Trial Outcomes & Findings for Recombinant Factor VIIa BI (rFVIIa BI) Treatment of Acute Bleeding Episodes Per an On-demand Regimen (NCT NCT01757405)

NCT ID: NCT01757405

Last Updated: 2021-05-11

Results Overview

No additional hemostatic product required within 12 hours of first dose other than the prescribed dosing regimen.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 40 participants
• Primary outcome timeframe: within 12 hours of first dose
• Results posted on: 2021-05-11

Participant Flow

Enrollment was conduced at 16 clinical sites from the following countries: Japan, Taiwan, Poland, Romania, Russian Federation, Serbia, Spain, Ukraine and the United States.

40 participants provided informed consent and were screened for study participation, of which there was 1 screen failure. 39 participants (in pre-assignment period) were randomized where 1 participant withdrew after randomization but prior to treatment, therefore 38 participants were treated with recombinant activated factor VII BI (rFVIIa).

Participant milestones

Measure	Arm 1: up to 3 x 90 Micrograms/kg rFVIIa BI Bleeding episodes treated with up to 3 doses of 90 micrograms/kg of recombinant activated factor VII BI (rFVIIaBI) every 3 hours as on-demand intravenous bolus infusions.	Arm 2: 1 x 270 Micrograms/kg rFVIIa BI Bleeding episodes treated with 1 dose of 270 micrograms/kg of recombinant activated factor VII BI (rFVIIa BI) as on-demand intravenous bolus infusion.
Overall Study STARTED	18	20
Overall Study COMPLETED	17	18
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Measure	Arm 1: up to 3 x 90 Micrograms/kg rFVIIa BI Bleeding episodes treated with up to 3 doses of 90 micrograms/kg of recombinant activated factor VII BI (rFVIIaBI) every 3 hours as on-demand intravenous bolus infusions.	Arm 2: 1 x 270 Micrograms/kg rFVIIa BI Bleeding episodes treated with 1 dose of 270 micrograms/kg of recombinant activated factor VII BI (rFVIIa BI) as on-demand intravenous bolus infusion.
Overall Study Lost to Follow-up	1	1
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Recombinant Factor VIIa BI (rFVIIa BI) Treatment of Acute Bleeding Episodes Per an On-demand Regimen

Baseline characteristics by cohort

Measure	Arm 1: up to 3 x 90 Micrograms/kg rFVIIa BI n=18 Participants Bleeding episodes treated with up to 3 doses of 90 micrograms/kg of recombinant activated factor VII BI (rFVIIaBI) every 3 hours as on-demand intravenous bolus infusions.	Arm 2: 1 x 270 Micrograms/kg rFVIIa BI n=20 Participants Bleeding episodes treated with 1 dose of 270 micrograms/kg of recombinant activated factor VII BI (rFVIIa BI) as on-demand intravenous bolus infusion.	Total n=38 Participants Total of all reporting groups
Age, Continuous	28 Years n=5 Participants	28 Years n=7 Participants	28 Years 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	18 Participants n=5 Participants	20 Participants n=7 Participants	38 Participants n=5 Participants

PRIMARY outcome

Timeframe: within 12 hours of first dose

Population: Full Analysis Dataset

No additional hemostatic product required within 12 hours of first dose other than the prescribed dosing regimen.

Outcome measures

Measure	Arm 1: up to 3 x 90 Micrograms/kg rFVIIa BI n=289 Bleeding Episodes Bleeding episodes treated with up to 3 doses of 90 micrograms/kg of recombinant activated factor VII BI (rFVIIaBI) every 3 hours as on-demand intravenous bolus infusions.	Arm 2: 1 x 270 Micrograms/kg rFVIIa BI n=256 Bleeding Episodes Bleeding episodes treated with 1 dose of 270 micrograms/kg of recombinant activated factor VII BI (rFVIIa BI) as on-demand intravenous bolus infusion.
Percentage of Bleeding Episode With "Treatment Success"	96.19 percent of bleeding episodes Interval 93.31 to 97.86	79.30 percent of bleeding episodes Interval 73.92 to 83.81

SECONDARY outcome

Timeframe: within 24 hours of infusion

Population: Full Analysis Dataset

Participants rated the treatment of each bleeding episode. If treatment occurred under direct supervision of treating physician, the physician rated the response. Ratings based on a 4 point scale; EXCELLENT - full relief of pain and cessation of objective signs of bleeding (swelling, tenderness, decrease in range of motion [for muscle bleeds]) within 9 hours of treatment initiation. No additional infusion required to control bleeding, other than prescribed dosing regimen. GOOD - Substantial relief of pain and/or cessation of objective signs of bleeding within 9 hours of treatment initiation. No additional infusion required to control bleeding, other than prescribed dosing regimen. MODERATE - slight relief of pain and slight improvement of signs of bleeding within 9 hours of treatment initiation. Requires additional infusion beyond treatment regimen. NONE - No improvement or condition worsens. SUCCESSFUL = EXCELLENT or GOOD.

