LR769 in Congenital Hemophilia Patients With Inhibitors Undergoing Elective Surgery or Invasive Procedures (PerSept3)

• ClinicalTrials.gov Identifier: NCT02548143
• Recruitment Status: Completed
• First Posted: September 14, 2015
• Results First Posted: September 6, 2019
• Last Update Posted: February 25, 2022
• Sponsor: Laboratoire français de Fractionnement et de Biotechnologies
• Collaborator: LFB USA, Inc.
• Information provided by (Responsible Party): Laboratoire français de Fractionnement et de Biotechnologies

• 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

Participant Flow

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)
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

Baseline Characteristics

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
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
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)

Outcome Measures

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
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

Outcome Measure Data

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)
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
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

Outcome Measure Data

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)
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
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

Outcome Measure Data

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)
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%

Adverse Events

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)
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%)
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
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

Limitations and Caveats

[Not Specified]

More Information

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

• Name/Title: Kerry Biron, Director US Clinical Operations
• Organization: LFB USA
• Phone: 508.370.5166
• EMail: kerry.biron@lfb-usa.com

• Responsible Party: Laboratoire français de Fractionnement et de Biotechnologies
• 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: February 25, 2022