Trial Outcomes & Findings for BAY79-4980 Compared to rFVIII-FS in Previously Treated Patients With Severe Hemophilia A (NCT NCT00623727)
NCT ID: NCT00623727
Last Updated: 2013-07-15
Results Overview
Bleeds occurring on the same day were counted as one bleeding event. Bleeds occurring within 72 hours into the same location were also counted as one bleeding event.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
143 participants
Primary outcome timeframe
up to one year
Results posted on
2013-07-15
Participant Flow
Previously treated participants with severe hemophilia A (\<1% FVIII (Factor VIII)), who were currently on on-demand or secondary prophylaxis treatment with any FVIII for ≥150 exposure days (ED) with documented bleeds/injections during the last 6 months prior to study entry could participate in the study.
Of 168 enrolled participants, 25 failed screening.
Participant milestones
| Measure |
rFVIII-FS/Pegylated Liposomes (BAY79-4980)
35 IU/kg body weight of BAY79-4980 1x/week plus 2 dummy injections/week (dummy = rFVIII (recombinant factor VIII)-FS (formulated with sucrose) excipient reconstituted in WFI (sterile water for injection))
|
rFVIII-FS/WFI (BAY14-2222)
25 IU/kg body weight of rFVIII-FS 3x/week (employing 1 percent POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine)-alone liposome (rFVIII-FS-POPC) as blinding agent used for first weekly injection and rFVIII-FS in WFI for 2nd and 3rd injection)
|
|---|---|---|
|
Double Blind (DB)
STARTED
|
70
|
73
|
|
Double Blind (DB)
Participants Received Treatment
|
67
|
72
|
|
Double Blind (DB)
COMPLETED
|
34
|
41
|
|
Double Blind (DB)
NOT COMPLETED
|
36
|
32
|
|
Open Label Follow-up
STARTED
|
0
|
26
|
|
Open Label Follow-up
COMPLETED
|
0
|
18
|
|
Open Label Follow-up
NOT COMPLETED
|
0
|
8
|
|
Open Label Extension Period
STARTED
|
20
|
0
|
|
Open Label Extension Period
COMPLETED
|
20
|
0
|
|
Open Label Extension Period
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
rFVIII-FS/Pegylated Liposomes (BAY79-4980)
35 IU/kg body weight of BAY79-4980 1x/week plus 2 dummy injections/week (dummy = rFVIII (recombinant factor VIII)-FS (formulated with sucrose) excipient reconstituted in WFI (sterile water for injection))
|
rFVIII-FS/WFI (BAY14-2222)
25 IU/kg body weight of rFVIII-FS 3x/week (employing 1 percent POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine)-alone liposome (rFVIII-FS-POPC) as blinding agent used for first weekly injection and rFVIII-FS in WFI for 2nd and 3rd injection)
|
|---|---|---|
|
Double Blind (DB)
Adverse Event
|
1
|
3
|
|
Double Blind (DB)
Physician Decision
|
0
|
1
|
|
Double Blind (DB)
Withdrawal by Subject
|
8
|
2
|
|
Double Blind (DB)
Lack of Efficacy
|
2
|
2
|
|
Double Blind (DB)
Termination of the double-blind period
|
22
|
21
|
|
Double Blind (DB)
Lost to Follow-up
|
1
|
1
|
|
Double Blind (DB)
Protocol Violation
|
2
|
2
|
|
Open Label Follow-up
Withdrawal by Subject
|
0
|
1
|
|
Open Label Follow-up
Study termination
|
0
|
6
|
|
Open Label Follow-up
Participant convenience
|
0
|
1
|
Baseline Characteristics
BAY79-4980 Compared to rFVIII-FS in Previously Treated Patients With Severe Hemophilia A
Baseline characteristics by cohort
| Measure |
rFVIII-FS/Pegylated Liposomes (BAY79-4980)
n=67 Participants
35 IU/kg body weight of BAY79-4980 1x/week plus 2 dummy injections/week (dummy = rFVIII (recombinant factor VIII)-FS (formulated with sucrose) excipient reconstituted in WFI (sterile water for injection))
|
rFVIII-FS/WFI (BAY14-2222)
n=72 Participants
25 IU/kg body weight of rFVIII-FS 3x/week (employing 1 percent POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine)-alone liposome (rFVIII-FS-POPC) as blinding agent used for first weekly injection and rFVIII-FS in WFI for 2nd and 3rd injection)
|
Total
n=139 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
33.0 years
STANDARD_DEVIATION 11.3 • n=99 Participants
|
34.1 years
STANDARD_DEVIATION 13.0 • n=107 Participants
|
33.5 years
STANDARD_DEVIATION 12.2 • n=206 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
67 Participants
n=99 Participants
|
72 Participants
n=107 Participants
|
139 Participants
n=206 Participants
|
|
target joint
Yes
|
54 participants
n=99 Participants
|
56 participants
n=107 Participants
|
110 participants
n=206 Participants
|
|
target joint
No
|
13 participants
n=99 Participants
|
16 participants
n=107 Participants
|
29 participants
n=206 Participants
|
|
Previous treatment
On demand
|
35 participants
n=99 Participants
|
44 participants
n=107 Participants
|
79 participants
n=206 Participants
|
|
Previous treatment
Prophylaxis
|
32 participants
n=99 Participants
|
28 participants
n=107 Participants
|
60 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: up to one yearPopulation: Per protocol (PP) population
Bleeds occurring on the same day were counted as one bleeding event. Bleeds occurring within 72 hours into the same location were also counted as one bleeding event.
