Trial Outcomes & Findings for Efficacy Study of Activated Prothrombin Complex for Prevention of Bleeds in Hemophilia A With Inhibitors (NCT NCT00221195)

NCT ID: NCT00221195

Last Updated: 2020-03-02

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

34 participants

Primary outcome timeframe

6 months

Results posted on

2020-03-02

Participant Flow

The study was conducted at 16 hemophilia treatment centers in Europe and the United States.

Patients were randomized to one of two 6 month treatment periods. Following the initial treatment period each subject had a 3 month wash-out period during which time they used on-demand therapy to treat bleeding. Following the 3 month wash-out period each patient was crossed-over to the other 6 month treatment period.

Participant milestones

Participant milestones
Measure	On-demand First Patients receive 6 months of on-demand therapy with study drug followed by 6 months of prophylaxis therapy with study drug	Prophylaxis First Patients receive 6 months of prophylaxis therapy with study drug followed by 6 months on-demand therapy with study drug
Therapy 1 (Months 1-6) STARTED	17	17
Therapy 1 (Months 1-6) COMPLETED	14	15
Therapy 1 (Months 1-6) NOT COMPLETED	3	2
Washout Period (Months 7-9) STARTED	14	15
Washout Period (Months 7-9) COMPLETED	14	14
Washout Period (Months 7-9) NOT COMPLETED	0	1
Therapy 2 (Months 10-15) STARTED	14	14
Therapy 2 (Months 10-15) COMPLETED	12	14
Therapy 2 (Months 10-15) NOT COMPLETED	2	0

Reasons for withdrawal

Reasons for withdrawal
Measure	On-demand First Patients receive 6 months of on-demand therapy with study drug followed by 6 months of prophylaxis therapy with study drug	Prophylaxis First Patients receive 6 months of prophylaxis therapy with study drug followed by 6 months on-demand therapy with study drug
Therapy 1 (Months 1-6) Withdrawal by Subject	3	1
Therapy 1 (Months 1-6) Lost to Follow-up	0	1
Washout Period (Months 7-9) Death	0	1
Therapy 2 (Months 10-15) Death	1	0
Therapy 2 (Months 10-15) Adverse Event	1	0

Baseline Characteristics

Efficacy Study of Activated Prothrombin Complex for Prevention of Bleeds in Hemophilia A With Inhibitors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	On-demand First n=17 Participants Patients receive 6 months of on-demand therapy with study drug followed by 6 months of prophylaxis therapy with study drug	Prophylaxis First n=17 Participants Patients receive 6 months of prophylaxis therapy with study drug followed by 6 months on-demand therapy with study drug	Total n=34 Participants Total of all reporting groups
Age, Categorical <=18 years	4 Participants n=93 Participants	7 Participants n=4 Participants	11 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	13 Participants n=93 Participants	9 Participants n=4 Participants	22 Participants n=27 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Age, Continuous	29.3 years STANDARD_DEVIATION 13.4 • n=93 Participants	24.9 years STANDARD_DEVIATION 20.6 • n=4 Participants	27.1 years STANDARD_DEVIATION 17.3 • n=27 Participants
Sex: Female, Male Female	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Sex: Female, Male Male	17 Participants n=93 Participants	17 Participants n=4 Participants	34 Participants n=27 Participants
Region of Enrollment United States	3 participants n=93 Participants	3 participants n=4 Participants	6 participants n=27 Participants
Region of Enrollment Europe	14 participants n=93 Participants	14 participants n=4 Participants	28 participants n=27 Participants

