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BAX 855 PK-guided Dosing (PROPEL)

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ClinicalTrials.gov Identifier: NCT02585960
Recruitment Status : Completed
First Posted : October 26, 2015
Results First Posted : August 26, 2019
Last Update Posted : May 25, 2021
Sponsor:
Collaborator:
Baxalta Innovations GmbH, now part of Shire
Information provided by (Responsible Party):
Takeda ( Baxalta now part of Shire )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Prevention
Condition Hemophilia A
Intervention Biological: PEGylated Recombinant Factor VIII
Enrollment 135
Recruitment Details The study was conducted at 62 study centers in 19 countries between 23 November 2015 (first participant first visit) and 05 August 2018 (last participant last visit).
Pre-assignment Details A total of 135 participants were enrolled in the study. Of them,14 participants were dropped out and did not receive any treatment 121 participants underwent initial pharmacokinetic(PK) assessment with a single administration of BAX 855 and based on their individual PK values, 115 participants were randomized to any one of the prophylactic regimen.
Arm/Group Title BAX 855-Low Level BAX 855-High Level BAX 855-Non-randomized
Hide Arm/Group Description Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 international units per kilogram (IU/kg) intravenous (IV) infusion (PK assessment) followed by a PK-guided dose of BAX 855 twice weekly (Alternating 3 and 4-day infusion intervals or an infusion every 3.5 days), targeting factor VIII (FVIII) trough levels of 1-3%. Depending on participant's individual PK, more frequent dosing was considered if single doses of greater than (>) 80 IU/kg were required or regular FVIII peak levels of 200% were reached. Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 every other day, targeting FVIII trough levels of 8-12%. Depending on participant's individual PK, a different dosing interval was considered to prevent regular high FVIII peak levels. Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) and were not randomized to any treatments.
Period Title: PK/Safety Assessment Period
Started 57 58 6
Completed 1st 6 Month Period 57 53 0
Completed 2nd 6 Month Period 52 48 0
Completed 52 48 0
Not Completed 5 10 6
Reason Not Completed
Physician Decision             0             1             0
Withdrawal by Subject             1             2             5
Non-compliance to study procedures             0             2             0
Other             4             4             0
Withdrawn by sponsor             0             1             0
Screen Failure             0             0             1
Period Title: Prophylactic Treatment Period
Started 52 48 0
Completed 52 43 0
Not Completed 0 5 0
Reason Not Completed
Major protocol deviation             0             4             0
Subject less than 75% exposed to BAX 855             0             1             0
Arm/Group Title BAX 855-Low Level BAX 855-High Level BAX 855-Non-randomized Total
Hide Arm/Group Description Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 twice weekly (Alternating 3 and 4-day infusion intervals or an infusion every 3.5 days), targeting FVIII trough levels of 1-3%. Depending on participant's individual PK, more frequent dosing was considered if single doses of > 80 IU/kg were required or regular FVIII peak levels of 200% were reached. Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 every other day, targeting FVIII trough levels of 8-12%. Depending on participant's individual PK, a different dosing interval was considered to prevent regular high FVIII peak levels. Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) and were not randomized to any treatments. Total of all reporting groups
Overall Number of Baseline Participants 57 58 6 121
Hide Baseline Analysis Population Description
Safety Analysis Set (SAS) included all participants enrolled who had at least one BAX 855 infusion.
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 57 participants 58 participants 6 participants 121 participants
31.1  (13.76) 31.2  (12.22) 25.8  (10.03) 30.9  (12.84)
[1]
Measure Description: Age at the time of informed consent was reported.
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 57 participants 58 participants 6 participants 121 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Male
57
 100.0%
58
 100.0%
6
 100.0%
121
 100.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 57 participants 58 participants 6 participants 121 participants
Hispanic or Latino
2
   3.5%
5
   8.6%
2
  33.3%
9
   7.4%
Not Hispanic or Latino
53
  93.0%
53
  91.4%
4
  66.7%
110
  90.9%
Unknown or Not Reported
2
   3.5%
0
   0.0%
0
   0.0%
2
   1.7%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 57 participants 58 participants 6 participants 121 participants
Asian
14
  24.6%
18
  31.0%
2
  33.3%
34
  28.1%
White
40
  70.2%
36
  62.1%
4
  66.7%
80
  66.1%
Native Latin American
1
   1.8%
1
   1.7%
0
   0.0%
2
   1.7%
Mestizo
0
   0.0%
1
   1.7%
0
   0.0%
1
   0.8%
Other
2
   3.5%
2
   3.4%
0
   0.0%
4
   3.3%
1.Primary Outcome
Title Percentage of Participants With a Total Annualized Bleeding Rate (ABR) of Zero for Second Six Months
Hide Description Annualized bleeding rate was determined by dividing the number of bleeds by observation period in years.
Time Frame Day 183 to Day 364 (6 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included all participants who were randomized to one of the two prophylactic arms and treated prophylactically for any period of time.
