Trial Outcomes & Findings for A Trial to Compare Prophylaxis Therapy to On-demand Therapy With a New Full Length Recombinant FVIII in Patients With Severe Hemophilia A (NCT NCT01233258)
NCT ID: NCT01233258
Last Updated: 2016-11-28
Results Overview
The annualized number of bleeds experienced by participants
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
80 participants
Primary outcome timeframe
Up to 12 months (6 months per mode of potency assignment according to the randomized cross-over design)
Results posted on
2016-11-28
Participant Flow
Participants were recruited from specialized hemophilia treatment centers.
83 participants were randomized, but 3 of these terminated the study before their first injection of study drug.
Participant milestones
| Measure |
On Demand, BAY 81-8973 Potency First EP Then ADJ
Participants received on-demand treatment with recombinant factor VIII (rFVIII, BAY81-8973) assayed by CS/EP (Chromogenic Substrate Assay per European Pharmacopoeia) for 6 months, followed by cross-over to study drug assayed by CS/ADJ (Chromogenic Substrate Assay/label adjusted to one-stage assay) for 6 months.
|
On Demand, BAY 81-8973 Potency First ADJ Then EP
Participants received on-demand treatment with rFVIII (BAY81-8973) assayed by CS/ADJ for 6 months, followed by cross-over to study drug assayed by CS/EP for 6 months.
|
Low Dose Prophylaxis, BAY 81-8973 Potency First EP Then ADJ
Participants received low dose prophylaxis treatment at 20, 25 or 30 IU/kg twice per week with rFVIII(BAY81-8973) measured by CS/ EP for 6 months then crossed over to study drug measured by CS/ADJ for 6 months.
|
Low Dose Prophylaxis, BAY 81-8973 Potency First ADJ Then EP
Participants received low dose prophylaxis treatment at 20, 25 or 30 IU/kg twice per week with rFVIII (BAY81-8973) measured by CS/ADJ for 6 months then crossed over to study drug measured by CS/ EP for 6 months.
|
High Dose Prophylaxis, BAY 81-8973 Potency First EP Then ADJ
Participants received high dose prophylaxis treatment at 30, 35 or 40 IU/kg 3 times per week with rFVIII (BAY81-8973) measured by CS/ EP for 6 months then crossed over to study drug measured by CS/ADJ for 6 months.
|
High Dose Prophylaxis, BAY 81-8973 Potency First ADJ Then EP
Participants received high dose prophylaxis treatment at 30, 35 or 40 IU/kg 3 times per week with rFVIII(BAY81-8973) measured by CS/ADJ for 6 months then crossed over to study drug measured by CS/ EP for 6 months.
|
|---|---|---|---|---|---|---|
|
First Intervention (6 Months)
STARTED
|
11
|
10
|
14
|
16
|
16
|
16
|
|
First Intervention (6 Months)
Participants Received Treatment
|
11
|
10
|
13
|
15
|
16
|
15
|
|
First Intervention (6 Months)
COMPLETED
|
10
|
10
|
13
|
15
|
16
|
15
|
|
First Intervention (6 Months)
NOT COMPLETED
|
1
|
0
|
1
|
1
|
0
|
1
|
|
Washout (2-3 Days)
STARTED
|
10
|
10
|
13
|
15
|
16
|
15
|
|
Washout (2-3 Days)
COMPLETED
|
10
|
10
|
13
|
15
|
16
|
15
|
|
Washout (2-3 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Second Intervention (6 Months)
STARTED
|
10
|
10
|
13
|
15
|
16
|
15
|
|
Second Intervention (6 Months)
COMPLETED
|
10
|
10
|
13
|
15
|
16
|
15
|
|
Second Intervention (6 Months)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
On Demand, BAY 81-8973 Potency First EP Then ADJ
Participants received on-demand treatment with recombinant factor VIII (rFVIII, BAY81-8973) assayed by CS/EP (Chromogenic Substrate Assay per European Pharmacopoeia) for 6 months, followed by cross-over to study drug assayed by CS/ADJ (Chromogenic Substrate Assay/label adjusted to one-stage assay) for 6 months.
|
On Demand, BAY 81-8973 Potency First ADJ Then EP
Participants received on-demand treatment with rFVIII (BAY81-8973) assayed by CS/ADJ for 6 months, followed by cross-over to study drug assayed by CS/EP for 6 months.