PRIMARY outcome

Timeframe: 6 months

Outcome measures

Outcome measures
Measure	Bleeds During the On-demand Period n=26 Participants During the on-demand period, bleeding was treated with AICC at a target dose of 85 U per kilogram of body weight (±15%) (range, 72 to 98). For bleeding episodes that did not respond to the specified therapy, alternative treatment, including additional doses of AICC, rFVIIa, or factor VIII, was allowed at the discretion of the treating physician. Final analysis only included those who completed per protocol, only 26 subjects completed the study.	Bleeds During the Prophylaxis Period n=26 Participants During the prophylaxis period, AICC was administered at a target dose of 85 U per kilogram (±15%) (range, 72 to 98) on 3 nonconsecutive days weekly. Bleeding episodes during the prophylaxis period were treated with AICC at a target dose of 85 U per kilogram of body weight (±15%) (range, 72 to 98). For bleeding episodes that did not respond to the specified therapy, alternative treatment, including additional doses of AICC, rFVIIa, or factor VIII, was allowed at the discretion of the treating physician. Final analysis only included those who completed per protocol, only 26 subjects completed the study.
Number of Bleeds During 6 Month Treatment Period	13.1 bleeds Standard Deviation 7.1	5.0 bleeds Standard Deviation 5.0

Adverse Events

On-demand Period

Serious events: 3 serious events

Other events: 16 other events

Deaths: 0 deaths

Prophylaxis Period

Serious events: 4 serious events

Other events: 17 other events

Deaths: 0 deaths

Washout Period

Serious events: 4 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	On-demand Period n=31 participants at risk During the on-demand period, bleeding was treated with AICC at a target dose of 85 U per kilogram of body weight (±15%) (range, 72 to 98). For bleeding episodes that did not respond to the specified therapy, alternative treatment, including additional doses of AICC, rFVIIa, or factor VIII, was allowed at the discretion of the treating physician. There were 3 subjects that never received on-demand therapy, therefore 31 subjects were assessed for AEs during this period.	Prophylaxis Period n=31 participants at risk During the prophylaxis period, AICC was administered at a target dose of 85 U per kilogram (±15%) (range, 72 to 98) on 3 nonconsecutive days weekly. Bleeding episodes during the prophylaxis period were treated with AICC at a target dose of 85 U per kilogram of body weight (±15%) (range, 72 to 98). For bleeding episodes that did not respond to the specified therapy, alternative treatment, including additional doses of AICC, rFVIIa, or factor VIII, was allowed at the discretion of the treating physician. There were 3 subjects that never received prophylaxis therapy, therefore 31 subjects were assessed for AEs during this period.	Washout Period n=29 participants at risk Bleeding episodes during the washout period were treated with AICC at a target dose of 85 U per kilogram of body weight (±15%) (range, 72 to 98). For bleeding episodes that did not respond to the specified therapy, alternative treatment, including additional doses of AICC, rFVIIa, or factor VIII, was allowed at the discretion of the treating physician. There were 5 subjects that never entered the washout period, therefore 31 subjects were assessed for AEs during this period.
Cardiac disorders Chest Pain	0.00% 0/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	3.2% 1/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	0.00% 0/29 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.
Musculoskeletal and connective tissue disorders Pain	3.2% 1/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	0.00% 0/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	0.00% 0/29 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.
Product Issues Drug hypersensitivity	0.00% 0/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	3.2% 1/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	0.00% 0/29 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.
Blood and lymphatic system disorders Phlebitis	0.00% 0/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	3.2% 1/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	0.00% 0/29 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.
Endocrine disorders Hospitalization	3.2% 1/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	0.00% 0/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	0.00% 0/29 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.
Surgical and medical procedures Surgical Procedure	3.2% 1/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	0.00% 0/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	0.00% 0/29 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.
Blood and lymphatic system disorders Catheter-site Hemorrhage	3.2% 1/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	3.2% 1/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	0.00% 0/29 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.
Infections and infestations Catheter-site Infection	3.2% 1/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	6.5% 2/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	0.00% 0/29 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.
Infections and infestations Staphylococcal Infection	3.2% 1/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	0.00% 0/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	0.00% 0/29 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.
Vascular disorders Cerebral Hemorrhage	0.00% 0/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	0.00% 0/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	3.4% 1/29 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.
Vascular disorders Subdural Hematoma	0.00% 0/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	0.00% 0/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	3.4% 1/29 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.
Gastrointestinal disorders Gastrointestinal Hemorrhage	0.00% 0/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	3.2% 1/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	0.00% 0/29 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.
Musculoskeletal and connective tissue disorders Joint Swelling	0.00% 0/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	3.2% 1/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	0.00% 0/29 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.
Musculoskeletal and connective tissue disorders Muscle Hemorrhage	0.00% 0/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	0.00% 0/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	6.9% 2/29 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.