Arm/Group Title BAX 855-Low Level BAX 855-High Level
Hide Arm/Group Description:
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 twice weekly (Alternating 3 and 4-day infusion intervals or an infusion every 3.5 days), targeting FVIII trough levels of 1-3%. Depending on participant's individual PK, more frequent dosing was considered if single doses of > 80 IU/kg were required or regular FVIII peak levels of 200% were reached.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 every other day, targeting FVIII trough levels of 8-12%. Depending on participant's individual PK, a different dosing interval was considered to prevent regular high FVIII peak levels.
Overall Number of Participants Analyzed 57 58
Measure Type: Number
Unit of Measure: Percentage of participants
42.1 62.1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BAX 855-Low Level, BAX 855-High Level
Comments The proportion of participants with an ABR of 0 during the second 6-month period on BAX 855 prophylaxis, was compared between the 2 prophylaxis arms using a chi-square test with continuity correction at a 2-sided 5% level of significance.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0545
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Gaussian Statistic estimate
Estimated Value 1.960
Confidence Interval (2-Sided) 95%
-0.038 to 3.958
Estimation Comments Approximately Gaussian Statistic is obtained by taking the square root of the Chi-squared test with continuity adjustment.
2.Secondary Outcome
Title Total Annualized Bleeding Rate for Second Six Months
Hide Description Annualized bleeding rate was determined by dividing the number of bleeds by observation period in years.
Time Frame Day 183 to Day 364 (6 months)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants who were randomized to one of the two prophylactic arms and treated prophylactically for any period of time. Here "Number of participants analyzed" refer to number of participants evaluable for this outcome at specified time point.
Arm/Group Title BAX 855-Low Level BAX 855-High Level
Hide Arm/Group Description:
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 twice weekly (Alternating 3 and 4-day infusion intervals or an infusion every 3.5 days), targeting FVIII trough levels of 1-3%. Depending on participant's individual PK, more frequent dosing was considered if single doses of > 80 IU/kg were required or regular FVIII peak levels of 200% were reached.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 every other day, targeting FVIII trough levels of 8-12%. Depending on participant's individual PK, a different dosing interval was considered to prevent regular high FVIII peak levels.
Overall Number of Participants Analyzed 57 53
Mean (Standard Deviation)
Unit of Measure: Bleeds per year
3.603  (7.512) 1.649  (3.433)
3.Secondary Outcome
Title Annualized Spontaneous Bleeding Rate for Second Six Months
Hide Description Annualized spontaneous bleeding rate was determined by dividing the number of spontaneous bleeds by observation period in years. A bleed was defined as spontaneous if it was not related to injury/trauma.
Time Frame Day 183 to Day 364 (6 months)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants who were randomized to one of the two prophylactic arms and treated prophylactically for any period of time. Here "Number of participants analyzed" refer to number of participants evaluable for this outcome at specified time point.
Arm/Group Title BAX 855 - Low Level BAX 855 - High Level
Hide Arm/Group Description:
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 twice weekly (Alternating 3 and 4-day infusion intervals or an infusion every 3.5 days), targeting FVIII trough levels of 1-3%. Depending on participant's individual PK, more frequent dosing was considered if single doses of > 80 IU/kg were required or regular FVIII peak levels of 200% were reached.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 every other day, targeting FVIII trough levels of 8-12%. Depending on participant's individual PK, a different dosing interval was considered to prevent regular high FVIII peak levels.
Overall Number of Participants Analyzed 57 53
Mean (Standard Deviation)
Unit of Measure: Bleeds per year
2.489  (6.554) 0.737  (1.738)
4.Secondary Outcome
Title Annualized Traumatic Bleeding Rate for Second Six Months
Hide Description Annualized traumatic bleeding rate was determined by dividing the number of traumatic bleeds by observation period in years. A bleed was defined as traumatic if it was related to injury/trauma.
Time Frame Day 183 to Day 364 (6 months)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants who were randomized to one of the two prophylactic arms and treated prophylactically for any period of time. Here "Number of participants analyzed" refer to number of participants evaluable for this outcome at specified time points.
Arm/Group Title BAX 855-Low Level BAX 855-High Level
Hide Arm/Group Description:
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 twice weekly (Alternating 3 and 4-day infusion intervals or an infusion every 3.5 days), targeting FVIII trough levels of 1-3%. Depending on participant's individual PK, more frequent dosing was considered if single doses of > 80 IU/kg were required or regular FVIII peak levels of 200% were reached.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 every other day, targeting FVIII trough levels of 8-12%. Depending on participant's individual PK, a different dosing interval was considered to prevent regular high FVIII peak levels.
Overall Number of Participants Analyzed 57 53
Mean (Standard Deviation)
Unit of Measure: Bleeds per year
1.114  (2.037) 0.912  (2.647)
5.Secondary Outcome
Title Annualized Joint Bleeding Rate (AJBR) for Second Six Months
Hide Description Annualized joint bleeding rate was determined by dividing the number of joint bleeds by observation period in years. An acute joint bleed include some or all of the following: 'aura', pain, swelling, warmth of the skin over the joint, decreased range of motion and difficulty in using the limb compared with baseline or loss of function.
