Trial Outcomes & Findings for A Phase III Study on the Safety, Pharmacokinetics and Efficacy of Coagulation Factor VIIa (NCT NCT02448680)
NCT ID: NCT02448680
Last Updated: 2022-02-25
Results Overview
For the primary efficacy endpoint, successful treatment of mild/moderate bleeding episode was defined as meeting all of the following: * "Good" or "excellent" response noted by the patient/parent/legal guardian or other caregiver, depending on patient's age and maturity * Study drug treatment: No further treatment with LR769 beyond timepoint where a "good" or "excellent" response for this bleeding episode was noted * No other hemostatic treatment needed for this bleeding episode * No administration of blood products that would indicate continuation of bleeding beyond timepoint where a "good" or "excellent" response for this bleeding episode was noted * No increase of pain beyond timepoint where a "good" or "excellent" response for this bleeding episode was noted that could not be explained other than as continuation of bleeding
COMPLETED
PHASE3
25 participants
12 hours after first administration of study drug
2022-02-25
Participant Flow
Participant milestones
| Measure |
FVIIa: 75 µg/kg First, Then 225 µg/kg
Coagulation Factor VIIa (Recombinant) : First Intervention (3 months), Second Intervention (3 months), repeat sequence for entirety of study.
|
FVIIa: 225 µg/kg First, Then 75 µg/kg
Coagulation Factor VIIa (Recombinant) : First Intervention (3 months), Second Intervention (3 months), repeat sequence for entirety of study.
|
|---|---|---|
|
Overall Study
STARTED
|
12
|
13
|
|
Overall Study
COMPLETED
|
11
|
10
|
|
Overall Study
NOT COMPLETED
|
1
|
3
|
Reasons for withdrawal
| Measure |
FVIIa: 75 µg/kg First, Then 225 µg/kg
Coagulation Factor VIIa (Recombinant) : First Intervention (3 months), Second Intervention (3 months), repeat sequence for entirety of study.
|
FVIIa: 225 µg/kg First, Then 75 µg/kg
Coagulation Factor VIIa (Recombinant) : First Intervention (3 months), Second Intervention (3 months), repeat sequence for entirety of study.
|
|---|---|---|
|
Overall Study
Physician Decision
|
1
|
1
|
|
Overall Study
Withdrawal by Subject
|
0
|
2
|
Baseline Characteristics
A Phase III Study on the Safety, Pharmacokinetics and Efficacy of Coagulation Factor VIIa
Baseline characteristics by cohort
| Measure |
FVIIa: 75 µg/kg First, Then 225 µg/kg
n=12 Participants
Coagulation Factor VIIa (Recombinant) : First Intervention (3 months), Second Intervention (3 months), repeat sequence for entirety of study.
|
FVIIa: 225 µg/kg First, Then 75 µg/kg
n=13 Participants
Coagulation Factor VIIa (Recombinant) : First Intervention (3 months), Second Intervention (3 months), repeat sequence for entirety of study.
|
Total
n=25 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
4.9 years
STANDARD_DEVIATION 3.02 • n=5 Participants
|
4.8 years
STANDARD_DEVIATION 3.63 • n=7 Participants
|
4.9 years
STANDARD_DEVIATION 3.28 • n=5 Participants
|
|
Age, Customized
Age, Categorical · Birth to < 6 years old
|
6 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Age, Customized
Age, Categorical · >= 6 years to < 12 years old
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
12 Participants
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
|
12 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
11 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
22 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
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
18 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
|
|
Weight
|
19.73 kg
STANDARD_DEVIATION 7.432 • n=5 Participants
|
21.94 kg
STANDARD_DEVIATION 13.391 • n=7 Participants
|
20.88 kg
STANDARD_DEVIATION 10.782 • n=5 Participants
|
|
Height
|
104.21 cm
STANDARD_DEVIATION 21.210 • n=5 Participants
|
108.60 cm
STANDARD_DEVIATION 25.904 • n=7 Participants
|
106.49 cm
STANDARD_DEVIATION 23.382 • n=5 Participants
|
|
Body Mass Index (BMI)
|
17.74 kg/m^2
STANDARD_DEVIATION 2.505 • n=5 Participants
|
17.35 kg/m^2
STANDARD_DEVIATION 3.842 • n=7 Participants
|
17.53 kg/m^2
STANDARD_DEVIATION 3.209 • n=5 Participants
|
PRIMARY outcome
Timeframe: 12 hours after first administration of study drugPopulation: Treated Population
For the primary efficacy endpoint, successful treatment of mild/moderate bleeding episode was defined as meeting all of the following: * "Good" or "excellent" response noted by the patient/parent/legal guardian or other caregiver, depending on patient's age and maturity * Study drug treatment: No further treatment with LR769 beyond timepoint where a "good" or "excellent" response for this bleeding episode was noted * No other hemostatic treatment needed for this bleeding episode * No administration of blood products that would indicate continuation of bleeding beyond timepoint where a "good" or "excellent" response for this bleeding episode was noted * No increase of pain beyond timepoint where a "good" or "excellent" response for this bleeding episode was noted that could not be explained other than as continuation of bleeding
Outcome measures
| Measure |
FVIIa 75 µg/kg
n=239 Bleeding Episodes (BEs)
75 µg/kg Treatment Regimen at Time of Mild/Moderate Bleeding Episode
|
FVIIa 225µg/kg
n=307 Bleeding Episodes (BEs)
225 µg/kg Treatment Regimen at Time of Mild/Moderate Bleeding Episode
|
|---|---|---|
|
Proportion of Successfully Treated Mild/Moderate Bleeding Episodes Per FDA Requirement.