Outcome measures

Measure	Arm 1: up to 3 x 90 Micrograms/kg rFVIIa BI n=289 Bleeding Episodes Bleeding episodes treated with up to 3 doses of 90 micrograms/kg of recombinant activated factor VII BI (rFVIIaBI) every 3 hours as on-demand intravenous bolus infusions.	Arm 2: 1 x 270 Micrograms/kg rFVIIa BI n=256 Bleeding Episodes Bleeding episodes treated with 1 dose of 270 micrograms/kg of recombinant activated factor VII BI (rFVIIa BI) as on-demand intravenous bolus infusion.
Treatment Response for Each Bleeding Episode Successful	87.89 percent of bleeding episodes Interval 83.62 to 91.16	79.30 percent of bleeding episodes Interval 73.92 to 83.81
Treatment Response for Each Bleeding Episode Excellent	34.60 percent of bleeding episodes Interval 29.35 to 40.26	36.72 percent of bleeding episodes Interval 31.05 to 42.78
Treatment Response for Each Bleeding Episode Good	53.29 percent of bleeding episodes Interval 47.53 to 58.96	42.58 percent of bleeding episodes Interval 36.67 to 48.7
Treatment Response for Each Bleeding Episode Moderate	9.69 percent of bleeding episodes Interval 6.79 to 13.65	18.36 percent of bleeding episodes Interval 14.1 to 23.56
Treatment Response for Each Bleeding Episode No Assessment Available	0 percent of bleeding episodes Interval 0.0 to 0.0	0.39 percent of bleeding episodes Interval 0.07 to 2.18
Treatment Response for Each Bleeding Episode None	2.42 percent of bleeding episodes Interval 1.18 to 4.91	1.95 percent of bleeding episodes Interval 0.84 to 4.49

SECONDARY outcome

Timeframe: 24 hours post infusion

Population: Full Analysis Dataset

Clinical responders defined as sustained bleeding control, (no additional hemostatic medication including rFVIIa BI required between 12 and 24 hours after first infusion of the successfully treated bleeding episode).

Outcome measures

Measure	Arm 1: up to 3 x 90 Micrograms/kg rFVIIa BI n=289 Bleeding Episodes Bleeding episodes treated with up to 3 doses of 90 micrograms/kg of recombinant activated factor VII BI (rFVIIaBI) every 3 hours as on-demand intravenous bolus infusions.	Arm 2: 1 x 270 Micrograms/kg rFVIIa BI n=256 Bleeding Episodes Bleeding episodes treated with 1 dose of 270 micrograms/kg of recombinant activated factor VII BI (rFVIIa BI) as on-demand intravenous bolus infusion.
Percentage of Clinical Responders (Sustained Bleeding Control) for All Acute Bleeding Episodes	93.43 percent of bleeding episodes Interval 89.96 to 95.75	76.17 percent of bleeding episodes Interval 70.59 to 80.98

SECONDARY outcome

Timeframe: 6 months (throughout study period)

Population: Safety Analysis Dataset

Safety was determined by the number of AEs (both serious AEs [SAEs] and non-serious AEs [nsAE]). Tolerability was determined by the number of AEs related to rFVIIa BI (both SAEs and nsAEs) as determined by causality assessment of the AEs by the investigator. An AE was deemed Related if the investigator judged the AE to be "possibly related" or "probably related" to rFVIIa BI. The percentage of participants with AEs were presented by seriousness (SAE, nsAE), severity (Mild, Moderate or Severe) and causality (Related or Not Related to rFVIIa BI).

