Trial Outcomes & Findings for Phase III Study of Coagulation FVIIa (Recombinant) in Congenital Hemophilia A or B Patients With Inhibitors (NCT NCT02020369)
NCT ID: NCT02020369
Last Updated: 2017-06-14
Results Overview
For the primary efficacy endpoint, successful treatment of a bleeding episode was defined as a combination of the following: * "Good" or "Excellent" response noted by the patient * Study drug treatment: No further treatment with study drug beyond timepoint for this bleeding episode * No other hemostatic treatment needed for this bleeding episode * No administration of blood products that would indicate continuation of bleeding beyond timepoint * No increase of pain beyond timepoint that could not otherwise be explained
COMPLETED
PHASE3
27 participants
12 hours after first administration of study drug
2017-06-14
Participant Flow
Participant milestones
| Measure |
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.
|
FVIIa: 75 µg/kg First, Then 225 µg/kg
Coagulation Factor VIIa (Recombinant): Coagulation Factor VIIa (Recombinant) : First Intervention (3 months), Second Intervention (3 months), repeat sequence for entirety of study.
|
|---|---|---|
|
Overall Study
STARTED
|
14
|
13
|
|
Overall Study
COMPLETED
|
11
|
11
|
|
Overall Study
NOT COMPLETED
|
3
|
2
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Phase III Study of Coagulation FVIIa (Recombinant) in Congenital Hemophilia A or B Patients With Inhibitors
Baseline characteristics by cohort
| Measure |
FVIIa 75 µg/kg First, Then 225 µg/kg
n=13 Participants
Coagulation Factor VIIa (Recombinant): First Intervention (3 months), Second Intervention (3 months), continue cycle until end of study.
|
FVIIa 225 µg/kg First, Then 75 µg/kg
n=14 Participants
Coagulation Factor VIIa (Recombinant): First Intervention (3 months), Second Intervention (3 months), continue cycle until end of study.
|
Total
n=27 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
11 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
22 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
|
31.8 years
STANDARD_DEVIATION 12.10 • n=5 Participants
|
30.1 years
STANDARD_DEVIATION 12.98 • n=7 Participants
|
31.0 years
STANDARD_DEVIATION 12.35 • n=5 Participants
|
|
Sex/Gender, Customized
Male (n)
|
13 participants
n=5 Participants
|
14 participants
n=7 Participants
|
27 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
|
12 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
26 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
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 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
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
12 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
25 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
Russian Federation
|
2 participants
n=5 Participants
|
3 participants
n=7 Participants
|
5 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
2 participants
n=5 Participants
|
2 participants
n=7 Participants
|
4 participants
n=5 Participants
|
|
Region of Enrollment
Ukraine
|
6 participants
n=5 Participants
|
6 participants
n=7 Participants
|
12 participants
n=5 Participants
|
|
Region of Enrollment
Poland
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Region of Enrollment
Georgia
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Region of Enrollment
Bulgaria
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 12 hours after first administration of study drugPopulation: Treated Population
For the primary efficacy endpoint, successful treatment of a bleeding episode was defined as a combination of the following: * "Good" or "Excellent" response noted by the patient * Study drug treatment: No further treatment with study drug beyond timepoint for this bleeding episode * No other hemostatic treatment needed for this bleeding episode * No administration of blood products that would indicate continuation of bleeding beyond timepoint * No increase of pain beyond timepoint that could not otherwise be explained
Outcome measures
| Measure |
FVIIa 75 µg/kg
n=252 Bleeding Episodes (BEs)
75 µg/kg Treatment Regimen at Time of Mild/Moderate Bleeding Episode
|
FVIIa 225µg/kg
n=213 Bleeding Episodes (BEs)
225 µg/kg Treatment Regimen at Time of Mild/Moderate Bleeding Episode
|
|---|---|---|
|
Proportion of Successfully Treated Mild/Moderate Bleeding Episodes
|
.849 Proportion of Success of BEs
Interval 0.74 to 0.957
|
.932 Proportion of Success of BEs
Interval 0.881 to 0.983
|
SECONDARY outcome
Timeframe: at 12 hoursPopulation: 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 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=252 Bleeding Episodes (BEs)
75 µg/kg Treatment Regimen at Time of Mild/Moderate Bleeding Episode
|
FVIIa 225µg/kg
n=213 Bleeding Episodes (BEs)
225 µg/kg Treatment Regimen at Time of Mild/Moderate Bleeding Episode
|
|---|---|---|
|
Proportion of Mild/Moderate Bleeding Episodes With Patient (Pt)-Reported "Good" or "Excellent" Responses at 12 Hours
|
0.857 Pt-reported proportion success of BEs
Interval 0.75 to 0.964
|
0.937 Pt-reported proportion success of BEs
Interval 0.888 to 0.986
|
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=240 Bleeding Episodes with event
75 µg/kg Treatment Regimen at Time of Mild/Moderate Bleeding Episode
|
FVIIa 225µg/kg
n=208 Bleeding Episodes with event
225 µg/kg Treatment Regimen at Time of Mild/Moderate Bleeding Episode
|
|---|---|---|
|
Time to Assessment of a "Good" or "Excellent" Response of Mild/Moderate Bleeding Episodes by the Patient
|
5.98 Hours
Interval 5.95 to 6.0
|
3.00 Hours
The confidence interval (CI) for the median time is a pointwise CI. The median was 3 hours and approximately 30% of bleeding episodes had good/excellent response exactly at 3 hours which made the confidence limits non-calculable.