|
Low Dose Prophylaxis, BAY 81-8973 Potency First EP Then ADJ
Participants received low dose prophylaxis treatment at 20, 25 or 30 IU/kg twice per week with rFVIII(BAY81-8973) measured by CS/ EP for 6 months then crossed over to study drug measured by CS/ADJ for 6 months.
|
Low Dose Prophylaxis, BAY 81-8973 Potency First ADJ Then EP
Participants received low dose prophylaxis treatment at 20, 25 or 30 IU/kg twice per week with rFVIII (BAY81-8973) measured by CS/ADJ for 6 months then crossed over to study drug measured by CS/ EP for 6 months.
|
High Dose Prophylaxis, BAY 81-8973 Potency First EP Then ADJ
Participants received high dose prophylaxis treatment at 30, 35 or 40 IU/kg 3 times per week with rFVIII (BAY81-8973) measured by CS/ EP for 6 months then crossed over to study drug measured by CS/ADJ for 6 months.
|
High Dose Prophylaxis, BAY 81-8973 Potency First ADJ Then EP
Participants received high dose prophylaxis treatment at 30, 35 or 40 IU/kg 3 times per week with rFVIII(BAY81-8973) measured by CS/ADJ for 6 months then crossed over to study drug measured by CS/ EP for 6 months.
|
|---|---|---|---|---|---|---|
|
First Intervention (6 Months)
Withdrawal by Subject
|
0
|
0
|
0
|
1
|
0
|
1
|
|
First Intervention (6 Months)
Protocol Violation
|
0
|
0
|
1
|
0
|
0
|
0
|
|
First Intervention (6 Months)
Non-compliance with study medication
|
1
|
0
|
0
|
0
|
0
|
0
|
Baseline Characteristics
A Trial to Compare Prophylaxis Therapy to On-demand Therapy With a New Full Length Recombinant FVIII in Patients With Severe Hemophilia A
Baseline characteristics by cohort
| Measure |
rFVIII (BAY81-8973) on Demand
n=21 Participants
Participants received on-demand treatment with rFVIII (BAY81-8973) assayed by CS/EP (Chromogenic Substrate Assay per European Pharmacopoeia) for 6 months and by CS/ADJ (Chromogenic Substrate Assay/label adjusted to one-stage assay) for 6 months, sequence according to randomization.
|
rFVIII (BAY81-8973) Prophylaxis Low-dose
n=28 Participants
Participants received low dose prophylaxis treatment at 20, 25 or 30 IU/kg twice per week with rFVIII (BAY81-8973) assayed by CS/EP for 6 months and by CS/ADJ for 6 months, sequence according to randomization.
|
rFVIII (BAY81-8973) Prophylaxis High-dose
n=31 Participants
Participants received high dose prophylaxis treatment at 30, 35 or 40 IU/kg 3 times per week with rFVIII (BAY81-8973) assayed by CS/EP for 6 months and by CS/ADJ for 6 months, sequence according to randomization.
|
Total
n=80 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
31.4 years
STANDARD_DEVIATION 10.9 • n=5 Participants
|
28.8 years
STANDARD_DEVIATION 10.9 • n=7 Participants
|
29.1 years
STANDARD_DEVIATION 11.5 • n=5 Participants
|
29.6 years
STANDARD_DEVIATION 11.0 • n=4 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
21 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
80 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Up to 12 months (6 months per mode of potency assignment according to the randomized cross-over design)Population: ITT (Intent to Treat). Low and high dose prophylaxis arms and both potencies combined as planned for the statistical analysis to achieve intended sample size.
The annualized number of bleeds experienced by participants
Outcome measures
| Measure |
rFVIII (BAY81-8973) on Demand
n=21 Participants
Participants received on-demand treatment rFVIII (BAY81-8973) assayed by CS/EP (Chromogenic Substrate Assay per European Pharmacopoeia) for 6 months and by CS/ADJ (Chromogenic Substrate Assay/label adjusted to one-stage assay) for 6 months, sequence according to randomization
|
rFVIII (BAY81-8973) Prophylaxis Treatment
n=59 Participants
Participants received prophylaxis treatment with rFVIII (BAY81-8973) at low-dose (20, 25 or 30 IU/kg twice per week ) and high-dose (30, 35 or 40 IU/kg 3 times per week ) assayed by CS/EP (Chromogenic Substrate Assay per European Pharmacopoeia) for 6 months and by CS/ADJ (Chromogenic Substrate Assay/label adjusted to one-stage assay) for 6 months, sequence according to randomization.
