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Trial record 1 of 2 for:    LFB USA
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LR769 in Congenital Hemophilia Patients With Inhibitors Undergoing Elective Surgery or Invasive Procedures (PerSept3)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02548143
Recruitment Status : Completed
First Posted : September 14, 2015
Results First Posted : September 6, 2019
Last Update Posted : May 14, 2020
Sponsor:
Collaborator:
Laboratoire français de Fractionnement et de Biotechnologies
Information provided by (Responsible Party):
LFB USA, Inc.

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hemophilia
Intervention Biological: Coagulation Factor VIIa (Recombinant)
Enrollment 12
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Major Surgery (LR769 Initial Dose 200 μg/kg; Then 75 μg/kg) Minor Surgery (LR769 Initial Dose 75 μg/kg; Then 75 μg/kg)
Hide Arm/Group Description

Major surgical procedures were those that usually required ≥5 days of factor replacement in hemophilia patients with inhibitors and typically involved entry into a body cavity and/or organ removal or similarly complex procedures.

A dose of 200 μg/kg of LR769 administered within ≤2 minutes of the onset of the procedure was used as the initial dose before the surgical incision or start of the invasive procedure. The initial dose was followed by repeated administration of 75 μg/kg of LR769 every 2 hours (±5 minutes) for the first 48 hours after completion of the procedure. After 48 hours, dosing continued at 75 μg/kg of LR769 (not more frequently than every 2 hours) as follows:

Days 3-4: Intervals up to every 4 hours; Days 5-6: intervals up to every 6 hours; Days 7-10: Intervals up to every 8 hours; Days 11 to last administration of LR769: Intervals up to every 12 hours.

Minor surgical or other invasive procedures were those that usually required <5 days of factor replacement and usually involved the skin, mucous membranes, or superficial connective tissue. The minimum duration of LR769 infusion for minor procedures was 2 days. For less invasive procedures, the patient may have been treated for ≤48 hours if the investigator/designee determined a shorter duration was sufficient to achieve hemostasis.

A dose of 75 μg/kg of LR769 administered within ≤2 minutes of the onset of the procedure was used as the initial dose before the surgical incision or start of the invasive procedure. The initial dose was followed by repeated administration of 75 μg/kg of LR769 every 2 hours (±5 minutes) for the first 48 hours. From Day 3, dosing could continue at 75 μg/kg of LR769 at intervals of up to every 24 hours, but not more frequently than every 2 hours.

Period Title: Overall Study
Started 6 6
Completed 5 5
Not Completed 1 1
Reason Not Completed
Adverse Event             1             0
Withdrawal by Subject             0             1
Arm/Group Title Major Surgery (LR769 Initial Dose 200 μg/kg; Then 75 μg/kg) Minor Surgery (LR769 Initial Dose 75 μg/kg; Then 75 μg/kg) Total
Hide Arm/Group Description

Major surgical procedures were those that usually required ≥5 days of factor replacement in hemophilia patients with inhibitors and typically involved entry into a body cavity and/or organ removal or similarly complex procedures.

A dose of 200 μg/kg of LR769 administered within ≤2 minutes of the onset of the procedure was used as the initial dose before the surgical incision or start of the invasive procedure. The initial dose was followed by repeated administration of 75 μg/kg of LR769 every 2 hours (±5 minutes) for the first 48 hours after completion of the procedure. After 48 hours, dosing continued at 75 μg/kg of LR769 (not more frequently than every 2 hours) as follows:

Days 3-4: Intervals up to every 4 hours; Days 5-6: intervals up to every 6 hours; Days 7-10: Intervals up to every 8 hours; Days 11 to last administration of LR769: Intervals up to every 12 hours.

Minor surgical or other invasive procedures were those that usually required <5 days of factor replacement and usually involved the skin, mucous membranes, or superficial connective tissue. The minimum duration of LR769 infusion for minor procedures was 2 days. For less invasive procedures, the patient may have been treated for ≤48 hours if the investigator/designee determined a shorter duration was sufficient to achieve hemostasis.