Time Frame Day 183 to Day 364 (6 months)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants who were randomized to one of the two prophylactic arms and treated prophylactically for any period of time. Here "Number of participants analyzed" refer to number of participants evaluable for this outcome at specified time points.
Arm/Group Title BAX 855-Low Level BAX 855-High Level
Hide Arm/Group Description:
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 twice weekly (Alternating 3 and 4-day infusion intervals or an infusion every 3.5 days), targeting FVIII trough levels of 1-3%. Depending on participant's individual PK, more frequent dosing was considered if single doses of > 80 IU/kg were required or regular FVIII peak levels of 200% were reached.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 every other day, targeting FVIII trough levels of 8-12%. Depending on participant's individual PK, a different dosing interval was considered to prevent regular high FVIII peak levels.
Overall Number of Participants Analyzed 57 53
Mean (Standard Deviation)
Unit of Measure: Bleeds per year
2.617  (7.361) 1.079  (2.553)
6.Secondary Outcome
Title Total Weight-adjusted Consumption of BAX 855
Hide Description Total weight-adjusted consumption of BAX 855 were reported.
Time Frame From start of study treatment up to 12 months (completion or termination)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants who were randomized to one of the two prophylactic arms and treated prophylactically for any period of time.
Arm/Group Title BAX 855-Low Level BAX 855-High Level
Hide Arm/Group Description:
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 twice weekly (Alternating 3 and 4-day infusion intervals or an infusion every 3.5 days), targeting FVIII trough levels of 1-3%. Depending on participant's individual PK, more frequent dosing was considered if single doses of > 80 IU/kg were required or regular FVIII peak levels of 200% were reached.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 every other day, targeting FVIII trough levels of 8-12%. Depending on participant's individual PK, a different dosing interval was considered to prevent regular high FVIII peak levels.
Overall Number of Participants Analyzed 57 58
Mean (Standard Deviation)
Unit of Measure: International units per kilogram (IU/kg)
3984.593  (1678.461) 7030.714  (3208.049)
7.Secondary Outcome
Title Number of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Number of Infusions
Hide Description The participant or caregiver rated the overall treatment response using a 4-point efficacy rating scale as Excellent: Full relief of pain and cessation of objective signs of bleeding after a single infusion and no additional infusion is required for the control of bleeding; Good: Definite pain relief and/or improvement in signs of bleeding after a single infusion and possibly requires more than 1 infusion for complete resolution; Fair: Probable and/or slight relief of pain and slight improvement in signs of bleeding after a single infusion and required more than 1 infusion for complete resolution and None: No improvement or condition worsens.
Time Frame 8 hours after study drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants who were randomized to one of the two prophylactic arms and treated prophylactically for any period of time. Here "Number of participants analyzed" refer to number of participants evaluable for this outcome at specified time points.
Arm/Group Title BAX 855-Low Level BAX 855-High Level
Hide Arm/Group Description:
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 twice weekly (Alternating 3 and 4-day infusion intervals or an infusion every 3.5 days), targeting FVIII trough levels of 1-3%. Depending on participant's individual PK, more frequent dosing was considered if single doses of > 80 IU/kg were required or regular FVIII peak levels of 200% were reached.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 every other day, targeting FVIII trough levels of 8-12%. Depending on participant's individual PK, a different dosing interval was considered to prevent regular high FVIII peak levels.
Overall Number of Participants Analyzed 28 19
Overall Number of Units Analyzed
Type of Units Analyzed: Bleeds
97 46
Measure Type: Number
Unit of Measure: Treated Bleeds
Excellent: Bleeds treated with 1 infusion Number Analyzed 58 Bleeds 33 Bleeds
19 17
Excellent: Bleeds treated with 2 infusions Number Analyzed 27 Bleeds 7 Bleeds
3 1
Excellent: Bleeds treated with 3 infusions Number Analyzed 9 Bleeds 3 Bleeds
0 1
Excellent: Bleeds treated with >= 4 infusions Number Analyzed 3 Bleeds 3 Bleeds
0 0
Good: Bleeds treated with 1 infusion Number Analyzed 58 Bleeds 33 Bleeds
36 16
Good: Bleeds treated with 2 infusions Number Analyzed 27 Bleeds 7 Bleeds
16 6
Good: Bleeds treated with 3 infusions Number Analyzed 9 Bleeds 3 Bleeds
5 1
Good: Bleeds treated with >= 4 infusion Number Analyzed 3 Bleeds 3 Bleeds
2 2
Fair: Bleeds treated with 1 infusion Number Analyzed 58 Bleeds 33 Bleeds
2 0
Fair: Bleeds treated with 2 infusions Number Analyzed 27 Bleeds 7 Bleeds
7 0
Fair: Bleeds treated with 3 infusions Number Analyzed 9 Bleeds 3 Bleeds
4 0
Fair: Bleeds treated with >= 4 infusions Number Analyzed 3 Bleeds 3 Bleeds
1 0
None: Bleeds treated with 1 infusion Number Analyzed 58 Bleeds 33 Bleeds
1 0
None: Bleeds treated with 2 infusions Number Analyzed 27 Bleeds 7 Bleeds
1 0
None: Bleeds treated with 3 infusions Number Analyzed 9 Bleeds 3 Bleeds
0 1
None: Bleeds treated with >= 4 infusions Number Analyzed 3 Bleeds 3 Bleeds
0 1
8.Secondary Outcome
Title Number of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Bleed Resolution
Hide Description The participant or caregiver rated the overall treatment response using a 4-point efficacy rating scale as Excellent: Full relief of pain and cessation of objective signs of bleeding after a single infusion and no additional infusion is required for the control of bleeding; Good: Definite pain relief and/or improvement in signs of bleeding after a single infusion and possibly requires more than 1 infusion for complete resolution; Fair: Probable and/or slight relief of pain and slight improvement in signs of bleeding after a single infusion and required more than 1 infusion for complete resolution and None: No improvement or condition worsens.