|
rFVIII (BAY81-8973) Prophylaxis High-dose
Participants received prophylaxis treatment with rFVIII (BAY81-8973) at high-dose (30, 35 or 40 IU/kg 3 times per week) assayed by CS/EP (Chromogenic Substrate Assay per European Pharmacopoeia) for 6 months and by CS/ADJ (Chromogenic Substrate Assay/label adjusted to one-stage assay) for 6 months, sequence according to randomization
|
|---|---|---|---|
|
Annualized Number of All Bleeds
|
57.7 Bleeds per year per participant
Standard Deviation 24.6 • Interval 41.7 to 76.3
|
4.9 Bleeds per year per participant
Standard Deviation 6.8 • Interval 0.0 to 7.0
|
—
|
SECONDARY outcome
Timeframe: Up to 6 months (6 months on CS/EP potency assignment)Population: ITT. Low and high dose prophylaxis arms combined as planned for the statistical analysis to achieve sufficient sample size.
The annualized number of bleeds experienced by participants while they were taking rFVIII (BAY81-8973) assayed by CS/EP
Outcome measures
| Measure |
rFVIII (BAY81-8973) on Demand
n=21 Participants
Participants received on-demand treatment rFVIII (BAY81-8973) assayed by CS/EP (Chromogenic Substrate Assay per European Pharmacopoeia) for 6 months and by CS/ADJ (Chromogenic Substrate Assay/label adjusted to one-stage assay) for 6 months, sequence according to randomization
|
rFVIII (BAY81-8973) Prophylaxis Treatment
n=59 Participants
Participants received prophylaxis treatment with rFVIII (BAY81-8973) at low-dose (20, 25 or 30 IU/kg twice per week ) and high-dose (30, 35 or 40 IU/kg 3 times per week ) assayed by CS/EP (Chromogenic Substrate Assay per European Pharmacopoeia) for 6 months and by CS/ADJ (Chromogenic Substrate Assay/label adjusted to one-stage assay) for 6 months, sequence according to randomization.
|
rFVIII (BAY81-8973) Prophylaxis High-dose
Participants received prophylaxis treatment with rFVIII (BAY81-8973) at high-dose (30, 35 or 40 IU/kg 3 times per week) assayed by CS/EP (Chromogenic Substrate Assay per European Pharmacopoeia) for 6 months and by CS/ADJ (Chromogenic Substrate Assay/label adjusted to one-stage assay) for 6 months, sequence according to randomization
|
|---|---|---|---|
|
Annualized Number of All Bleeds During CS/EP Period
|
57.6 Bleeds per year per participant
Standard Deviation 24.3 • Interval 39.4 to 72.7
|
5.1 Bleeds per year per participant
Standard Deviation 8.0 • Interval 0.0 to 6.8
|
—
|
SECONDARY outcome
Timeframe: Up to 6 months (6 months on CS/ADJ potency assignment)Population: ITT. Low and high dose prophylaxis arms combined as planned for the statistical analysis to achieve sufficient sample size.
The annualized number of bleeds experienced by participants while they were taking rFVIII (BAY81-8973) assayed by CS/ADJ
Outcome measures
| Measure |
rFVIII (BAY81-8973) on Demand
n=20 Participants
Participants received on-demand treatment rFVIII (BAY81-8973) assayed by CS/EP (Chromogenic Substrate Assay per European Pharmacopoeia) for 6 months and by CS/ADJ (Chromogenic Substrate Assay/label adjusted to one-stage assay) for 6 months, sequence according to randomization
|
rFVIII (BAY81-8973) Prophylaxis Treatment
n=59 Participants
Participants received prophylaxis treatment with rFVIII (BAY81-8973) at low-dose (20, 25 or 30 IU/kg twice per week ) and high-dose (30, 35 or 40 IU/kg 3 times per week ) assayed by CS/EP (Chromogenic Substrate Assay per European Pharmacopoeia) for 6 months and by CS/ADJ (Chromogenic Substrate Assay/label adjusted to one-stage assay) for 6 months, sequence according to randomization.