|
0.654 Proportion of successfully treated BEs
Interval 0.523 to 0.785
|
0.603 Proportion of successfully treated BEs
Interval 0.482 to 0.723
|
PRIMARY outcome
Timeframe: 12 hours after first administration of study drugPopulation: Treated Population
* "Good" or "excellent" response noted by the patient/caregiver for mild/moderate bleeding episodes; * "Good" or "excellent" response noted by the physician for severe bleeding episodes.
Outcome measures
| Measure |
FVIIa 75 µg/kg
n=239 Bleeding Episodes (BEs)
75 µg/kg Treatment Regimen at Time of Mild/Moderate Bleeding Episode
|
FVIIa 225µg/kg
n=310 Bleeding Episodes (BEs)
225 µg/kg Treatment Regimen at Time of Mild/Moderate Bleeding Episode
|
|---|---|---|
|
Proportion of Successfully Treated Bleeding Episodes (Mild/Moderate/Severe) Per EMA Definition
|
0.667 Proportion of successfully treated BEs
Interval 0.533 to 0.8
|
0.625 Proportion of successfully treated BEs
Interval 0.5 to 0.75
|
SECONDARY outcome
Timeframe: 12 hour after first administration of study drugPopulation: Treated Population
Based on Patient-Reported "Good" or "Excellent" responses as per the below descriptions: Good: Symptoms of bleed (e.g., swelling, tenderness, and decreased range of motion in the case of musculoskeletal hemorrhage) had largely been reduced by the treatment, but had not completely disappeared. Symptoms had improved enough to not require more infusions of the study drug. Excellent: Full relief of pain and cessation of objective signs of bleed (e.g., swelling, tenderness, and decreased range of motion in the case of musculoskeletal hemorrhage). No additional infusion of study drug was required.
Outcome measures
| Measure |
FVIIa 75 µg/kg
n=239 Bleeding Episodes (BEs)
75 µg/kg Treatment Regimen at Time of Mild/Moderate Bleeding Episode
|
FVIIa 225µg/kg
n=307 Bleeding Episodes (BEs)
225 µg/kg Treatment Regimen at Time of Mild/Moderate Bleeding Episode
|
|---|---|---|
|
Patient-Reported "Good" or "Excellent" Response for Mild/Moderate Bleeding Episodes
|
0.667 Proportion of successfully treated BEs
Interval 0.533 to 0.8
|
0.629 Proportion of successfully treated BEs
Interval 0.502 to 0.756
|
SECONDARY outcome
Timeframe: Within 24 hours of Bleeding EpisodePopulation: Treated Population with non-missing measurements
Categories of Response to Treatment are Described as Follows: None: No noticeable effect of the treatment on the bleed or worsening of patient's condition. Continuation of treatment with the study drug was needed. Moderate: Some effect of the treatment on the bleed was noticed, e.g., pain decreased or bleeding signs improved, but bleed continued and required continued treatment with the study drug. Good: Symptoms of bleed (e.g., swelling, tenderness, and decreased range of motion in the case of musculoskeletal haemorrhage) had largely been reduced by the treatment, but had not completely disappeared. Symptoms had improved enough to not require more infusions of the study drug. Excellent: Full relief of pain and cessation of objective signs of bleed (e.g., swelling, tenderness, and decreased range of motion in the case of musculoskeletal haemorrhage). No additional infusion of study drug was required.
Outcome measures
| Measure |
FVIIa 75 µg/kg
n=233 Bleeding Episodes with Event
75 µg/kg Treatment Regimen at Time of Mild/Moderate Bleeding Episode
|
FVIIa 225µg/kg
n=299 Bleeding Episodes with Event
225 µg/kg Treatment Regimen at Time of Mild/Moderate Bleeding Episode
|
|---|---|---|
|
Time to Patient Assessment of a "Good" or "Excellent" Response for Mild/Moderate Bleeding Episodes
|
9.00 Hours
Interval 8.92 to 11.83
|
12.00 Hours
Interval 11.83 to 12.0
|
SECONDARY outcome
Timeframe: Within 24 hours of Bleeding EpisodePopulation: Treated Population
The number of study drug administrations with non-missing dose information in order to treat one mild/moderate bleeding episode.
