Trial Outcomes & Findings for Safety and Immunogenicity Study of Recombinant Thrombin (rThrombin) in Pediatric Participants (NCT NCT00859547)

NCT ID: NCT00859547

Last Updated: 2012-01-26

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 30 participants
• Primary outcome timeframe: Days 1 through 29, continuously
• Results posted on: 2012-01-26

Participant Flow

Of the 32 participants who signed informed consent in this study, 30 were actually enrolled and received treatment with rThrombin.

Participant milestones

Measure	rThrombin, 1000 IU/mL Recombinant thrombin (rThrombin), 1000 IU/mL, applied topically during a single surgery procedure on Day 1.
Overall Study STARTED	30
Overall Study COMPLETED	28
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Measure	rThrombin, 1000 IU/mL Recombinant thrombin (rThrombin), 1000 IU/mL, applied topically during a single surgery procedure on Day 1.
Overall Study Lost to Follow-up	1
Overall Study Parent withdrew consent	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	rThrombin, 1000 IU/mL n=30 Participants Recombinant thrombin (rThrombin), 1000 IU/mL, applied topically during a single surgery procedure on Day 1.
Age, Customized 0-2 years	11 participants n=5 Participants
Age, Customized 3-6 years	8 participants n=5 Participants
Age, Customized 7-11 years	3 participants n=5 Participants
Age, Customized 12-17 years	8 participants n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants
Race/Ethnicity, Customized American Indian/Alaskan native	1 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	6 participants n=5 Participants
Race/Ethnicity, Customized Hispanic	9 participants n=5 Participants
Race/Ethnicity, Customized White	14 participants n=5 Participants

PRIMARY outcome

Timeframe: Days 1 through 29, continuously

Population: Participants who received treatment with rThrombin.

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

Outcome measures

Measure	rThrombin, 1000 IU/mL n=30 Participants Recombinant thrombin (rThrombin), 1000 IU/mL, applied topically during a single surgery procedure on Day 1.
Number of Participants With Death, Serious Adverse Events, Treatment-related Adverse Events (AE), AEs Leading to Discontinuation, and AEs of Hypersensitivity Deaths	0 Participants
Number of Participants With Death, Serious Adverse Events, Treatment-related Adverse Events (AE), AEs Leading to Discontinuation, and AEs of Hypersensitivity Serious adverse events	1 Participants
Number of Participants With Death, Serious Adverse Events, Treatment-related Adverse Events (AE), AEs Leading to Discontinuation, and AEs of Hypersensitivity Treatment-related adverse events (AEs)	0 Participants
Number of Participants With Death, Serious Adverse Events, Treatment-related Adverse Events (AE), AEs Leading to Discontinuation, and AEs of Hypersensitivity AEs leading to discontinuation	0 Participants
Number of Participants With Death, Serious Adverse Events, Treatment-related Adverse Events (AE), AEs Leading to Discontinuation, and AEs of Hypersensitivity AEs of hypersensitivity	3 Participants

PRIMARY outcome

Timeframe: Days 1 through 29, continuously

Population: Participants who received treatment with rThrombin.

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.

