Trial Outcomes & Findings for Hemophilia Adult Prophylaxis Study: Factor VIII in Severe Hemophilia A (NCT NCT01405742)

NCT ID: NCT01405742

Last Updated: 2016-10-07

Results Overview

The primary outcome was bleed frequency. The data were total number of events for each Arm, and not per-participant.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 4 participants
• Primary outcome timeframe: Weeks 26 (first intervention) and 52 (second intervention)
• Results posted on: 2016-10-07

Participant Flow

Following enrollment, subjects initiated study drug according to the randomization to Arm A (once-weekly FVIII) or Arm B (thrice-weekly FVIII) for a 26 week period followed by a 72 hour washout period prior to crossover to the other arm for the second 26 week period.

Participant milestones

Measure	Once-Weekly Then Thrice-Weekly FVIII Subjects randomized to receive either once-weekly F.VIII at 40 IU/kg (Arm A) or thrice-weekly F.VIII at 40 IU/kg (Arm B) for the first 26 weeks of study. Then, at 26 weeks, they will undergo "Cross-Over", that is, switch to the alternative Study Arm for the last 26 weeks, following a 72 hour washout period. Group 1, will receive Arm A for the first 26 weeks, and Arm B for the last 26 weeks. Group 2, will receive Arm B for the first 26 weeks and Arm A for the last 26 weeks.	Thrice-Weekly Then Once-Weekly FVIII Subjects randomized to receive either once-weekly F.VIII at 40 IU/kg (Arm A) or thrice-weekly F.VIII at 40 IU/kg (Arm B) for the first 26 weeks of study. Then, at 26 weeks, they will undergo "Cross-Over", that is, switch to the alternative Study Arm for the last 26 weeks, following a 72 hour washout period. Group 1, will receive Arm A for the first 26 weeks, and Arm B for the last 26 weeks. Group 2, will receive Arm B for the first 26 weeks and Arm A for the last 26 weeks.
Overall Study STARTED	2	2
Overall Study COMPLETED	1	2
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Measure	Once-Weekly Then Thrice-Weekly FVIII Subjects randomized to receive either once-weekly F.VIII at 40 IU/kg (Arm A) or thrice-weekly F.VIII at 40 IU/kg (Arm B) for the first 26 weeks of study. Then, at 26 weeks, they will undergo "Cross-Over", that is, switch to the alternative Study Arm for the last 26 weeks, following a 72 hour washout period. Group 1, will receive Arm A for the first 26 weeks, and Arm B for the last 26 weeks. Group 2, will receive Arm B for the first 26 weeks and Arm A for the last 26 weeks.	Thrice-Weekly Then Once-Weekly FVIII Subjects randomized to receive either once-weekly F.VIII at 40 IU/kg (Arm A) or thrice-weekly F.VIII at 40 IU/kg (Arm B) for the first 26 weeks of study. Then, at 26 weeks, they will undergo "Cross-Over", that is, switch to the alternative Study Arm for the last 26 weeks, following a 72 hour washout period. Group 1, will receive Arm A for the first 26 weeks, and Arm B for the last 26 weeks. Group 2, will receive Arm B for the first 26 weeks and Arm A for the last 26 weeks.
Overall Study Lost to Follow-up	1	0

Baseline Characteristics

Hemophilia Adult Prophylaxis Study: Factor VIII in Severe Hemophilia A

Baseline characteristics by cohort

Measure	Severe Hemophilia A n=3 Participants Subjects will be randomized to receive either once-weekly F.VIII at 40 IU/kg (Arm A) or thrice-weekly F.VIII at 40 IU/kg (Arm B) for the first 26 weeks of study. Then, at 26 weeks, they will undergo "Cross-Over", that is, switch to the alternative Study Arm for the last 26 weeks, following a 72 hour washout period.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	25.5 year n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants
Region of Enrollment United States	3 participants n=5 Participants

PRIMARY outcome

Timeframe: Weeks 26 (first intervention) and 52 (second intervention)

Population: 3 completing study were analyzed

The primary outcome was bleed frequency. The data were total number of events for each Arm, and not per-participant.