Time Frame From start of study treatment up to bleed resolution (up to 12 months)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants who were randomized to one of the two prophylactic arms and treated prophylactically for any period of time. Here "Number of participants analyzed" refer to number of participants evaluable for this outcome at specified time points.
Arm/Group Title BAX 855-Low Level BAX 855-High Level
Hide Arm/Group Description:
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 twice weekly (Alternating 3 and 4-day infusion intervals or an infusion every 3.5 days), targeting FVIII trough levels of 1-3%. Depending on participant's individual PK, more frequent dosing was considered if single doses of > 80 IU/kg were required or regular FVIII peak levels of 200% were reached.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 every other day, targeting FVIII trough levels of 8-12%. Depending on participant's individual PK, a different dosing interval was considered to prevent regular high FVIII peak levels.
Overall Number of Participants Analyzed 39 26
Overall Number of Units Analyzed
Type of Units Analyzed: Bleeds
148 78
Measure Type: Number
Unit of Measure: Treated Bleeds
Excellent: Bleeds treated with 1 infusion Number Analyzed 100 Bleeds 58 Bleeds
50 34
Excellent: Bleeds treated with 2 infusions Number Analyzed 29 Bleeds 10 Bleeds
4 2
Good:Bleeds treated with 1 infusion Number Analyzed 100 Bleeds 58 Bleeds
47 24
Good:Bleeds treated with 2 infusions Number Analyzed 29 Bleeds 10 Bleeds
19 7
Good:Bleeds treated with 3 infusions Number Analyzed 13 Bleeds 4 Bleeds
6 3
Good:Bleeds treated with >= 4 infusions Number Analyzed 6 Bleeds 6 Bleeds
3 6
Fair:Bleeds treated with 1 infusion Number Analyzed 100 Bleeds 58 Bleeds
3 0
Fair:Bleeds treated with 2 infusions Number Analyzed 29 Bleeds 10 Bleeds
5 1
Fair:Bleeds treated with 3 infusions Number Analyzed 13 Bleeds 4 Bleeds
7 0
Fair:Bleeds treated with >= 4 infusions Number Analyzed 6 Bleeds 6 Bleeds
3 0
None:Bleeds treated with 2 infusions Number Analyzed 29 Bleeds 10 Bleeds
1 0
None:Bleeds treated with 3 infusions Number Analyzed 13 Bleeds 4 Bleeds
0 1
9.Secondary Outcome
Title Treatment of Bleeding Episodes: Number of BAX 855 Infusions Per Bleeding Episode Required Until Bleed Resolution
Hide Description Infusions of BAX 855 that were required until bleed resolution were reported.
Time Frame From start of study treatment up to 12 months (completion or termination)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants who were randomized to one of the two prophylactic arms and treated prophylactically for any period of time. Here "Number of participants analyzed" refer to number of participants with treated bleeds.
Arm/Group Title BAX 855-Low Level BAX 855-High Level
Hide Arm/Group Description:
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 twice weekly (Alternating 3 and 4-day infusion intervals or an infusion every 3.5 days), targeting FVIII trough levels of 1-3%. Depending on participant's individual PK, more frequent dosing was considered if single doses of > 80 IU/kg were required or regular FVIII peak levels of 200% were reached.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 every other day, targeting FVIII trough levels of 8-12%. Depending on participant's individual PK, a different dosing interval was considered to prevent regular high FVIII peak levels.
Overall Number of Participants Analyzed 41 26
Mean (Standard Deviation)
Unit of Measure: Infusions
1.6  (1.19) 1.6  (1.36)
10.Secondary Outcome
Title Change From Baseline in Hemophilia Joint Health Score (HJHS)- Total Score
Hide Description HJHS was assessed based on the following components of the elbow, knee, and ankle joints: swelling, duration of swelling, muscle atrophy, crepitus on motion, flexion loss, extension loss, joint pain, and strength, together with an assessment of the global gait. The HJHS is a validated 11-item scoring tool based on radiologic and clinical evaluation, sensitive to detect early signs and minor changes. HJHS ranges from 0 to 124. Higher values in the HJHS represent worse situation for the participant.