Other adverse events

Additional Information

Cindy Leissinger

Tulane University

Phone: 504-988-5433

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	On-demand Period n=31 participants at risk During the on-demand period, bleeding was treated with AICC at a target dose of 85 U per kilogram of body weight (±15%) (range, 72 to 98). For bleeding episodes that did not respond to the specified therapy, alternative treatment, including additional doses of AICC, rFVIIa, or factor VIII, was allowed at the discretion of the treating physician. There were 3 subjects that never received on-demand therapy, therefore 31 subjects were assessed for AEs during this period.	Prophylaxis Period n=31 participants at risk During the prophylaxis period, AICC was administered at a target dose of 85 U per kilogram (±15%) (range, 72 to 98) on 3 nonconsecutive days weekly. Bleeding episodes during the prophylaxis period were treated with AICC at a target dose of 85 U per kilogram of body weight (±15%) (range, 72 to 98). For bleeding episodes that did not respond to the specified therapy, alternative treatment, including additional doses of AICC, rFVIIa, or factor VIII, was allowed at the discretion of the treating physician. There were 3 subjects that never received prophylaxis therapy, therefore 31 subjects were assessed for AEs during this period.	Washout Period n=29 participants at risk Bleeding episodes during the washout period were treated with AICC at a target dose of 85 U per kilogram of body weight (±15%) (range, 72 to 98). For bleeding episodes that did not respond to the specified therapy, alternative treatment, including additional doses of AICC, rFVIIa, or factor VIII, was allowed at the discretion of the treating physician. There were 5 subjects that never entered the washout period, therefore 31 subjects were assessed for AEs during this period.
Blood and lymphatic system disorders Anemia	3.2% 1/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	0.00% 0/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	0.00% 0/29 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.
Musculoskeletal and connective tissue disorders Headache	3.2% 1/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	3.2% 1/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	3.4% 1/29 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.
Musculoskeletal and connective tissue disorders Pain	9.7% 3/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	6.5% 2/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	0.00% 0/29 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.
General disorders Pyrexia	6.5% 2/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	19.4% 6/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	3.4% 1/29 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.
Immune system disorders Drug Hypersensitivity	0.00% 0/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	3.2% 1/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	0.00% 0/29 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.
Immune system disorders Hypersensitivity	6.5% 2/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	0.00% 0/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	0.00% 0/29 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.
Blood and lymphatic system disorders Ecchymosis	6.5% 2/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	9.7% 3/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	3.4% 1/29 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	9.7% 3/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	6.9% 2/29 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.
Infections and infestations Influenza	3.2% 1/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	3.2% 1/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	13.8% 4/29 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.
Respiratory, thoracic and mediastinal disorders Nasopharyngitis	3.2% 1/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	6.5% 2/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	6.9% 2/29 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.
Respiratory, thoracic and mediastinal disorders Pharyngitis	3.2% 1/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	6.5% 2/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	0.00% 0/29 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.
Gastrointestinal disorders Upper Abdominal Pain	0.00% 0/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	3.2% 1/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	3.4% 1/29 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.
Gastrointestinal disorders Vomiting	3.2% 1/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	6.5% 2/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	3.4% 1/29 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.
Surgical and medical procedures Poor Venous Access	0.00% 0/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	3.2% 1/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	0.00% 0/29 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.
Blood and lymphatic system disorders Catheter-site Hemorrhage	3.2% 1/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	6.5% 2/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	0.00% 0/29 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.
Infections and infestations Catheter-site Infection	3.2% 1/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	6.5% 2/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	0.00% 0/29 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.
Infections and infestations Staphylococcal Infection	3.2% 1/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	0.00% 0/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	0.00% 0/29 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.
Blood and lymphatic system disorders Tongue Hemorrhage	3.2% 1/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	0.00% 0/31 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.	3.4% 1/29 • Adverse events were collected from time of consent to the end of the study, which totaled 15 months.