Outcome measures
| Measure |
rFVIII-FS/Pegylated Liposomes (BAY79-4980)
n=63 Participants
35 IU/kg body weight of BAY79-4980 1x/week plus 2 dummy injections/week (dummy = rFVIII (recombinant factor VIII)-FS (formulated with sucrose) excipient reconstituted in WFI (sterile water for injection))
|
rFVIII-FS/WFI (BAY14-2222)
n=68 Participants
25 IU/kg body weight of rFVIII-FS 3x/week (employing 1 percent POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine)-alone liposome (rFVIII-FS-POPC) as blinding agent used for first weekly injection and rFVIII-FS in WFI for 2nd and 3rd injection)
|
|---|---|---|
|
Percentage of Participants With Less Than 9 Total Bleeds Per Year
|
38.1 Percentage of participants
|
72.1 Percentage of participants
|
SECONDARY outcome
Timeframe: up to one yearPopulation: PP population
Bleeds occurring on the same day were counted as one bleeding event. Bleeds occurring within 72 hours into the same location were also counted as one bleeding event.
Outcome measures
| Measure |
rFVIII-FS/Pegylated Liposomes (BAY79-4980)
n=63 Participants
35 IU/kg body weight of BAY79-4980 1x/week plus 2 dummy injections/week (dummy = rFVIII (recombinant factor VIII)-FS (formulated with sucrose) excipient reconstituted in WFI (sterile water for injection))
|
rFVIII-FS/WFI (BAY14-2222)
n=68 Participants
25 IU/kg body weight of rFVIII-FS 3x/week (employing 1 percent POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine)-alone liposome (rFVIII-FS-POPC) as blinding agent used for first weekly injection and rFVIII-FS in WFI for 2nd and 3rd injection)
|
|---|---|---|
|
Percentage of Participants With Less Than 5 Joint Bleeds Per Year
|
38.1 Percentage of participants
|
63.2 Percentage of participants
|
SECONDARY outcome
Timeframe: up to one yearPopulation: PP population in responders
Bleeds occurring on the same day were counted as one bleeding event. Bleeds occurring within 72 hours into the same location were also counted as one bleeding event. Responders were the subjects with less than 9 total bleeds per year
Outcome measures
| Measure |
rFVIII-FS/Pegylated Liposomes (BAY79-4980)
n=24 Participants
35 IU/kg body weight of BAY79-4980 1x/week plus 2 dummy injections/week (dummy = rFVIII (recombinant factor VIII)-FS (formulated with sucrose) excipient reconstituted in WFI (sterile water for injection))
|
rFVIII-FS/WFI (BAY14-2222)
n=49 Participants
25 IU/kg body weight of rFVIII-FS 3x/week (employing 1 percent POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine)-alone liposome (rFVIII-FS-POPC) as blinding agent used for first weekly injection and rFVIII-FS in WFI for 2nd and 3rd injection)
|
|---|---|---|
|
Number of Joint Bleeds Per Participant Per Year in Responders
|
2.341 Joint bleeds per year
Interval 0.0 to 8.91
|
0.000 Joint bleeds per year
Interval 0.0 to 7.59
|
OTHER_PRE_SPECIFIED outcome
Timeframe: up to one yearPopulation: PP population
Bleeds occurring on the same day were counted as one bleeding event. Bleeds occurring within 72 hours into the same location were also counted as one bleeding event. Number of bleeds 3 weeks after the first infusion per 12 months
Outcome measures
| Measure |
rFVIII-FS/Pegylated Liposomes (BAY79-4980)
n=63 Participants
35 IU/kg body weight of BAY79-4980 1x/week plus 2 dummy injections/week (dummy = rFVIII (recombinant factor VIII)-FS (formulated with sucrose) excipient reconstituted in WFI (sterile water for injection))
|
rFVIII-FS/WFI (BAY14-2222)
n=68 Participants
25 IU/kg body weight of rFVIII-FS 3x/week (employing 1 percent POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine)-alone liposome (rFVIII-FS-POPC) as blinding agent used for first weekly injection and rFVIII-FS in WFI for 2nd and 3rd injection)
|
|---|---|---|
|
Number of Bleeds Per Year
|
9.96 bleeds per year
Interval 0.0 to 72.2
|
2.20 bleeds per year
Interval 0.0 to 22.8
|
OTHER_PRE_SPECIFIED outcome
Timeframe: up to one yearPopulation: PP Population
Bleeds occurring on the same day were counted as one bleeding event. Bleeds occurring within 72 hours into the same location were also counted as one bleeding event.