Time Frame Baseline, Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants who were randomized to one of the two prophylactic arms and treated prophylactically for any period of time. Here "Number of participants analyzed" refer to number of participants evaluable for this outcome at specified time points.
Arm/Group Title BAX 855-Low Level BAX 855-High Level
Hide Arm/Group Description:
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 twice weekly (Alternating 3 and 4-day infusion intervals or an infusion every 3.5 days), targeting FVIII trough levels of 1-3%. Depending on participant's individual PK, more frequent dosing was considered if single doses of > 80 IU/kg were required or regular FVIII peak levels of 200% were reached.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 every other day, targeting FVIII trough levels of 8-12%. Depending on participant's individual PK, a different dosing interval was considered to prevent regular high FVIII peak levels.
Overall Number of Participants Analyzed 57 54
Mean (Standard Deviation)
Unit of Measure: Score on a scale
-1.9  (5.25) -1.1  (7.77)
11.Secondary Outcome
Title Number of Participants With Hemostatic Efficacy Ratings for BAX 855 Treatment of Operative Bleeds
Hide Description The participant or caregiver rated the overall treatment response using a 4-point efficacy rating scale as Excellent: Full relief of pain and cessation of objective signs of bleeding after a single infusion and no additional infusion is required for the control of bleeding; Good: Definite pain relief and/or improvement in signs of bleeding after a single infusion and possibly requires more than 1 infusion for complete resolution; Fair: Probable and/or slight relief of pain and slight improvement in signs of bleeding after a single infusion and required more than 1 infusion for complete resolution and None: No improvement or condition worsens. Hemostatic efficacy was evaluated intra-operatively (from start to end of the procedure), post-operatively (from the end of procedure up to 24 h post procedure), and perioperatively (from the start of procedure to participant discharge from hospital or 14 days after completion of procedure; whichever was first).
Time Frame Day 0 through discharge or 14 days post-surgery
Hide Outcome Measure Data
Hide Analysis Population Description
Surgery analysis set included all participants in the FAS (randomized to one of the two prophylactic arms and treated prophylactically for any period of time) who underwent some form of surgery (including dental) during the course of study participation.
Arm/Group Title BAX 855-Low Level BAX 855-High Level
Hide Arm/Group Description:
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 twice weekly (Alternating 3 and 4-day infusion intervals or an infusion every 3.5 days), targeting FVIII trough levels of 1-3%. Depending on participant's individual PK, more frequent dosing was considered if single doses of > 80 IU/kg were required or regular FVIII peak levels of 200% were reached.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 every other day, targeting FVIII trough levels of 8-12%. Depending on participant's individual PK, a different dosing interval was considered to prevent regular high FVIII peak levels.
Overall Number of Participants Analyzed 3 4
Measure Type: Count of Participants
Unit of Measure: Participants
Excellent: Intra-operative
1
  33.3%
3
  75.0%
Excellent: Post-operative
3
 100.0%
4
 100.0%
Excellent: Peri-operative
2
  66.7%
4
 100.0%
Good: Intra-operative
0
   0.0%
0
   0.0%
Good: Post-operative
0
   0.0%
0
   0.0%
Good: Peri-operative
0
   0.0%
0
   0.0%
Fair: Intra-operative
0
   0.0%
1
  25.0%
Fair: Post-operative
0
   0.0%
0
   0.0%
Fair: Peri-operative
0
   0.0%
0
   0.0%
None: Intra-operative
0
   0.0%
0
   0.0%
None: Post-operative
0
   0.0%
0
   0.0%
None: Peri-operative
0
   0.0%
0
   0.0%
Unknown: Intra-operative
2
  66.7%
0
   0.0%
Unknown: Post-operative
0
   0.0%
0
   0.0%
Unknown: Peri-operative
1
  33.3%
0
   0.0%
12.Secondary Outcome
Title Blood Loss Per Participant in Case of Surgery
Hide Description The intraoperative blood loss was measured by determining the volume of blood and fluid removal through suction into the collection container (waste box and/or cell saver) and the estimated blood loss into swabs and towels during the procedure, per the anesthesiologist's record. Postoperatively, blood loss was determined by the drainage volume collected, which mainly consisted of drainage fluid via vacuum or gravity drain, as applicable. In cases where no drain was present, blood loss was determined by the surgeon's clinical judgment, as applicable or entered as "not available". Blood loss was evaluated intra-operatively (from start to end of the procedure), post-operatively (from the end of procedure up to 24 h post procedure), and perioperatively (from the start of procedure to participant discharge from hospital or 14 days after completion of procedure; whichever was first).
Time Frame Day 0 through discharge or 14 days post-surgery
Hide Outcome Measure Data
Hide Analysis Population Description
Surgery analysis set included all participants in the FAS (randomized to one of the two prophylactic arms and treated prophylactically for any period of time) who underwent some form of surgery (including dental) during the course of study participation.
