L. | Baseline and Day 29 from Baseline | 
| Number of Participants With Clinical Laboratory Findings of Grade 0 or Higher in Creatinine Levels | ULN=upper level of normal. Grade 0=normal; Grade 1=>ULN to 1.5 x ULN. | Baseline and Day 29 from Baseline | 
| Number of Participants With Elevations in the Coagulation Parameter of Activated Partial Thromboplastin Time (aPPT)of Grade 0 or Higher | ULN=upper limit of normal. Grade 0=normal; Grade 1=ULN to 1.5 x ULN. | Baseline and Day 29 from Baseline | 
| Number of Participants With a High International Normalized Ratio (INR) of Prothrombin Time of Grade 0 or Higher | Grade 0=normal. | Baseline and Day 29 from Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants WIth Positive Findings for Anti-rThrombin Product Antibody | Antibody-positive was defined as seroconversion or ≥1.0 unit (≥10-fold) increase in titer compared with antibody titer at baseline. | At Day 29 |