Outcome measures

Measure	Once Weekly FVIII n=3 Participants Subjects will be randomized to receive once-weekly FVIII at 40 IU/kg (Arm A) for the first 26 weeks. Then at 26 weeks, they will cross-over to thrice-weekly FVIII at 40 IU/kg (Arm B) for weeks 26-52, following a 72 hour washout period.	Thrice Weekly FVIII n=3 Participants Subjects will be randomized to receive thrice-weekly FVIII at 40 IU/kg (Arm B) for the first 26 weeks of study. Then, at 26 weeks, they will cross-over to once-weekly FVIII at 40 IU/kg (Arm A) for weeks 26-52, following a 72 hour washout period.
Number of Bleeds	3 bleeds per 26 weeks	16 bleeds per 26 weeks

SECONDARY outcome

Timeframe: The time frame is 52 weeks per subject.

Thrombin generation was performed at week 8 and week 34, i.e. 8 weeks after initiation of factor dosing in Weeks 1-26, and 8 weeks after initiation of factor dosing in Weeks 27-52.

Outcome measures

Measure	Once Weekly FVIII n=3 Participants Subjects will be randomized to receive once-weekly FVIII at 40 IU/kg (Arm A) for the first 26 weeks. Then at 26 weeks, they will cross-over to thrice-weekly FVIII at 40 IU/kg (Arm B) for weeks 26-52, following a 72 hour washout period.	Thrice Weekly FVIII n=3 Participants Subjects will be randomized to receive thrice-weekly FVIII at 40 IU/kg (Arm B) for the first 26 weeks of study. Then, at 26 weeks, they will cross-over to once-weekly FVIII at 40 IU/kg (Arm A) for weeks 26-52, following a 72 hour washout period.
Inter-dose Hypocoagulability by Thrombin Generation	110.65 nMs Interval 99.94 to 249.72	82.86 nMs Interval 65.26 to 157.53

SECONDARY outcome

Timeframe: The time frame is 52 weeks per subject.

F.VIII Activity (IU/mL) performed at week 8 and week 34, i.e. 8 weeks after initiation of factor dosing in Weeks 1-26, and 8 weeks after initiation of factor dosing in Weeks 27-52.

Outcome measures

Measure	Once Weekly FVIII n=3 Participants Subjects will be randomized to receive once-weekly FVIII at 40 IU/kg (Arm A) for the first 26 weeks. Then at 26 weeks, they will cross-over to thrice-weekly FVIII at 40 IU/kg (Arm B) for weeks 26-52, following a 72 hour washout period.	Thrice Weekly FVIII n=3 Participants Subjects will be randomized to receive thrice-weekly FVIII at 40 IU/kg (Arm B) for the first 26 weeks of study. Then, at 26 weeks, they will cross-over to once-weekly FVIII at 40 IU/kg (Arm A) for weeks 26-52, following a 72 hour washout period.
F.VIII Activity	1.04 IU/mL Interval 0.7 to 1.32	0.90 IU/mL Interval 0.87 to 0.94

Adverse Events

Arm A Once-weekly F.VIII at 40 IU/kg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Arm B Thrice-weekly F.VIII at 40 IU/kg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Arm A Once-weekly F.VIII at 40 IU/kg n=4 participants at risk Subjects in Arm A will be randomized to receive either once-weekly F.VIII at 40 IU/kg for the first 26 weeks of study. Then, at 26 weeks, they will undergo "Cross-Over", that is, switch to the alternative Study Arm (thrice-weekly) for the last 26 weeks, following a 72 hour washout period.	Arm B Thrice-weekly F.VIII at 40 IU/kg n=4 participants at risk Subjects will be randomized to receive thrice-weekly F.VIII at 40 IU/kg for the first 26 weeks of study. Then, at 26 weeks, they will undergo "Cross-Over", that is, switch to the alternative Study Arm (once-weekly) for the last 26 weeks, following a 72 hour washout period.
Infections and infestations sinus infection	25.0% 1/4 • Number of events 1 • 52 weeks	0.00% 0/4 • 52 weeks

Additional Information

Margaret V. Ragni, MD, MPH

University of Pittsburgh

Phone: 412-209-7288

Email: ragni@pitt.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place