Outcome measures

Measure	rThrombin, 1000 IU/mL n=30 Participants Recombinant thrombin (rThrombin), 1000 IU/mL, applied topically during a single surgery procedure on Day 1.
Number of Participants With AEs by Maximum Severity Mild (0-2 years, n=11)	3 Participants
Number of Participants With AEs by Maximum Severity Mild (3-6 years, n=8)	3 Participants
Number of Participants With AEs by Maximum Severity Mild (7-11 years, n=3)	0 Participants
Number of Participants With AEs by Maximum Severity Mild (12-17 years, n=8)	3 Participants
Number of Participants With AEs by Maximum Severity Moderate (0-2 years, n=11)	1 Participants
Number of Participants With AEs by Maximum Severity Moderate (3-6 years, n=8)	5 Participants
Number of Participants With AEs by Maximum Severity Moderate (7-11 years, n=3)	3 Participants
Number of Participants With AEs by Maximum Severity Moderate (12-17 years, n=8)	3 Participants
Number of Participants With AEs by Maximum Severity Severe (0-2 years, n=11)	3 Participants
Number of Participants With AEs by Maximum Severity Severe (3-6 years, n=8)	0 Participants
Number of Participants With AEs by Maximum Severity Severe (7-11 years, n=3)	0 Participants
Number of Participants With AEs by Maximum Severity Severe (12-17 years, n=8)	1 Participants
Number of Participants With AEs by Maximum Severity Life-threatening (0-2 years, n=11)	3 Participants
Number of Participants With AEs by Maximum Severity Life-threatening (3-6 years, n=8)	0 Participants
Number of Participants With AEs by Maximum Severity Life-threatening (7-11 years, n=3)	0 Participants
Number of Participants With AEs by Maximum Severity Life-threatening (12-17 years, n=8)	0 Participants

PRIMARY outcome

Timeframe: Baseline and Day 29 from Baseline

Population: Participants who received treatment with rThrombin.

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

Outcome measures

Measure	rThrombin, 1000 IU/mL n=30 Participants Recombinant thrombin (rThrombin), 1000 IU/mL, applied topically during a single surgery procedure on Day 1.
Number of Participants With Clinical Laboratory Findings of Grade O or Higher in Platelet, White Blood Cell (WBC), Lymphocyte, and Neutrophil Counts Grade 0, low platelets (Day 29, N=25)	25 Participants
Number of Participants With Clinical Laboratory Findings of Grade O or Higher in Platelet, White Blood Cell (WBC), Lymphocyte, and Neutrophil Counts Grade 0, low WBC (Baseline)	30 Participants
Number of Participants With Clinical Laboratory Findings of Grade O or Higher in Platelet, White Blood Cell (WBC), Lymphocyte, and Neutrophil Counts Grade 0, low WBC (Day 29, N=26)	26 Participants
Number of Participants With Clinical Laboratory Findings of Grade O or Higher in Platelet, White Blood Cell (WBC), Lymphocyte, and Neutrophil Counts Grade 0, low platelets (Baseline)	30 Participants
Number of Participants With Clinical Laboratory Findings of Grade O or Higher in Platelet, White Blood Cell (WBC), Lymphocyte, and Neutrophil Counts Grade 0, low lymphocytes (Baseline, N=29)	28 Participants
Number of Participants With Clinical Laboratory Findings of Grade O or Higher in Platelet, White Blood Cell (WBC), Lymphocyte, and Neutrophil Counts Grade 0, low lymphocytes (Day 29, N=25)	25 Participants
Number of Participants With Clinical Laboratory Findings of Grade O or Higher in Platelet, White Blood Cell (WBC), Lymphocyte, and Neutrophil Counts Grade 1, low lymphocytes (Baseline, N=29)	1 Participants
Number of Participants With Clinical Laboratory Findings of Grade O or Higher in Platelet, White Blood Cell (WBC), Lymphocyte, and Neutrophil Counts Grade 1, low lymphocytes (Day 29, N=25)	0 Participants
Number of Participants With Clinical Laboratory Findings of Grade O or Higher in Platelet, White Blood Cell (WBC), Lymphocyte, and Neutrophil Counts Grade 0, neutrophils (Baseline, N=29)	29 Participants
Number of Participants With Clinical Laboratory Findings of Grade O or Higher in Platelet, White Blood Cell (WBC), Lymphocyte, and Neutrophil Counts Grade 0, neutrophils (Day 29, N=25)	24 Participants
Number of Participants With Clinical Laboratory Findings of Grade O or Higher in Platelet, White Blood Cell (WBC), Lymphocyte, and Neutrophil Counts Grade 2, low neutrophils (Baseline)	0 Participants
Number of Participants With Clinical Laboratory Findings of Grade O or Higher in Platelet, White Blood Cell (WBC), Lymphocyte, and Neutrophil Counts Grade 2, low neutrophils (Day 29, N=25)	1 Participants

PRIMARY outcome

Timeframe: Baseline and Day 29 from Baseline

Population: Participants who received treatment with rThrombin.