A dose of 75 μg/kg of LR769 administered within ≤2 minutes of the onset of the procedure was used as the initial dose before the surgical incision or start of the invasive procedure. The initial dose was followed by repeated administration of 75 μg/kg of LR769 every 2 hours (±5 minutes) for the first 48 hours. From Day 3, dosing could continue at 75 μg/kg of LR769 at intervals of up to every 24 hours, but not more frequently than every 2 hours.

Total of all reporting groups
Overall Number of Baseline Participants 6 6 12
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 12 participants
<=18 years
2
  33.3%
4
  66.7%
6
  50.0%
Between 18 and 65 years
4
  66.7%
2
  33.3%
6
  50.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6 participants 6 participants 12 participants
34.0  (20.19) 16.0  (15.52) 25.0  (19.57)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 12 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
6
 100.0%
6
 100.0%
12
 100.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 12 participants
Hispanic or Latino
1
  16.7%
0
   0.0%
1
   8.3%
Not Hispanic or Latino
5
  83.3%
6
 100.0%
11
  91.7%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 12 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
  16.7%
3
  50.0%
4
  33.3%
White
5
  83.3%
3
  50.0%
8
  66.7%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 12 participants
Ukraine 3 3 6
South Africa 1 3 4
Mexico 1 0 1
Russia 1 0 1
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 6 participants 6 participants 12 participants
54.17  (25.974) 36.72  (21.506) 45.44  (24.494)
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 6 participants 6 participants 12 participants
156.3  (22.50) 137.8  (34.02) 147.1  (29.13)
BMI  
Mean (Standard Deviation)
Unit of measure:  Kg/ m^2
Number Analyzed 6 participants 6 participants 12 participants
20.88  (6.203) 17.61  (2.823) 19.24  (4.902)
1.Primary Outcome
Title Percentage of Surgical or Other Invasive Procedures Defined as "Good" or "Excellent" Response to LR769 Treatment as Assessed by the Investigator, Based on the Totality of the Assessments Performed on the Patient
Hide Description The final assessment was performed by the investigator at the study center 48 hours after the last dose of LR769 and was based upon the totality of the assessments performed on the patient at each time point. Excellent: postoperative blood loss similar to or less than expected following this type of procedure in a patient who does not have a bleeding disorder and who is undergoing the same surgical or other invasive procedure; no blood component transfusion is required. Good: postoperative blood loss greater, but not substantially greater than expected, following this type of procedure in a patient who does not have a bleeding disorder and who is undergoing the same surgical or other invasive procedure, not explained by a surgical/medical issue other than hemophilia; no unexpected need for blood component transfusion.
Time Frame 48 (±4) hours after the last administration of LR769
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population: All patients who received LR769 treatment, underwent a surgical or invasive procedure, and had at least one efficacy assessment.
Arm/Group Title Major Surgery (LR769 Initial Dose 200 μg/kg; Then 75 μg/kg) Minor Surgery (LR769 Initial Dose 75 μg/kg; Then 75 μg/kg)
Hide Arm/Group Description:

Major surgical procedures were those that usually required ≥5 days of factor replacement in hemophilia patients with inhibitors and typically involved entry into a body cavity and/or organ removal or similarly complex procedures.

A dose of 200 μg/kg of LR769 administered within ≤2 minutes of the onset of the procedure was used as the initial dose before the surgical incision or start of the invasive procedure. The initial dose was followed by repeated administration of 75 μg/kg of LR769 every 2 hours (±5 minutes) for the first 48 hours after completion of the procedure. After 48 hours, dosing continued at 75 μg/kg of LR769 (not more frequently than every 2 hours) as follows:

Days 3-4: Intervals up to every 4 hours; Days 5-6: intervals up to every 6 hours; Days 7-10: Intervals up to every 8 hours; Days 11 to last administration of LR769: Intervals up to every 12 hours.

Minor surgical or other invasive procedures were those that usually required <5 days of factor replacement and usually involved the skin, mucous membranes, or superficial connective tissue. The minimum duration of LR769 infusion for minor procedures was 2 days. For less invasive procedures, the patient may have been treated for ≤48 hours if the investigator/designee determined a shorter duration was sufficient to achieve hemostasis.