Outcome measures
| Measure |
rFVIII-FS/Pegylated Liposomes (BAY79-4980)
n=63 Participants
35 IU/kg body weight of BAY79-4980 1x/week plus 2 dummy injections/week (dummy = rFVIII (recombinant factor VIII)-FS (formulated with sucrose) excipient reconstituted in WFI (sterile water for injection))
|
rFVIII-FS/WFI (BAY14-2222)
n=68 Participants
25 IU/kg body weight of rFVIII-FS 3x/week (employing 1 percent POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine)-alone liposome (rFVIII-FS-POPC) as blinding agent used for first weekly injection and rFVIII-FS in WFI for 2nd and 3rd injection)
|
|---|---|---|
|
Percentage of Bleeds Treated by Various Numbers of Injections
>3 injections
|
5.0 percentage of bleeds
|
4.7 percentage of bleeds
|
|
Percentage of Bleeds Treated by Various Numbers of Injections
1-2 injections
|
88.5 percentage of bleeds
|
93.0 percentage of bleeds
|
|
Percentage of Bleeds Treated by Various Numbers of Injections
1 injection
|
73.2 percentage of bleeds
|
81.7 percentage of bleeds
|
|
Percentage of Bleeds Treated by Various Numbers of Injections
2 injections
|
15.3 percentage of bleeds
|
11.3 percentage of bleeds
|
|
Percentage of Bleeds Treated by Various Numbers of Injections
3 injections
|
6.5 percentage of bleeds
|
2.3 percentage of bleeds
|
OTHER_PRE_SPECIFIED outcome
Timeframe: up to one yearPopulation: ITT population
Total number of units per kg of study medication (rFVIII) administered to participant for one year. rFVIII is recombinant factor VIII, factor VIII is functional coagulation factor
Outcome measures
| Measure |
rFVIII-FS/Pegylated Liposomes (BAY79-4980)
n=67 Participants
35 IU/kg body weight of BAY79-4980 1x/week plus 2 dummy injections/week (dummy = rFVIII (recombinant factor VIII)-FS (formulated with sucrose) excipient reconstituted in WFI (sterile water for injection))
|
rFVIII-FS/WFI (BAY14-2222)
n=72 Participants
25 IU/kg body weight of rFVIII-FS 3x/week (employing 1 percent POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine)-alone liposome (rFVIII-FS-POPC) as blinding agent used for first weekly injection and rFVIII-FS in WFI for 2nd and 3rd injection)
|
|---|---|---|
|
Total rFVIII Consumption Per Year
|
2524 IU per kg
Interval 1580.0 to 11788.0
|
4378 IU per kg
Interval 3701.0 to 12789.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 6 months after start of open label extension periodPopulation: Participants who completed open label extension period
Bleeds occurring on the same day were counted as one bleeding event. Bleeds occurring within 72 hours into the same location were also counted as one bleeding event.
