Immunogenicity and Safety Study of rThrombin in Surgical Hemostasis

Study Overview
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Brief Summary
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The objective of this study is to assess the immunogenicity and safety of recombinant Thrombin (rThrombin) in patients with prior rThrombin exposure.

Detailed Description
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The safety, immunogenicity, and efficacy of rThrombin have been evaluated in Phase 2 and Phase 3 studies in the following surgical indications: spinal surgery, major hepatic resection, peripheral arterial bypass (PAB) surgery, arteriovenous (AV) graft formation for hemodialysis access, and skin graft surgery following burn injury. Limited data on rThrombin reexposure currently exist. This study will assess the immunogenicity and safety of rThrombin in participants who are undergoing a surgical procedure during which topical rThrombin application is planned and who previously received rThrombin in Phase 3 clinical trials or during prior spine, AV graft formation, or PAB surgical procedures.

Official Title
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A Phase 4, Open-Label, Single-Group Immunogenicity and Safety Study of Re-exposure to RECOTHROM� (rThrombin) in Surgical Hemostasis

Conditions
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Blood Loss, Surgical

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previous enrollment in a ZymoGenetics-sponsored Phase 3 study and the recipient of treatment with rThrombin in that study or the recipient of commercially-available rThrombin in a prior spine, arteriovenous graft formation, or peripheral artery bypass surgical procedure Age of 18 years or older at time of consent Bleeding indicating treatment with rThrombin during the course of the surgical procedure Signed informed consent document approved by an institutional review board or independent ethics committee Exclusion Criteria: Currently undergoing a procedure requiring cardiopulmonary bypass or involving the aortic arch Known hypersensitivity to rThrombin product or any of its components Currently undergoing a surgical procedure where the use of other thrombin-containing hemostatic agents is planned Medical, social, or psychosocial factors that, in the opinion of the investigator, could affect the participant's safety or compliance with study procedures Treatment with any experimental agent within 30 days of study enrollment or treatment

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rThrombin, 1000 IU/mL<br> | Biological: rThrombin, 1000 IU/mL<br>* At least 1 application of reconstituted rThrombin, 1000 IU/mL, applied topically directly to the bleeding site, per product labeling.<br>* Other names: RECOTHROM;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number or Participants With Antirecombinant Thrombin (rThrombin) Product Antibody at Baseline and Day 29 | Immunogenicity of rThrombin product was evaluated using an enzyme-linked immunosorbent assay for detection of antirThrombin product antibody and a neutralizing antibody assay to characterize the potential of antibodies to rThrombin product to neutralize the activity of human plasma-derived thrombin. | At baseline and Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, Adverse Events (AEs), Treatment-related Adverse Events, and AEs Leading to Discontinuation | 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. 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. Treatment-related=possibly, probably, or certainly related to and of unknown relationship to study treatment. | Baseline through Day 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. AE severity was assessed using Common Terminology Criteria for Adverse Events, Version 13.0: Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening; Grade 5=fatal. | Baseline to Day 29, continuously |