Outcome measures
| Measure |
FVIIa 75 µg/kg
n=239 Bleeding Episodes (BEs)
75 µg/kg Treatment Regimen at Time of Mild/Moderate Bleeding Episode
|
FVIIa 225µg/kg
n=307 Bleeding Episodes (BEs)
225 µg/kg Treatment Regimen at Time of Mild/Moderate Bleeding Episode
|
|---|---|---|
|
Number of Administrations of Study Drug Per Mild/Moderate Bleeding Episode
|
3.6 Administrations of Study Drug
Standard Deviation 2.27
|
2.6 Administrations of Study Drug
Standard Deviation 2.48
|
SECONDARY outcome
Timeframe: Within 24 hours of Bleeding EpisodePopulation: Treated Population with non-missing measurements
The total amount of study drug administered in order to treat one mild/moderate bleeding episode.
Outcome measures
| Measure |
FVIIa 75 µg/kg
n=239 Bleeding Episodes (BEs)
75 µg/kg Treatment Regimen at Time of Mild/Moderate Bleeding Episode
|
FVIIa 225µg/kg
n=307 Bleeding Episodes (BEs)
225 µg/kg Treatment Regimen at Time of Mild/Moderate Bleeding Episode
|
|---|---|---|
|
Total Amount of Study Drug Administered Per Mild/Moderate Bleeding Episode
|
6.733 mL per bleeding episode
Standard Deviation 6.3693
|
8.287 mL per bleeding episode
Standard Deviation 5.6531
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 hour after first administration of study drugPopulation: Treated Population
Successful pain relief was defined as a Visual Analogue Scale (VAS: 0-100; 0: no pain at all; 100: the worst pain ever possible) pain score at 12 hours after initial study drug administration that was less than the pain score at the start of treatment with study drug.
Outcome measures
| Measure |
FVIIa 75 µg/kg
n=239 Bleeding Episodes (BEs)
75 µg/kg Treatment Regimen at Time of Mild/Moderate Bleeding Episode
|
FVIIa 225µg/kg
n=307 Bleeding Episodes (BEs)
225 µg/kg Treatment Regimen at Time of Mild/Moderate Bleeding Episode
|
|---|---|---|
|
Mild/Moderate Bleeding Episodes With Successful Pain Relief
|
220 Bleeding Episodes (BEs)
|
275 Bleeding Episodes (BEs)
|
Adverse Events
Coagulation Factor VIIa (Recombinant): 75 µg/kg
Coagulation Factor VIIa (Recombinant): 225 µg/kg
Serious adverse events
| Measure |
Coagulation Factor VIIa (Recombinant): 75 µg/kg
n=23 participants at risk
75 µg/kg treatment regimen for 3 months
Coagulation FVIIa (Recombinant): A cross over design to assess the efficacy of 2 separate dose regimens (75 µg/kg and 225 µg/kg) of Coagulation Factor VIIa (Recombinant) for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to Factor VIII or Factor IX
|
Coagulation Factor VIIa (Recombinant): 225 µg/kg
n=25 participants at risk
225 µg/kg treatment regimen for 3 months
Coagulation FVIIa (Recombinant): A cross over design to assess the efficacy of 2 separate dose regimens (75 µg/kg and 225 µg/kg) of Coagulation Factor VIIa (Recombinant) for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to Factor VIII or Factor IX
|
|---|---|---|
|
Infections and infestations
Dysentery
|
0.00%
0/23 • From signing of the informed consent/assent until resolution or 30 days after the last dose of LR769 or early termination, whichever came first. The average duration for monitoring adverse event is about 11.2 months per patient.
|
4.0%
1/25 • Number of events 1 • From signing of the informed consent/assent until resolution or 30 days after the last dose of LR769 or early termination, whichever came first. The average duration for monitoring adverse event is about 11.2 months per patient.
|
|
Nervous system disorders
Paresis
|
0.00%
0/23 • From signing of the informed consent/assent until resolution or 30 days after the last dose of LR769 or early termination, whichever came first. The average duration for monitoring adverse event is about 11.2 months per patient.
|
4.0%
1/25 • Number of events 1 • From signing of the informed consent/assent until resolution or 30 days after the last dose of LR769 or early termination, whichever came first. The average duration for monitoring adverse event is about 11.2 months per patient.