Outcome measures
| Measure |
rFVIII-FS/Pegylated Liposomes (BAY79-4980)
n=20 Participants
35 IU/kg body weight of BAY79-4980 1x/week plus 2 dummy injections/week (dummy = rFVIII (recombinant factor VIII)-FS (formulated with sucrose) excipient reconstituted in WFI (sterile water for injection))
|
rFVIII-FS/WFI (BAY14-2222)
25 IU/kg body weight of rFVIII-FS 3x/week (employing 1 percent POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine)-alone liposome (rFVIII-FS-POPC) as blinding agent used for first weekly injection and rFVIII-FS in WFI for 2nd and 3rd injection)
|
|---|---|---|
|
Percentage of Participants With Less Than 9 Total Bleeds Per Year in the Open Label Extension Period
|
55.0 Percentage of participants
|
—
|
Adverse Events
rFVIII-FS/Pegylated Liposomes (BAY79-4980) - Double Blind
Serious events: 7 serious events
Other events: 27 other events
Deaths: 0 deaths
rFVIII-FS/WFI (BAY14-2222) - Double Blind
Serious events: 1 serious events
Other events: 27 other events
Deaths: 0 deaths
rFVIII-FS/WFI (BAY14-2222) - Follow-up
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
rFVIII-FS/Pegylated Liposomes (BAY79-4980) - Extension
Serious events: 1 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
rFVIII-FS/Pegylated Liposomes (BAY79-4980) - Double Blind
n=67 participants at risk
Reporting Group 1 (RG1): Double Blind Study, 35 IU/kg body weight of BAY79-4980 1x/week plus 2 dummy injections/week (dummy = rFVIII-FS excipient reconstituted in WFI)
|
rFVIII-FS/WFI (BAY14-2222) - Double Blind
n=72 participants at risk
Reporting group 2 (RG2): Double Blind Study, 25 IU/kg body weight of rFVIII-FS 3x/week (employing 1 percent POPC-alone liposome (rFVIII-FS-POPC) as blinding agent used for first weekly injection and rFVIII-FS in WFI for 2nd and 3rd injection)
|
rFVIII-FS/WFI (BAY14-2222) - Follow-up
n=26 participants at risk
Reporting group 3 (RG3): Open Label Follow-up, 25 IU/kg body weight of rFVIII-FS 3x/week (employing 1 percent POPC-alone liposome (rFVIII-FS-POPC) as blinding agent used for first weekly injection and rFVIII-FS in WFI for 2nd and 3rd injection)
|
rFVIII-FS/Pegylated Liposomes (BAY79-4980) - Extension
n=20 participants at risk
Reporting group 4 (RG4): Open Label Extension, 35 IU/kg body weight of BAY79-4980 1x/week plus 2 dummy injections/week (dummy = rFVIII-FS excipient reconstituted in WFI)
|
|---|---|---|---|---|
|
Eye disorders
Glaucoma
|
1.5%
1/67
|
0.00%
0/72
|
0.00%
0/26
|
0.00%
0/20
|
|
Gastrointestinal disorders
Melaena
|
1.5%
1/67
|
0.00%
0/72
|
0.00%
0/26
|
0.00%
0/20
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
1.5%
1/67
|
0.00%
0/72
|
0.00%
0/26
|
0.00%
0/20
|
|
General disorders
Oedema
|
1.5%
1/67
|
0.00%
0/72
|
0.00%
0/26
|
0.00%
0/20
|
|
Immune system disorders
Hypersensitivity
|
1.5%
1/67
|
0.00%
0/72
|
0.00%
0/26
|
0.00%
0/20
|
|
Infections and infestations
Device related infection
|
0.00%
0/67
|
1.4%
1/72
|
0.00%
0/26
|
0.00%
0/20
|
|
Infections and infestations
Tinea pedis
|
1.5%
1/67
|
0.00%
0/72
|
0.00%
0/26
|
0.00%
0/20
|
|
Infections and infestations
Varicella
|
0.00%
0/67
|
0.00%
0/72
|
0.00%
0/26
|
5.0%
1/20
|
|
Metabolism and nutrition disorders
Abnormal weight gain
|
1.5%
1/67
|
0.00%
0/72
|
0.00%
0/26
|
0.00%
0/20
|
|
Musculoskeletal and connective tissue disorders
Compartment syndrome
|
1.5%
1/67
|
0.00%
0/72
|
0.00%
0/26
|
0.00%
0/20
|
|
Psychiatric disorders
Anxiety
|
1.5%
1/67
|
0.00%
0/72
|
0.00%
0/26
|
0.00%
0/20
|
|
Renal and urinary disorders
Urinary retention
|
1.5%
1/67
|
0.00%
0/72
|
0.00%
0/26
|
0.00%
0/20
|
Other adverse events
| Measure |