Arm/Group Title BAX 855-Low Level BAX 855-High Level
Hide Arm/Group Description:
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 twice weekly (Alternating 3 and 4-day infusion intervals or an infusion every 3.5 days), targeting FVIII trough levels of 1-3%. Depending on participant's individual PK, more frequent dosing was considered if single doses of > 80 IU/kg were required or regular FVIII peak levels of 200% were reached.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 every other day, targeting FVIII trough levels of 8-12%. Depending on participant's individual PK, a different dosing interval was considered to prevent regular high FVIII peak levels.
Overall Number of Participants Analyzed 3 4
Mean (Standard Deviation)
Unit of Measure: Milliliters (mL)
Intra-operative: Observed Number Analyzed 3 participants 4 participants
4.400  (4.017) 72.000  (160.741)
Intra-operative: Predicted Average Number Analyzed 3 participants 4 participants
10.600  (9.227) 65.833  (139.290)
Intra-operative: Predicted Maximum Number Analyzed 3 participants 4 participants
20.800  (18.089) 128.333  (231.790)
Post-operative: Observed Number Analyzed 0 participants 1 participants
820.000 [1]   (NA)
Post-operative: Predicted Average Number Analyzed 3 participants 4 participants
10.000  (9.129) 145.000  (320.967)
Post-operative: Predicted Maximum Number Analyzed 3 participants 4 participants
20.200  (17.987) 230.000  (475.563)
[1]
Standard Deviation is not calculated due to a single participant being evaluable.
13.Secondary Outcome
Title Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description An AE was any unfavorable and unintended sign (an abnormal laboratory finding), symptom (rash, pain, discomfort, fever, dizziness, etc.), disease (peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an investigational product (IP), whether or not considered causally related to the IP. A SAE was defined as an untoward medical occurrence that at any dose met one or more of the following criteria: outcome was fatal/results in death, life-threatening, required in-patient hospitalization or resulted in prolongation of an existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event that was not immediately life-threatening or resulted in death or required hospitalization but jeopardize the participant or required medical or surgical intervention to prevent any of the above outcomes.
Time Frame From start of study treatment up to 12 months (completion or termination)
Hide Outcome Measure Data
Hide Analysis Population Description
SAS included all participants enrolled who had at least one BAX 855 infusion.
Arm/Group Title BAX 855-Low Level BAX 855-High Level BAX 855-Non-randomized
Hide Arm/Group Description:
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 international units per kilogram (IU/kg) intravenous (IV) infusion (PK assessment) followed by a PK-guided dose of BAX 855 twice weekly (Alternating 3 and 4-day infusion intervals or an infusion every 3.5 days), targeting FVIII trough levels of 1-3%. Depending on participant's individual PK, more frequent dosing was considered if single doses of >80 IU/kg were required or regular FVIII peak levels of 200% were reached.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 every other day, targeting FVIII trough levels of 8-12%. Depending on participant's individual PK, a different dosing interval was considered to prevent regular high FVIII peak levels.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) and were not randomized to any treatments.
Overall Number of Participants Analyzed 57 58 6
Measure Type: Count of Participants
Unit of Measure: Participants
Number of Participants with SAE
5
   8.8%
5
   8.6%
0
   0.0%
Number of Participants with AE
35
  61.4%
38
  65.5%
0
   0.0%
14.Secondary Outcome
Title Number of Participants With Clinically Significant Changes in Vital Signs Reported as Treatment Related Adverse Events
Hide Description Vital signs included systolic and diastolic blood pressure, pulse rate, respiratory rate, body temperature.
Time Frame From start of study treatment up to 12 months (completion or termination)
Hide Outcome Measure Data
Hide Analysis Population Description
SAS included all participants enrolled who had at least one BAX 855 infusion.
Arm/Group Title BAX 855-Low Level BAX 855-High Level BAX 855-Non-randomized
Hide Arm/Group Description:
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 twice weekly (Alternating 3 and 4-day infusion intervals or an infusion every 3.5 days), targeting FVIII trough levels of 1-3%. Depending on participant's individual PK, more frequent dosing was considered if single doses of > 80 IU/kg were required or regular FVIII peak levels of 200% were reached.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 every other day, targeting FVIII trough levels of 8-12%. Depending on participant's individual PK, a different dosing interval was considered to prevent regular high FVIII peak levels.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) and were not randomized to any treatments.
Overall Number of Participants Analyzed 57 58 6
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
15.Secondary Outcome
Title Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters Reported as Treatment Related Adverse Events
Hide Description Clinical laboratory assessments included clinical chemistry, hematology, lipid panel, genetics, T-cell, B-cell and NK cell (TBNK) and viral serology.
Time Frame From start of study treatment up to 12 months (completion or termination)
Hide Outcome Measure Data
Hide Analysis Population Description
SAS included all participants enrolled who had at least one BAX 855 infusion.