|
Other adverse events
| Measure |
Coagulation Factor VIIa (Recombinant): 75 µg/kg
n=23 participants at risk
75 µg/kg treatment regimen for 3 months
Coagulation FVIIa (Recombinant): A cross over design to assess the efficacy of 2 separate dose regimens (75 µg/kg and 225 µg/kg) of Coagulation Factor VIIa (Recombinant) for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to Factor VIII or Factor IX
|
Coagulation Factor VIIa (Recombinant): 225 µg/kg
n=25 participants at risk
225 µg/kg treatment regimen for 3 months
Coagulation FVIIa (Recombinant): A cross over design to assess the efficacy of 2 separate dose regimens (75 µg/kg and 225 µg/kg) of Coagulation Factor VIIa (Recombinant) for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to Factor VIII or Factor IX
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
8.7%
2/23 • Number of events 2 • From signing of the informed consent/assent until resolution or 30 days after the last dose of LR769 or early termination, whichever came first. The average duration for monitoring adverse event is about 11.2 months per patient.
|
0.00%
0/25 • From signing of the informed consent/assent until resolution or 30 days after the last dose of LR769 or early termination, whichever came first. The average duration for monitoring adverse event is about 11.2 months per patient.
|
|
Gastrointestinal disorders
Diarrhoea
|
4.3%
1/23 • Number of events 1 • From signing of the informed consent/assent until resolution or 30 days after the last dose of LR769 or early termination, whichever came first. The average duration for monitoring adverse event is about 11.2 months per patient.
|
12.0%
3/25 • Number of events 3 • From signing of the informed consent/assent until resolution or 30 days after the last dose of LR769 or early termination, whichever came first. The average duration for monitoring adverse event is about 11.2 months per patient.
|
|
Gastrointestinal disorders
Vomiting
|
4.3%
1/23 • Number of events 1 • From signing of the informed consent/assent until resolution or 30 days after the last dose of LR769 or early termination, whichever came first. The average duration for monitoring adverse event is about 11.2 months per patient.
|
8.0%
2/25 • Number of events 2 • From signing of the informed consent/assent until resolution or 30 days after the last dose of LR769 or early termination, whichever came first. The average duration for monitoring adverse event is about 11.2 months per patient.
|
|
Infections and infestations
Bronchitis
|
4.3%
1/23 • Number of events 1 • From signing of the informed consent/assent until resolution or 30 days after the last dose of LR769 or early termination, whichever came first. The average duration for monitoring adverse event is about 11.2 months per patient.
|
12.0%
3/25 • Number of events 4 • From signing of the informed consent/assent until resolution or 30 days after the last dose of LR769 or early termination, whichever came first. The average duration for monitoring adverse event is about 11.2 months per patient.
|
|
Infections and infestations
Nasopharyngitis
|
17.4%
4/23 • Number of events 6 • From signing of the informed consent/assent until resolution or 30 days after the last dose of LR769 or early termination, whichever came first. The average duration for monitoring adverse event is about 11.2 months per patient.
|
12.0%
3/25 • Number of events 3 • From signing of the informed consent/assent until resolution or 30 days after the last dose of LR769 or early termination, whichever came first. The average duration for monitoring adverse event is about 11.2 months per patient.
|
|
Infections and infestations
Respiratory tract infection viral
|
4.3%
1/23 • Number of events 2 • From signing of the informed consent/assent until resolution or 30 days after the last dose of LR769 or early termination, whichever came first. The average duration for monitoring adverse event is about 11.2 months per patient.
|
8.0%
2/25 • Number of events 3 • From signing of the informed consent/assent until resolution or 30 days after the last dose of LR769 or early termination, whichever came first. The average duration for monitoring adverse event is about 11.2 months per patient.
|
|
Infections and infestations
Rhinitis
|
13.0%
3/23 • Number of events 3 • From signing of the informed consent/assent until resolution or 30 days after the last dose of LR769 or early termination, whichever came first. The average duration for monitoring adverse event is about 11.2 months per patient.
|
12.0%
3/25 • Number of events 3 • From signing of the informed consent/assent until resolution or 30 days after the last dose of LR769 or early termination, whichever came first. The average duration for monitoring adverse event is about 11.2 months per patient.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
13.0%
3/23 • Number of events 4 • From signing of the informed consent/assent until resolution or 30 days after the last dose of LR769 or early termination, whichever came first. The average duration for monitoring adverse event is about 11.2 months per patient.
|
12.0%
3/25 • Number of events 4 • From signing of the informed consent/assent until resolution or 30 days after the last dose of LR769 or early termination, whichever came first. The average duration for monitoring adverse event is about 11.2 months per patient.
|
Additional Information
Kerry Biron, Director US Clinical Operations
LFB USA, Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place