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.

Outcome measures

Measure	rThrombin, 1000 IU/mL n=30 Participants Recombinant thrombin (rThrombin), 1000 IU/mL, applied topically during a single surgery procedure on Day 1.
Number of Participants With Clinical Laboratory Findings of Grade 0 or Higher in Hemoglobin Levels Grade 1 low hemoglobin (Baseline)	13 Participants
Number of Participants With Clinical Laboratory Findings of Grade 0 or Higher in Hemoglobin Levels Grade 1 low hemoglobin (Day 29, N=26)	7 Participants
Number of Participants With Clinical Laboratory Findings of Grade 0 or Higher in Hemoglobin Levels Grade 2 low hemoglobin (Baseline)	4 Participants
Number of Participants With Clinical Laboratory Findings of Grade 0 or Higher in Hemoglobin Levels Grade 2 low hemoglobin (Day 29, N=26)	5 Participants
Number of Participants With Clinical Laboratory Findings of Grade 0 or Higher in Hemoglobin Levels Grade 3 low hemoglobin (Baseline)	1 Participants
Number of Participants With Clinical Laboratory Findings of Grade 0 or Higher in Hemoglobin Levels Grade 3 low hemoglobin (Day 29, N=26)	0 Participants
Number of Participants With Clinical Laboratory Findings of Grade 0 or Higher in Hemoglobin Levels Grade 4 low hemoglobin (Baseline)	0 Participants
Number of Participants With Clinical Laboratory Findings of Grade 0 or Higher in Hemoglobin Levels Grade 4 low hemoglobin (Day 29, N=26)	0 Participants

PRIMARY outcome

Timeframe: Baseline and Day 29 from Baseline

Population: Participants who received treatment with rThrombin.

ULN=upper level of normal. Grade 0=normal; Grade 1=>ULN to 1.5 x ULN.

Outcome measures

Measure	rThrombin, 1000 IU/mL n=30 Participants Recombinant thrombin (rThrombin), 1000 IU/mL, applied topically during a single surgery procedure on Day 1.
Number of Participants With Clinical Laboratory Findings of Grade 0 or Higher in Creatinine Levels Grade 0 high creatinine (Baseline, N=30)	30 Participants
Number of Participants With Clinical Laboratory Findings of Grade 0 or Higher in Creatinine Levels Grade 0 high creatinine (Day 29, N=26)	25 Participants
Number of Participants With Clinical Laboratory Findings of Grade 0 or Higher in Creatinine Levels Grade 1 high creatinine (Baseline)	0 Participants
Number of Participants With Clinical Laboratory Findings of Grade 0 or Higher in Creatinine Levels Grade 1 high creatinine (Day 29, N=26)	1 Participants

PRIMARY outcome

Timeframe: Baseline and Day 29 from Baseline

Population: Participants who received treatment with rThrombin.

ULN=upper limit of normal. Grade 0=normal; Grade 1=ULN to 1.5 x ULN.

Outcome measures

Measure	rThrombin, 1000 IU/mL n=29 Participants Recombinant thrombin (rThrombin), 1000 IU/mL, applied topically during a single surgery procedure on Day 1.
Number of Participants With Elevations in the Coagulation Parameter of Activated Partial Thromboplastin Time (aPPT)of Grade 0 or Higher Grade 0 high aPPT (Baseline, N=29)	22 Participants
Number of Participants With Elevations in the Coagulation Parameter of Activated Partial Thromboplastin Time (aPPT)of Grade 0 or Higher Grade 0 high aPPT (Day 29, N=24)	19 Participants
Number of Participants With Elevations in the Coagulation Parameter of Activated Partial Thromboplastin Time (aPPT)of Grade 0 or Higher Grade 1 high aPPT (Baseline, N=29)	7 Participants
Number of Participants With Elevations in the Coagulation Parameter of Activated Partial Thromboplastin Time (aPPT)of Grade 0 or Higher Grade 1 high aPPT (Day 29, N=24)	5 Participants

PRIMARY outcome

Timeframe: Baseline and Day 29 from Baseline

Population: Participants who received treatment with rThrombin.