|
rFVIII (BAY81-8973) Prophylaxis High-dose
Participants received prophylaxis treatment with rFVIII (BAY81-8973) at high-dose (30, 35 or 40 IU/kg 3 times per week) assayed by CS/EP (Chromogenic Substrate Assay per European Pharmacopoeia) for 6 months and by CS/ADJ (Chromogenic Substrate Assay/label adjusted to one-stage assay) for 6 months, sequence according to randomization
|
|---|---|---|---|
|
Annualized Number of All Bleeds During CS/ADJ Period
|
59.7 Bleeds per year per participant
Standard Deviation 25.1 • Interval 41.0 to 77.8
|
4.8 Bleeds per year per participant
Standard Deviation 6.8 • Interval 0.0 to 7.8
|
—
|
SECONDARY outcome
Timeframe: Up to 12 months (6 months per mode of potency assignment according to the randomized cross-over design)Population: ITT
The percentage of bleeds per participant on on-demand treatment that stopped after two or fewer injections
Outcome measures
| Measure |
rFVIII (BAY81-8973) on Demand
n=21 Participants
Participants received on-demand treatment rFVIII (BAY81-8973) assayed by CS/EP (Chromogenic Substrate Assay per European Pharmacopoeia) for 6 months and by CS/ADJ (Chromogenic Substrate Assay/label adjusted to one-stage assay) for 6 months, sequence according to randomization
|
rFVIII (BAY81-8973) Prophylaxis Treatment
n=20 Participants
Participants received prophylaxis treatment with rFVIII (BAY81-8973) at low-dose (20, 25 or 30 IU/kg twice per week ) and high-dose (30, 35 or 40 IU/kg 3 times per week ) assayed by CS/EP (Chromogenic Substrate Assay per European Pharmacopoeia) for 6 months and by CS/ADJ (Chromogenic Substrate Assay/label adjusted to one-stage assay) for 6 months, sequence according to randomization.
|
rFVIII (BAY81-8973) Prophylaxis High-dose
Participants received prophylaxis treatment with rFVIII (BAY81-8973) at high-dose (30, 35 or 40 IU/kg 3 times per week) assayed by CS/EP (Chromogenic Substrate Assay per European Pharmacopoeia) for 6 months and by CS/ADJ (Chromogenic Substrate Assay/label adjusted to one-stage assay) for 6 months, sequence according to randomization
|
|---|---|---|---|
|
Percentage of Bleeds Per Participant Controlled With ≤ 2 Injections in Participants Treated on Demand With rFVIII (BAY81-8973)
|
96.8 Percentage of bleeds
Interval 77.8 to 100.0
|
100.0 Percentage of bleeds
Interval 65.7 to 100.0
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 monthsPopulation: ITT
The number of bleeds experienced by each participant
Outcome measures
| Measure |
rFVIII (BAY81-8973) on Demand
n=21 Participants
Participants received on-demand treatment rFVIII (BAY81-8973) assayed by CS/EP (Chromogenic Substrate Assay per European Pharmacopoeia) for 6 months and by CS/ADJ (Chromogenic Substrate Assay/label adjusted to one-stage assay) for 6 months, sequence according to randomization
|
rFVIII (BAY81-8973) Prophylaxis Treatment
n=28 Participants
Participants received prophylaxis treatment with rFVIII (BAY81-8973) at low-dose (20, 25 or 30 IU/kg twice per week ) and high-dose (30, 35 or 40 IU/kg 3 times per week ) assayed by CS/EP (Chromogenic Substrate Assay per European Pharmacopoeia) for 6 months and by CS/ADJ (Chromogenic Substrate Assay/label adjusted to one-stage assay) for 6 months, sequence according to randomization.
|
rFVIII (BAY81-8973) Prophylaxis High-dose
n=31 Participants
Participants received prophylaxis treatment with rFVIII (BAY81-8973) at high-dose (30, 35 or 40 IU/kg 3 times per week) assayed by CS/EP (Chromogenic Substrate Assay per European Pharmacopoeia) for 6 months and by CS/ADJ (Chromogenic Substrate Assay/label adjusted to one-stage assay) for 6 months, sequence according to randomization
|
|---|---|---|---|
|
Number of Bleeds During Treatment
|
60.0 Bleeds
Interval 42.0 to 77.0
|
4.0 Bleeds
Interval 0.0 to 8.0
|
2.0 Bleeds
Interval 0.0 to 5.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 3, 6, 9 and 12 months after baselinePopulation: Safety population
A test to ensure that participants have not developed antibodies that will interfere with the action of rFVIII (BAY81-8973)
Outcome measures
| Measure |
rFVIII (BAY81-8973) on Demand
n=21 Participants
Participants received on-demand treatment rFVIII (BAY81-8973) assayed by CS/EP (Chromogenic Substrate Assay per European Pharmacopoeia) for 6 months and by CS/ADJ (Chromogenic Substrate Assay/label adjusted to one-stage assay) for 6 months, sequence according to randomization
|
rFVIII (BAY81-8973) Prophylaxis Treatment
n=28 Participants
Participants received prophylaxis treatment with rFVIII (BAY81-8973) at low-dose (20, 25 or 30 IU/kg twice per week ) and high-dose (30, 35 or 40 IU/kg 3 times per week ) assayed by CS/EP (Chromogenic Substrate Assay per European Pharmacopoeia) for 6 months and by CS/ADJ (Chromogenic Substrate Assay/label adjusted to one-stage assay) for 6 months, sequence according to randomization.