Outcome measures

Measure	Arm 1: up to 3 x 90 Micrograms/kg rFVIIa BI n=18 Participants Bleeding episodes treated with up to 3 doses of 90 micrograms/kg of recombinant activated factor VII BI (rFVIIaBI) every 3 hours as on-demand intravenous bolus infusions.	Arm 2: 1 x 270 Micrograms/kg rFVIIa BI n=20 Participants Bleeding episodes treated with 1 dose of 270 micrograms/kg of recombinant activated factor VII BI (rFVIIa BI) as on-demand intravenous bolus infusion.
Safety and Tolerability of Treatment Regimens by Clinical Assessment of Percentage of Participants With Adverse Events (AEs) SAE-Moderate-Unrelated	5.6 percent of participants with AEs	5.0 percent of participants with AEs
Safety and Tolerability of Treatment Regimens by Clinical Assessment of Percentage of Participants With Adverse Events (AEs) SAE-Severe-Unrelated	11.1 percent of participants with AEs	0 percent of participants with AEs
Safety and Tolerability of Treatment Regimens by Clinical Assessment of Percentage of Participants With Adverse Events (AEs) SAE-Severe-Related	0 percent of participants with AEs	5.0 percent of participants with AEs
Safety and Tolerability of Treatment Regimens by Clinical Assessment of Percentage of Participants With Adverse Events (AEs) nsAE-Mild-Unrelated	22.2 percent of participants with AEs	30.0 percent of participants with AEs
Safety and Tolerability of Treatment Regimens by Clinical Assessment of Percentage of Participants With Adverse Events (AEs) nsAE-Moderate-Unrelated	0 percent of participants with AEs	15.0 percent of participants with AEs

SECONDARY outcome

Timeframe: 6 months (throughout study period)

Population: Safety Analysis Dataset

Safety was determined by the number of AEs (both serious AEs [SAEs] and non-serious AEs [nsAE]). Tolerability was determined by the number of AEs related to rFVIIa BI (both SAEs and nsAEs) as determined by causality assessment of the AEs by the investigator. An AE was deemed Related if the investigator judges the AE to be "possibly related" or "probably related" to rFVIIa BI. The percentage of AEs were presented by seriousness (SAE, nsAE), severity (Mild, Moderate or Severe) and causality (Related or Not Related [to rFVIIa BI]).

Outcome measures

Measure	Arm 1: up to 3 x 90 Micrograms/kg rFVIIa BI n=15 adverse events Bleeding episodes treated with up to 3 doses of 90 micrograms/kg of recombinant activated factor VII BI (rFVIIaBI) every 3 hours as on-demand intravenous bolus infusions.	Arm 2: 1 x 270 Micrograms/kg rFVIIa BI n=16 adverse events Bleeding episodes treated with 1 dose of 270 micrograms/kg of recombinant activated factor VII BI (rFVIIa BI) as on-demand intravenous bolus infusion.
Safety and Tolerability of Treatment Regimens by Clinical Assessment of Adverse Events (AEs) SAE-Moderate-Unrelated	6.7 percent of AEs	6.3 percent of AEs
Safety and Tolerability of Treatment Regimens by Clinical Assessment of Adverse Events (AEs) SAE-Severe-Unrelated	20.0 percent of AEs	0 percent of AEs
Safety and Tolerability of Treatment Regimens by Clinical Assessment of Adverse Events (AEs) SAE-Severe-Related	0 percent of AEs	12.5 percent of AEs
Safety and Tolerability of Treatment Regimens by Clinical Assessment of Adverse Events (AEs) nsAE-Mild-Unrelated	73.3 percent of AEs	62.5 percent of AEs
Safety and Tolerability of Treatment Regimens by Clinical Assessment of Adverse Events (AEs) nsAE-Moderate-Unrelated	0 percent of AEs	18.8 percent of AEs

SECONDARY outcome

Timeframe: 6 months (throughout study period)

Population: Safety Analysis Dataset

Development of rFVII inhibitors or FVIIa binding antibodies during the study.

Outcome measures

Measure	Arm 1: up to 3 x 90 Micrograms/kg rFVIIa BI n=18 Participants Bleeding episodes treated with up to 3 doses of 90 micrograms/kg of recombinant activated factor VII BI (rFVIIaBI) every 3 hours as on-demand intravenous bolus infusions.	Arm 2: 1 x 270 Micrograms/kg rFVIIa BI n=20 Participants Bleeding episodes treated with 1 dose of 270 micrograms/kg of recombinant activated factor VII BI (rFVIIa BI) as on-demand intravenous bolus infusion.
Percentage of Participants With Inhibitor Development to FVII	0 percent of participants	0 percent of participants