A dose of 75 μg/kg of LR769 administered within ≤2 minutes of the onset of the procedure was used as the initial dose before the surgical incision or start of the invasive procedure. The initial dose was followed by repeated administration of 75 μg/kg of LR769 every 2 hours (±5 minutes) for the first 48 hours. From Day 3, dosing could continue at 75 μg/kg of LR769 at intervals of up to every 24 hours, but not more frequently than every 2 hours.

Overall Number of Participants Analyzed 6 5
Overall Number of Units Analyzed
Type of Units Analyzed: Surgeries
6 5
Count of Units
Unit of Measure: Surgeries
Successes
4
  66.7%
5
 100.0%
Failures
2
  33.3%
0
   0.0%
2.Secondary Outcome
Title Percentages of Success as Defined as the Combination of "Good" and "Excellent" Responses by the Investigator or Designee
Hide Description Good: postoperative blood loss greater than expected following this type of procedure in a patient who does not have a bleeding disorder and who is undergoing the same surgical or other invasive procedure, not explained by a surgical/medical issue other than hemophilia; no unexpected need for blood component transfusion Excellent: postoperative blood loss similar to or less than expected following this type of procedure in a patient who does not have a bleeding disorder and who is undergoing the same surgical or other invasive procedure; no blood component transfusion is required
Time Frame 24 hours after procedure completion
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population: All patients who received LR769 treatment, underwent a surgical or invasive procedure, and had at least one efficacy assessment.
Arm/Group Title Major Surgery (LR769 Initial Dose 200 μg/kg; Then 75 μg/kg) Minor Surgery (LR769 Initial Dose 75 μg/kg; Then 75 μg/kg)
Hide Arm/Group Description:

Major surgical procedures were those that usually required ≥5 days of factor replacement in hemophilia patients with inhibitors and typically involved entry into a body cavity and/or organ removal or similarly complex procedures.

A dose of 200 μg/kg of LR769 administered within ≤2 minutes of the onset of the procedure was used as the initial dose before the surgical incision or start of the invasive procedure. The initial dose was followed by repeated administration of 75 μg/kg of LR769 every 2 hours (±5 minutes) for the first 48 hours after completion of the procedure. After 48 hours, dosing continued at 75 μg/kg of LR769 (not more frequently than every 2 hours) as follows:

Days 3-4: Intervals up to every 4 hours; Days 5-6: intervals up to every 6 hours; Days 7-10: Intervals up to every 8 hours; Days 11 to last administration of LR769: Intervals up to every 12 hours.

Minor surgical or other invasive procedures were those that usually required <5 days of factor replacement and usually involved the skin, mucous membranes, or superficial connective tissue. The minimum duration of LR769 infusion for minor procedures was 2 days. For less invasive procedures, the patient may have been treated for ≤48 hours if the investigator/designee determined a shorter duration was sufficient to achieve hemostasis.

A dose of 75 μg/kg of LR769 administered within ≤2 minutes of the onset of the procedure was used as the initial dose before the surgical incision or start of the invasive procedure. The initial dose was followed by repeated administration of 75 μg/kg of LR769 every 2 hours (±5 minutes) for the first 48 hours. From Day 3, dosing could continue at 75 μg/kg of LR769 at intervals of up to every 24 hours, but not more frequently than every 2 hours.

Overall Number of Participants Analyzed 4 6
Overall Number of Units Analyzed
Type of Units Analyzed: Surgeries
4 6
Count of Units
Unit of Measure: Surgeries
Successes
4
 100.0%
6
 100.0%
Failures
0
   0.0%
0
   0.0%
3.Secondary Outcome
Title Percentages of Success as Defined as the Combination of "Good" and "Excellent" Responses by the Investigator or Designee
Hide Description Good: postoperative blood loss greater than expected following this type of procedure in a patient who does not have a bleeding disorder and who is undergoing the same surgical or other invasive procedure, not explained by a surgical/medical issue other than hemophilia; no unexpected need for blood component transfusion Excellent: postoperative blood loss similar to or less than expected following this type of procedure in a patient who does not have a bleeding disorder and who is undergoing the same surgical or other invasive procedure; no blood component transfusion is required
Time Frame 72 hours after procedure completion
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population: All patients who received LR769 treatment, underwent a surgical or invasive procedure, and had at least one efficacy assessment.
Arm/Group Title Major Surgery (LR769 Initial Dose 200 μg/kg; Then 75 μg/kg) Minor Surgery (LR769 Initial Dose 75 μg/kg; Then 75 μg/kg)
Hide Arm/Group Description:

Major surgical procedures were those that usually required ≥5 days of factor replacement in hemophilia patients with inhibitors and typically involved entry into a body cavity and/or organ removal or similarly complex procedures.