|
SECONDARY outcome
Timeframe: Within 24 hours of Bleeding EpisodePopulation: Treated Population with non-missing measurements
Outcome measures
| Measure |
FVIIa 75 µg/kg
n=252 Bleeding episodes
75 µg/kg Treatment Regimen at Time of Mild/Moderate Bleeding Episode
|
FVIIa 225µg/kg
n=211 Bleeding episodes
225 µg/kg Treatment Regimen at Time of Mild/Moderate Bleeding Episode
|
|---|---|---|
|
Number of Administrations of Study Drug Per Mild/Moderate Bleeding Episode
|
2.5 Number of Administrations of Study Drug
Standard Deviation 1.75
|
1.4 Number of Administrations of Study Drug
Standard Deviation 0.96
|
SECONDARY outcome
Timeframe: Through study completionPopulation: Treated Population with non-missing measurements
Outcome measures
| Measure |
FVIIa 75 µg/kg
n=251 Bleeding Episodes
75 µg/kg Treatment Regimen at Time of Mild/Moderate Bleeding Episode
|
FVIIa 225µg/kg
n=211 Bleeding Episodes
225 µg/kg Treatment Regimen at Time of Mild/Moderate Bleeding Episode
|
|---|---|---|
|
Total Amount of Study Drug Administered Per Mild/Moderate Bleeding Episode
|
187.868 µg/kg per bleeding episode
Standard Deviation 131.7982
|
252.963 µg/kg per bleeding episode
Standard Deviation 78.9732
|
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=25 participants at risk
Coagulation Factor VIIa (Recombinant): 75 µg/kg for 3 months
Coagulation Factor VIIa (Recombinant): A cross over design to assess the efficacy of 2 separate dose regimens (75µg/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/IX
|
Coagulation Factor VIIa (Recombinant): 225 µg/kg
n=25 participants at risk
Coagulation Factor VIIa (Recombinant) : 225 µg/kg for 3 months
Coagulation Factor VIIa (Recombinant): A cross over design to assess the efficacy of 2 separate dose regimens (75µg/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/IX
|
|---|---|---|
|
Infections and infestations
acute tonsillitis
|
4.0%
1/25 • Number of events 1 • Adverse event data was collected 2 years, 3 months, 2 days
|
0.00%
0/25 • Adverse event data was collected 2 years, 3 months, 2 days
|
|
Nervous system disorders
subarachnoid hemorrhage
|
4.0%
1/25 • Number of events 1 • Adverse event data was collected 2 years, 3 months, 2 days
|
0.00%
0/25 • Adverse event data was collected 2 years, 3 months, 2 days
|
Other adverse events
| Measure |
Coagulation Factor VIIa (Recombinant): 75 µg/kg
n=25 participants at risk
Coagulation Factor VIIa (Recombinant): 75 µg/kg for 3 months
Coagulation Factor VIIa (Recombinant): A cross over design to assess the efficacy of 2 separate dose regimens (75µg/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/IX
|
Coagulation Factor VIIa (Recombinant): 225 µg/kg
n=25 participants at risk
Coagulation Factor VIIa (Recombinant) : 225 µg/kg for 3 months
Coagulation Factor VIIa (Recombinant): A cross over design to assess the efficacy of 2 separate dose regimens (75µg/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/IX
|
|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
4.0%
1/25 • Number of events 1 • Adverse event data was collected 2 years, 3 months, 2 days
|
8.0%
2/25 • Number of events 2 • Adverse event data was collected 2 years, 3 months, 2 days
|
|
Nervous system disorders
Headache
|
8.0%
2/25 • Number of events 3 • Adverse event data was collected 2 years, 3 months, 2 days
|
4.0%
1/25 • Number of events 1 • Adverse event data was collected 2 years, 3 months, 2 days
|
Additional Information
Jeffry Lawrence, MD, Vice President, Clinical Development
LFB USA Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60