rFVIII-FS/Pegylated Liposomes (BAY79-4980) - Double Blind
n=67 participants at risk
Reporting Group 1 (RG1): Double Blind Study, 35 IU/kg body weight of BAY79-4980 1x/week plus 2 dummy injections/week (dummy = rFVIII-FS excipient reconstituted in WFI)
|
rFVIII-FS/WFI (BAY14-2222) - Double Blind
n=72 participants at risk
Reporting group 2 (RG2): Double Blind Study, 25 IU/kg body weight of rFVIII-FS 3x/week (employing 1 percent POPC-alone liposome (rFVIII-FS-POPC) as blinding agent used for first weekly injection and rFVIII-FS in WFI for 2nd and 3rd injection)
|
rFVIII-FS/WFI (BAY14-2222) - Follow-up
n=26 participants at risk
Reporting group 3 (RG3): Open Label Follow-up, 25 IU/kg body weight of rFVIII-FS 3x/week (employing 1 percent POPC-alone liposome (rFVIII-FS-POPC) as blinding agent used for first weekly injection and rFVIII-FS in WFI for 2nd and 3rd injection)
|
rFVIII-FS/Pegylated Liposomes (BAY79-4980) - Extension
n=20 participants at risk
Reporting group 4 (RG4): Open Label Extension, 35 IU/kg body weight of BAY79-4980 1x/week plus 2 dummy injections/week (dummy = rFVIII-FS excipient reconstituted in WFI)
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.00%
0/67
|
2.8%
2/72
|
0.00%
0/26
|
10.0%
2/20
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/67
|
0.00%
0/72
|
0.00%
0/26
|
5.0%
1/20
|
|
Gastrointestinal disorders
Nausea
|
6.0%
4/67
|
2.8%
2/72
|
0.00%
0/26
|
0.00%
0/20
|
|
General disorders
Pyrexia
|
4.5%
3/67
|
4.2%
3/72
|
3.8%
1/26
|
5.0%
1/20
|
|
Infections and infestations
Influenza
|
7.5%
5/67
|
2.8%
2/72
|
0.00%
0/26
|
0.00%
0/20
|
|
Infections and infestations
Localised infection
|
0.00%
0/67
|
0.00%
0/72
|
0.00%
0/26
|
5.0%
1/20
|
|
Infections and infestations
Nasopharyngitis
|
14.9%
10/67
|
16.7%
12/72
|
0.00%
0/26
|
30.0%
6/20
|
|
Infections and infestations
Varicella
|
0.00%
0/67
|
0.00%
0/72
|
0.00%
0/26
|
5.0%
1/20
|
|
Injury, poisoning and procedural complications
Limb injury
|
0.00%
0/67
|
0.00%
0/72
|
0.00%
0/26
|
10.0%
2/20
|
|
Investigations
Blood amylase increased
|
1.5%
1/67
|
1.4%
1/72
|
0.00%
0/26
|
5.0%
1/20
|
|
Investigations
Lipase increased
|
1.5%
1/67
|
1.4%
1/72
|
0.00%
0/26
|
5.0%
1/20
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
10.4%
7/67
|
6.9%
5/72
|
3.8%
1/26
|
0.00%
0/20
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.0%
4/67
|
2.8%
2/72
|
0.00%
0/26
|
5.0%
1/20
|
|
Musculoskeletal and connective tissue disorders
Haemophilic arthropathy
|
0.00%
0/67
|
0.00%
0/72
|
0.00%
0/26
|
5.0%
1/20
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/67
|
0.00%
0/72
|
0.00%
0/26
|
5.0%
1/20
|
|
Nervous system disorders
Headache
|
9.0%
6/67
|
11.1%
8/72
|
0.00%
0/26
|
5.0%
1/20
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/67
|
0.00%
0/72
|
0.00%
0/26
|
5.0%
1/20
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/67
|
0.00%
0/72
|
0.00%
0/26
|
10.0%
2/20
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
6.0%
4/67
|
5.6%
4/72
|
0.00%
0/26
|
0.00%
0/20
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
0.00%
0/67
|
0.00%
0/72
|
0.00%
0/26
|
5.0%
1/20
|
|
Skin and subcutaneous tissue disorders
Rash
|
4.5%
3/67
|
5.6%
4/72
|
0.00%
0/26
|
0.00%
0/20
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Bayer will have up to 30/45 days to review publications, and may request an additional publication delay of up to 60 days to allow for filing a Patent Application (if applicable). No publication of single center data should be done prior of publication if multi -center data.
- Publication restrictions are in place
Restriction type: OTHER