Adverse Events

Arm 1: up to 3 x 90 Micrograms/kg rFVIIa BI

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

Arm 2: 1 x 270 Micrograms/kg rFVIIa BI

Serious events: 2 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Measure	Arm 1: up to 3 x 90 Micrograms/kg rFVIIa BI n=18 participants at risk Bleeding episodes treated with up to 3 doses of 90 micrograms/kg of recombinant activated factor VII BI (rFVIIa BI) every 3 hours as on-demand intravenous bolus infusions.	Arm 2: 1 x 270 Micrograms/kg rFVIIa BI n=20 participants at risk Bleeding episodes treated with 1 dose of 270 micrograms/kg of recombinant activated factor VII BI (rFVIIa BI) as on-demand intravenous bolus infusion.
Injury, poisoning and procedural complications Craniocerebral injury	5.6% 1/18 • Number of events 1 • 6 months (throughout study period)	0.00% 0/20 • 6 months (throughout study period)
Injury, poisoning and procedural complications Joint injury	5.6% 1/18 • Number of events 1 • 6 months (throughout study period)	0.00% 0/20 • 6 months (throughout study period)
Injury, poisoning and procedural complications Head Injury	5.6% 1/18 • Number of events 1 • 6 months (throughout study period)	0.00% 0/20 • 6 months (throughout study period)
Injury, poisoning and procedural complications Limb Injury	5.6% 1/18 • Number of events 1 • 6 months (throughout study period)	0.00% 0/20 • 6 months (throughout study period)
General disorders Drug Ineffective	0.00% 0/18 • 6 months (throughout study period)	5.0% 1/20 • Number of events 1 • 6 months (throughout study period)
Musculoskeletal and connective tissue disorders Muscle Haemorrhage	0.00% 0/18 • 6 months (throughout study period)	10.0% 2/20 • Number of events 2 • 6 months (throughout study period)

Other adverse events

Measure	Arm 1: up to 3 x 90 Micrograms/kg rFVIIa BI n=18 participants at risk Bleeding episodes treated with up to 3 doses of 90 micrograms/kg of recombinant activated factor VII BI (rFVIIa BI) every 3 hours as on-demand intravenous bolus infusions.	Arm 2: 1 x 270 Micrograms/kg rFVIIa BI n=20 participants at risk Bleeding episodes treated with 1 dose of 270 micrograms/kg of recombinant activated factor VII BI (rFVIIa BI) as on-demand intravenous bolus infusion.
Injury, poisoning and procedural complications Laceration	5.6% 1/18 • Number of events 1 • 6 months (throughout study period)	0.00% 0/20 • 6 months (throughout study period)
Investigations Hepatic Enzyme Increased	5.6% 1/18 • Number of events 1 • 6 months (throughout study period)	0.00% 0/20 • 6 months (throughout study period)
Respiratory, thoracic and mediastinal disorders Nasal Congestion	5.6% 1/18 • Number of events 1 • 6 months (throughout study period)	0.00% 0/20 • 6 months (throughout study period)
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	5.6% 1/18 • Number of events 2 • 6 months (throughout study period)	0.00% 0/20 • 6 months (throughout study period)
Immune system disorders Drug Hypersensitivity	5.6% 1/18 • Number of events 1 • 6 months (throughout study period)	0.00% 0/20 • 6 months (throughout study period)
Nervous system disorders Headache	5.6% 1/18 • Number of events 1 • 6 months (throughout study period)	0.00% 0/20 • 6 months (throughout study period)
Nervous system disorders Sinus Headache	5.6% 1/18 • Number of events 1 • 6 months (throughout study period)	0.00% 0/20 • 6 months (throughout study period)
General disorders Pyrexia	5.6% 1/18 • Number of events 1 • 6 months (throughout study period)	0.00% 0/20 • 6 months (throughout study period)
Infections and infestations Influenza	0.00% 0/18 • 6 months (throughout study period)	10.0% 2/20 • Number of events 2 • 6 months (throughout study period)
Infections and infestations Nasopharyngitis	5.6% 1/18 • Number of events 1 • 6 months (throughout study period)	0.00% 0/20 • 6 months (throughout study period)
Infections and infestations Tinea Versicolour	5.6% 1/18 • Number of events 1 • 6 months (throughout study period)	0.00% 0/20 • 6 months (throughout study period)

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: ClinicalTransparency@shire.com

Results disclosure agreements

• Principal investigator is a sponsor employee Baxalta's agreements with PIs may vary per requirements of individual PI, but contain common elements. For this study, results may not be published without prior written approval of Sponsor.
• Publication restrictions are in place

Restriction type: OTHER