Arm/Group Title BAX 855-Low Level BAX 855-High Level BAX 855-Non-randomized
Hide Arm/Group Description:
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 twice weekly (Alternating 3 and 4-day infusion intervals or an infusion every 3.5 days), targeting FVIII trough levels of 1-3%. Depending on participant's individual PK, more frequent dosing was considered if single doses of > 80 IU/kg were required or regular FVIII peak levels of 200% were reached.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 every other day, targeting FVIII trough levels of 8-12%. Depending on participant's individual PK, a different dosing interval was considered to prevent regular high FVIII peak levels.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) and were not randomized to any treatments.
Overall Number of Participants Analyzed 57 58 6
Measure Type: Count of Participants
Unit of Measure: Participants
2
   3.5%
1
   1.7%
0
   0.0%
16.Secondary Outcome
Title Number of Participants With Positive Inhibitory Antibodies and Binding Antibodies to Factor VIII (FVIII), BAX 855, Polyethylene Glycol (PEG), and Chinese Hamster Ovary (CHO) Protein
Hide Description Positive Inhibitory Antibodies and Binding Antibodies to Factor VIII (FVIII), BAX 855, Polyethylene Glycol (PEG), and Chinese Hamster Ovary (CHO) Protein were reported here.
Time Frame From start of study treatment up to 12 months (completion or termination)
Hide Outcome Measure Data
Hide Analysis Population Description
SAS included all participants enrolled who had at least one BAX 855 infusion.
Arm/Group Title BAX 855-Low Level BAX 855-High Level
Hide Arm/Group Description:
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 international units per kilogram (IU/kg) intravenous (IV) infusion (PK assessment) followed by a PK-guided dose of BAX 855 twice weekly (Alternating 3 and 4-day infusion intervals or an infusion every 3.5 days), targeting FVIII trough levels of 1-3%. Depending on participant's individual PK, more frequent dosing was considered if single doses of >80 IU/kg were required or regular FVIII peak levels of 200% were reached.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 every other day, targeting FVIII trough levels of 8-12%. Depending on participant's individual PK, a different dosing interval was considered to prevent regular high FVIII peak levels.
Overall Number of Participants Analyzed 57 58
Measure Type: Count of Participants
Unit of Measure: Participants
Binding IgG antibodies to FVIII
0
   0.0%
3
   5.2%
Binding IgM antibodies to FVIII
0
   0.0%
0
   0.0%
Binding IgG antibodies to PEG-FVIII
2
   3.5%
7
  12.1%
Binding IgM antibodies to PEG-FVIII
0
   0.0%
1
   1.7%
Binding IgG antibodies to PEG
0
   0.0%
0
   0.0%
Binding IgM antibodies to PEG
1
   1.8%
3
   5.2%
Binding Ig antibodies to CHO
0
   0.0%
0
   0.0%
Inhibitory antibodies to FVIII
0
   0.0%
1
   1.7%
17.Secondary Outcome
Title Change From Baseline in Physical Component Scores (PCS) of the Short Form-36 (SF-36) Health Survey
Hide Description Short Form (36) Health Survey (SF-36) is a 36-item validated, generic health related quality of life (HR QoL) instrument. PCS is a summary scale of the dimensions physical functioning, role physical, bodily pain, and general health. The component score is normalized to a standard population. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both sub-scores and summary scores.
Time Frame Baseline, Month 12 (completion or termination)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants who were randomized to one of the two prophylactic arms and treated prophylactically for any period of time. Here "Number of participants analyzed" refer to number of participants evaluable for this outcome at specified time points.
Arm/Group Title BAX 855-Low Level BAX 855-High Level
Hide Arm/Group Description:
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 international units per kilogram (IU/kg) intravenous (IV) infusion (PK assessment) followed by a PK-guided dose of BAX 855 twice weekly (Alternating 3 and 4-day infusion intervals or an infusion every 3.5 days), targeting FVIII trough levels of 1-3%. Depending on participant's individual PK, more frequent dosing was considered if single doses of >80 IU/kg were required or regular FVIII peak levels of 200% were reached.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 every other day, targeting FVIII trough levels of 8-12%. Depending on participant's individual PK, a different dosing interval was considered to prevent regular high FVIII peak levels.
Overall Number of Participants Analyzed 47 48
Mean (Standard Deviation)
Unit of Measure: Score on a scale
3.551  (8.351) 2.846  (8.658)
18.Secondary Outcome
Title Area Under the Plasma Concentration of BAX 855 From Zero to Infinity (AUC0-inf)
Hide Description Area under the plasma concentration versus time curve from time 0 to infinity of BAX 855 were reported.
Time Frame Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic analysis set (PKAS) included all participants in the SAS that had at least one quantifiable post-dose FVIII activity level without major protocol deviations or events with potential to affect the PK analysis. Here "Number of participants analyzed" refer to number of participants evaluable for this outcome at specified time points.