|
rFVIII (BAY81-8973) Prophylaxis High-dose
n=31 Participants
Participants received prophylaxis treatment with rFVIII (BAY81-8973) at high-dose (30, 35 or 40 IU/kg 3 times per week) assayed by CS/EP (Chromogenic Substrate Assay per European Pharmacopoeia) for 6 months and by CS/ADJ (Chromogenic Substrate Assay/label adjusted to one-stage assay) for 6 months, sequence according to randomization
|
|---|---|---|---|
|
Number of Participants With Inhibitory Antibody Formation
3 months after baseline
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Inhibitory Antibody Formation
6 months after baseline
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Inhibitory Antibody Formation
9 months after baseline
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Inhibitory Antibody Formation
12 months after baseline
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
rFVIII (BAY81-8973) Treatment
Serious events: 2 serious events
Other events: 23 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
rFVIII (BAY81-8973) Treatment
n=80 participants at risk
Participants received on-demand or prophylaxis treatment with recombinant factor VIII (rFVIII, BAY81-8973) assayed by CS/EP for 6 months and by CS/ADJ for 6 months, sequence according to randomization
|
|---|---|
|
Injury, poisoning and procedural complications
Head injury
|
1.2%
1/80 • Treatment-emergent adverse event data reported here were collected from start of first treatment up to 12.5 months (end of observation period).
Abbreviations used in the Adverse Events section: Medical Dictionary for Regulatory Activities (MedDRA)
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
1.2%
1/80 • Treatment-emergent adverse event data reported here were collected from start of first treatment up to 12.5 months (end of observation period).
Abbreviations used in the Adverse Events section: Medical Dictionary for Regulatory Activities (MedDRA)
|
Other adverse events
| Measure |
rFVIII (BAY81-8973) Treatment
n=80 participants at risk
Participants received on-demand or prophylaxis treatment with recombinant factor VIII (rFVIII, BAY81-8973) assayed by CS/EP for 6 months and by CS/ADJ for 6 months, sequence according to randomization
|
|---|---|
|
Infections and infestations
Influenza
|
5.0%
4/80 • Treatment-emergent adverse event data reported here were collected from start of first treatment up to 12.5 months (end of observation period).
Abbreviations used in the Adverse Events section: Medical Dictionary for Regulatory Activities (MedDRA)
|
|
Infections and infestations
Nasopharyngitis
|
16.2%
13/80 • Treatment-emergent adverse event data reported here were collected from start of first treatment up to 12.5 months (end of observation period).
Abbreviations used in the Adverse Events section: Medical Dictionary for Regulatory Activities (MedDRA)
|
|
Infections and infestations
Upper respiratory tract infection
|
7.5%
6/80 • Treatment-emergent adverse event data reported here were collected from start of first treatment up to 12.5 months (end of observation period).
Abbreviations used in the Adverse Events section: Medical Dictionary for Regulatory Activities (MedDRA)
|
|
Nervous system disorders
Headache
|
6.2%
5/80 • Treatment-emergent adverse event data reported here were collected from start of first treatment up to 12.5 months (end of observation period).
Abbreviations used in the Adverse Events section: Medical Dictionary for Regulatory Activities (MedDRA)
|
|
Psychiatric disorders
Insomnia
|
5.0%
4/80 • Treatment-emergent adverse event data reported here were collected from start of first treatment up to 12.5 months (end of observation period).
Abbreviations used in the Adverse Events section: Medical Dictionary for Regulatory Activities (MedDRA)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60