Grade 0=normal.

Outcome measures

Measure	rThrombin, 1000 IU/mL n=28 Participants Recombinant thrombin (rThrombin), 1000 IU/mL, applied topically during a single surgery procedure on Day 1.
Number of Participants With a High International Normalized Ratio (INR) of Prothrombin Time of Grade 0 or Higher Grade 0 INR High (Baseline, N=28)	28 Participants
Number of Participants With a High International Normalized Ratio (INR) of Prothrombin Time of Grade 0 or Higher Grade 0 INR High (Day 29, N=24)	24 Participants

SECONDARY outcome

Timeframe: At Day 29

Population: Participants who received study drug and had both baseline and on-treatment anti-rThrombin product antibody assessments.

Antibody-positive was defined as seroconversion or ≥1.0 unit (≥10-fold) increase in titer compared with antibody titer at baseline.

Outcome measures

Measure	rThrombin, 1000 IU/mL n=27 Participants Recombinant thrombin (rThrombin), 1000 IU/mL, applied topically during a single surgery procedure on Day 1.
Number of Participants WIth Positive Findings for Anti-rThrombin Product Antibody	0 Participants

Adverse Events

TOTAL

Serious events: 1 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Measure	TOTAL n=30 participants at risk
Immune system disorders TRANSPLANT REJECTION	3.3% 1/30
Infections and infestations SKIN GRAFT INFECTION	3.3% 1/30

Other adverse events

Measure	TOTAL n=30 participants at risk
Blood and lymphatic system disorders ANAEMIA	30.0% 9/30
Gastrointestinal disorders CONSTIPATION	6.7% 2/30
Gastrointestinal disorders VOMITING	6.7% 2/30
General disorders OEDEMA PERIPHERAL	6.7% 2/30
General disorders PYREXIA	10.0% 3/30
Immune system disorders TRANSPLANT REJECTION	10.0% 3/30
Infections and infestations BACTERAEMIA	6.7% 2/30
Infections and infestations SKIN GRAFT INFECTION	6.7% 2/30
Injury, poisoning and procedural complications PROCEDURAL PAIN	50.0% 15/30
Injury, poisoning and procedural complications SEROMA	6.7% 2/30
Injury, poisoning and procedural complications SKIN GRAFT FAILURE	6.7% 2/30
Injury, poisoning and procedural complications WOUND SECRETION	6.7% 2/30
Skin and subcutaneous tissue disorders EXCESSIVE GRANULATION TISSUE	6.7% 2/30
Skin and subcutaneous tissue disorders PRURITUS	43.3% 13/30
Vascular disorders HAEMATOMA	6.7% 2/30

Additional Information

John Pribble, Vice President, Medical Affairs; Scot Maxon, Scientific Information

ZymoGenetics

Phone: (206) 428-2756; (206) 434-3365

Email: John.Pribble@bms.com; Scot.Maxon@bms.com

Results disclosure agreements

• Principal investigator is a sponsor employee ZymoGenetics (ZG) agreements vary by trial, but each states that presentation/publication (p/p) cannot disclose Confidential Information (CI), excluding trial results; p/p may not begin until the earlier of 18 months after study end, ZG/lead investigator publishes, or ZG notification that multicenter publication is not planned; ZG has specified time for draft review before submission/presentation and may delay or modify content, require CI removal, and delay p/p for patent application filing.
• Publication restrictions are in place

Restriction type: OTHER