A dose of 200 μg/kg of LR769 administered within ≤2 minutes of the onset of the procedure was used as the initial dose before the surgical incision or start of the invasive procedure. The initial dose was followed by repeated administration of 75 μg/kg of LR769 every 2 hours (±5 minutes) for the first 48 hours after completion of the procedure. After 48 hours, dosing continued at 75 μg/kg of LR769 (not more frequently than every 2 hours) as follows:

Days 3-4: Intervals up to every 4 hours; Days 5-6: intervals up to every 6 hours; Days 7-10: Intervals up to every 8 hours; Days 11 to last administration of LR769: Intervals up to every 12 hours.

Minor surgical or other invasive procedures were those that usually required <5 days of factor replacement and usually involved the skin, mucous membranes, or superficial connective tissue. The minimum duration of LR769 infusion for minor procedures was 2 days. For less invasive procedures, the patient may have been treated for ≤48 hours if the investigator/designee determined a shorter duration was sufficient to achieve hemostasis.

A dose of 75 μg/kg of LR769 administered within ≤2 minutes of the onset of the procedure was used as the initial dose before the surgical incision or start of the invasive procedure. The initial dose was followed by repeated administration of 75 μg/kg of LR769 every 2 hours (±5 minutes) for the first 48 hours. From Day 3, dosing could continue at 75 μg/kg of LR769 at intervals of up to every 24 hours, but not more frequently than every 2 hours.

Overall Number of Participants Analyzed 5 2
Overall Number of Units Analyzed
Type of Units Analyzed: Surgeries
5 2
Count of Units
Unit of Measure: Surgeries
Successes
5
 100.0%
2
 100.0%
Failures
0
   0.0%
0
   0.0%
Time Frame Adverse Events (AEs) were collected from the time of signing of the informed consent/assent until resolution or 30 days after the last dose of LR769 or early termination, whichever came first.
Adverse Event Reporting Description

An AE was defined as any undesirable physical, psychological, or behavioral effect experienced by a patient or subject during participation in an investigational study, in conjunction with the use of a drug or biologic, whether or not product-related.

Changes in coagulation parameters expected in hemophilia patients were not regarded as AEs, unless they led to clinical measures to prevent or treat any untoward events associated with the deviation of the parameter.

 
Arm/Group Title Major Surgery (LR769 Initial Dose 200 μg/kg; Then 75 μg/kg) Minor Surgery (LR769 Initial Dose 75 μg/kg; Then 75 μg/kg)
Hide Arm/Group Description

Major surgical procedures were those that usually required ≥5 days of factor replacement in hemophilia patients with inhibitors and typically involved entry into a body cavity and/or organ removal or similarly complex procedures.

A dose of 200 μg/kg of LR769 administered within ≤2 minutes of the onset of the procedure was used as the initial dose before the surgical incision or start of the invasive procedure. The initial dose was followed by repeated administration of 75 μg/kg of LR769 every 2 hours (±5 minutes) for the first 48 hours after completion of the procedure. After 48 hours, dosing continued at 75 μg/kg of LR769 (not more frequently than every 2 hours) as follows:

Days 3-4: Intervals up to every 4 hours; Days 5-6: intervals up to every 6 hours; Days 7-10: Intervals up to every 8 hours; Days 11 to last administration of LR769: Intervals up to every 12 hours.

Minor surgical or other invasive procedures were those that usually required <5 days of factor replacement and usually involved the skin, mucous membranes, or superficial connective tissue. The minimum duration of LR769 infusion for minor procedures was 2 days. For less invasive procedures, the patient may have been treated for ≤48 hours if the investigator/designee determined a shorter duration was sufficient to achieve hemostasis.

