Trial Outcomes & Findings for LR769 in Congenital Hemophilia Patients With Inhibitors Undergoing Elective Surgery or Invasive Procedures (NCT NCT02548143)

Last Updated: 2022-02-25

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

12 participants

Primary outcome timeframe

48 (±4) hours after the last administration of LR769

Results posted on

2022-02-25

Participant Flow

Participant milestones

Participant milestones
Measure	Major Surgery (LR769 Initial Dose 200 μg/kg; Then 75 μg/kg) 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 Surgery (LR769 Initial Dose 75 μg/kg; Then 75 μg/kg) 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 Study STARTED	6	6
Overall Study COMPLETED	5	5
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Major Surgery (LR769 Initial Dose 200 μg/kg; Then 75 μg/kg) 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 Surgery (LR769 Initial Dose 75 μg/kg; Then 75 μg/kg) 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 Study Adverse Event	1	0
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Major Surgery (LR769 Initial Dose 200 μg/kg; Then 75 μg/kg) n=6 Participants 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 Surgery (LR769 Initial Dose 75 μg/kg; Then 75 μg/kg) n=6 Participants 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 n=12 Participants Total of all reporting groups
Age, Categorical <=18 years	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	34.0 years STANDARD_DEVIATION 20.19 • n=5 Participants	16.0 years STANDARD_DEVIATION 15.52 • n=7 Participants	25.0 years STANDARD_DEVIATION 19.57 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Ukraine	3 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants
Region of Enrollment South Africa	1 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants
Region of Enrollment Mexico	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment Russia	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Weight	54.17 kg STANDARD_DEVIATION 25.974 • n=5 Participants	36.72 kg STANDARD_DEVIATION 21.506 • n=7 Participants	45.44 kg STANDARD_DEVIATION 24.494 • n=5 Participants
Height	156.3 cm STANDARD_DEVIATION 22.50 • n=5 Participants	137.8 cm STANDARD_DEVIATION 34.02 • n=7 Participants	147.1 cm STANDARD_DEVIATION 29.13 • n=5 Participants
BMI	20.88 kg/ m^2 STANDARD_DEVIATION 6.203 • n=5 Participants	17.61 kg/ m^2 STANDARD_DEVIATION 2.823 • n=7 Participants	19.24 kg/ m^2 STANDARD_DEVIATION 4.902 • n=5 Participants

PRIMARY outcome

Timeframe: 48 (±4) hours after the last administration of LR769

Population: Efficacy Population: All patients who received LR769 treatment, underwent a surgical or invasive procedure, and had at least one efficacy assessment.

Outcome measures

Outcome measures
Measure	Major Surgery (LR769 Initial Dose 200 μg/kg; Then 75 μg/kg) n=6 Surgeries 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 Surgery (LR769 Initial Dose 75 μg/kg; Then 75 μg/kg) n=5 Surgeries 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.
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 Successes	4 Surgeries	5 Surgeries
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 Failures	2 Surgeries	0 Surgeries

SECONDARY outcome

Timeframe: 24 hours after procedure completion

Population: Efficacy Population: All patients who received LR769 treatment, underwent a surgical or invasive procedure, and had at least one efficacy assessment.

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

Outcome measures

Outcome measures
Measure	Major Surgery (LR769 Initial Dose 200 μg/kg; Then 75 μg/kg) n=4 Surgeries 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 Surgery (LR769 Initial Dose 75 μg/kg; Then 75 μg/kg) n=6 Surgeries 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.
Percentages of Success as Defined as the Combination of "Good" and "Excellent" Responses by the Investigator or Designee Successes	4 Surgeries	6 Surgeries
Percentages of Success as Defined as the Combination of "Good" and "Excellent" Responses by the Investigator or Designee Failures	0 Surgeries	0 Surgeries

SECONDARY outcome

Timeframe: 72 hours after procedure completion

Population: Efficacy Population: All patients who received LR769 treatment, underwent a surgical or invasive procedure, and had at least one efficacy assessment.

Outcome measures

Outcome measures
Measure	Major Surgery (LR769 Initial Dose 200 μg/kg; Then 75 μg/kg) n=5 Surgeries 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 Surgery (LR769 Initial Dose 75 μg/kg; Then 75 μg/kg) n=2 Surgeries 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.
Percentages of Success as Defined as the Combination of "Good" and "Excellent" Responses by the Investigator or Designee Successes	5 Surgeries	2 Surgeries
Percentages of Success as Defined as the Combination of "Good" and "Excellent" Responses by the Investigator or Designee Failures	0 Surgeries	0 Surgeries

Adverse Events

Major Surgery (LR769 Initial Dose 200 μg/kg; Then 75 μg/kg)

Serious events: 1 serious events

Other events: 6 other events

Deaths: 1 deaths

Minor Surgery (LR769 Initial Dose 75 μg/kg; Then 75 μg/kg)

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Major Surgery (LR769 Initial Dose 200 μg/kg; Then 75 μg/kg) n=6 participants at risk 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 Surgery (LR769 Initial Dose 75 μg/kg; Then 75 μg/kg) n=6 participants at risk 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.
Blood and lymphatic system disorders Haemorrhagic Anaemia	16.7% 1/6 • Number of events 1 • 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. 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.	0.00% 0/6 • 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. 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.
Gastrointestinal disorders Gastrointestinal Haemorrhage	16.7% 1/6 • Number of events 1 • 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. 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.	0.00% 0/6 • 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. 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.

Other adverse events

Additional Information

Kerry Biron, Director US Clinical Operations

LFB USA

Phone: 508.370.5166

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place