A dose of 75 μg/kg of LR769 administered within ≤2 minutes of the onset of the procedure was used as the initial dose before the surgical incision or start of the invasive procedure. The initial dose was followed by repeated administration of 75 μg/kg of LR769 every 2 hours (±5 minutes) for the first 48 hours. From Day 3, dosing could continue at 75 μg/kg of LR769 at intervals of up to every 24 hours, but not more frequently than every 2 hours.

All-Cause Mortality
Major Surgery (LR769 Initial Dose 200 μg/kg; Then 75 μg/kg) Minor Surgery (LR769 Initial Dose 75 μg/kg; Then 75 μg/kg)
Affected / at Risk (%) Affected / at Risk (%)
Total   1/6 (16.67%)      0/6 (0.00%)    
Hide Serious Adverse Events
Major Surgery (LR769 Initial Dose 200 μg/kg; Then 75 μg/kg) Minor Surgery (LR769 Initial Dose 75 μg/kg; Then 75 μg/kg)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/6 (16.67%)      0/6 (0.00%)    
Blood and lymphatic system disorders     
Haemorrhagic Anaemia  1  1/6 (16.67%)  1 0/6 (0.00%)  0
Gastrointestinal disorders     
Gastrointestinal Haemorrhage  1  1/6 (16.67%)  1 0/6 (0.00%)  0
1
Term from vocabulary, MedDRA 15.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Major Surgery (LR769 Initial Dose 200 μg/kg; Then 75 μg/kg) Minor Surgery (LR769 Initial Dose 75 μg/kg; Then 75 μg/kg)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/6 (100.00%)      4/6 (66.67%)    
Blood and lymphatic system disorders     
Anaemia  1  2/6 (33.33%)  2 0/6 (0.00%)  0
Gastrointestinal disorders     
Abdominal Pain  1  1/6 (16.67%)  1 0/6 (0.00%)  0
Nausea  1  1/6 (16.67%)  1 0/6 (0.00%)  0
General disorders     
Catheter Site Pain  1  0/6 (0.00%)  0 1/6 (16.67%)  1
Infections and infestations     
Postoperative Wound Infection  1  1/6 (16.67%)  1 0/6 (0.00%)  0
Injury, poisoning and procedural complications     
Anaemia Postoperative  1  2/6 (33.33%)  3 0/6 (0.00%)  0
Post Procedural Haematoma  1  1/6 (16.67%)  1 0/6 (0.00%)  0
Post Procedural Haemorrhage  1  1/6 (16.67%)  2 1/6 (16.67%)  1
Procedural Pain  1  5/6 (83.33%)  7 0/6 (0.00%)  0
Wound Secretion  1  1/6 (16.67%)  2 2/6 (33.33%)  4
Investigations     
C-Reactive Protein Increased  1  1/6 (16.67%)  1 0/6 (0.00%)  0
Metabolism and nutrition disorders     
Decreased Appetite  1  1/6 (16.67%)  1 0/6 (0.00%)  0
Vascular disorders     
Haemorrhage  1  1/6 (16.67%)  1 1/6 (16.67%)  2
Hypertension  1  1/6 (16.67%)  1 0/6 (0.00%)  0
Orthostatic Hypotension  1  1/6 (16.67%)  1 0/6 (0.00%)  0
Phlebitis Superficial  1  1/6 (16.67%)  1 0/6 (0.00%)  0
1
Term from vocabulary, MedDRA 15.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Kerry Biron, Director US Clinical Operations
Organization: LFB USA
Phone: 508.370.5166
EMail: kerry.biron@lfb-usa.com
Layout table for additonal information
Responsible Party: LFB USA, Inc.
ClinicalTrials.gov Identifier: NCT02548143    
Other Study ID Numbers: LFB-FVIIa-008-14
First Submitted: September 9, 2015
First Posted: September 14, 2015
Results First Submitted: August 13, 2019
Results First Posted: September 6, 2019
Last Update Posted: May 14, 2020