Arm/Group Title BAX 855-Low Level BAX 855-High Level BAX 855-Non-randomized
Hide Arm/Group Description:
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 international units per kilogram (IU/kg) intravenous (IV) infusion (PK assessment) followed by a PK-guided dose of BAX 855 twice weekly (Alternating 3 and 4-day infusion intervals or an infusion every 3.5 days), targeting FVIII trough levels of 1-3%. Depending on participant's individual PK, more frequent dosing was considered if single doses of >80 IU/kg were required or regular FVIII peak levels of 200% were reached.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 every other day, targeting FVIII trough levels of 8-12%. Depending on participant's individual PK, a different dosing interval was considered to prevent regular high FVIII peak levels.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) and were not randomized to any treatments.
Overall Number of Participants Analyzed 54 57 5
Mean (Standard Deviation)
Unit of Measure: International units*hour per deciliter
2673  (877.3) 2659  (1041) 2214  (355.8)
19.Secondary Outcome
Title Incremental Recovery (IR) at Maximum Plasma Concentration (Cmax) of BAX 855
Hide Description IR at Cmax of BAX 855 were reported.
Time Frame Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion
Hide Outcome Measure Data
Hide Analysis Population Description
PKAS included all participants in the SAS that had at least one quantifiable post-dose FVIII activity level without major protocol deviations or events with potential to affect the PK analysis. Here "Number of participants analyzed" refer to number of participants evaluable for this outcome at specified time points.
Arm/Group Title BAX 855-Low Level BAX 855-High Level BAX 855-Non-randomized
Hide Arm/Group Description:
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 international units per kilogram (IU/kg) intravenous (IV) infusion (PK assessment) followed by a PK-guided dose of BAX 855 twice weekly (Alternating 3 and 4-day infusion intervals or an infusion every 3.5 days), targeting FVIII trough levels of 1-3%. Depending on participant's individual PK, more frequent dosing was considered if single doses of >80 IU/kg were required or regular FVIII peak levels of 200% were reached.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 every other day, targeting FVIII trough levels of 8-12%. Depending on participant's individual PK, a different dosing interval was considered to prevent regular high FVIII peak levels.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) and were not randomized to any treatments.
Overall Number of Participants Analyzed 57 58 5
Mean (Standard Deviation)
Unit of Measure: (IU/dL) / (IU/kg)
2.227  (0.5201) 2.231  (0.5451) 2.478  (0.2016)
20.Secondary Outcome
Title Plasma Half-life (T1/2) of BAX 855
Hide Description T1/2 of BAX 855 in plasma were reported.
Time Frame Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion
Hide Outcome Measure Data
Hide Analysis Population Description
PKAS included all participants in the SAS that had at least one quantifiable post-dose FVIII activity level without major protocol deviations or events with potential to affect the PK analysis.
Arm/Group Title BAX 855-Low Level BAX 855-High Level BAX 855-Non-randomized
Hide Arm/Group Description:
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 international units per kilogram (IU/kg) intravenous (IV) infusion (PK assessment) followed by a PK-guided dose of BAX 855 twice weekly (Alternating 3 and 4-day infusion intervals or an infusion every 3.5 days), targeting FVIII trough levels of 1-3%. Depending on participant's individual PK, more frequent dosing was considered if single doses of >80 IU/kg were required or regular FVIII peak levels of 200% were reached.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 every other day, targeting FVIII trough levels of 8-12%. Depending on participant's individual PK, a different dosing interval was considered to prevent regular high FVIII peak levels.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) and were not randomized to any treatments.
Overall Number of Participants Analyzed 57 58 5
Median (Full Range)
Unit of Measure: hour (h)
15.28
(8.77 to 31.9)
14.66
(6.78 to 35.8)
10.97
(8.67 to 12.5)
21.Secondary Outcome
Title Mean Residence Time (MRT) of BAX 855
Hide Description MRT of BAX 855 were reported.
Time Frame Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic analysis set (PKAS) included all participants in the SAS (participants enrolled who had at least 1 BAX 855 infusion) that had at least one quantifiable post-dose FVIII activity level without major protocol deviations or events with potential to affect the PK analysis.
Arm/Group Title BAX 855-Low Level BAX 855-High Level BAX 855-Non-randomized
Hide Arm/Group Description:
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 international units per kilogram (IU/kg) intravenous (IV) infusion (PK assessment) followed by a PK-guided dose of BAX 855 twice weekly (Alternating 3 and 4-day infusion intervals or an infusion every 3.5 days), targeting FVIII trough levels of 1-3%. Depending on participant's individual PK, more frequent dosing was considered if single doses of >80 IU/kg were required or regular FVIII peak levels of 200% were reached.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 every other day, targeting FVIII trough levels of 8-12%. Depending on participant's individual PK, a different dosing interval was considered to prevent regular high FVIII peak levels.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) and were not randomized to any treatments.
Overall Number of Participants Analyzed 57 58 5
Median (Full Range)
Unit of Measure: hour (h)
22.77
(12.6 to 41.7)
21.50
(10.1 to 52.5)
16.18
(12.6 to 18.2)
22.Secondary Outcome
Title Maximum Plasma Concentration (Cmax) of BAX 855
Hide Description Cmax of BAX 855 were reported.
Time Frame Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion
Hide Outcome Measure Data
Hide Analysis Population Description
PKAS included all participants in the SAS that had at least one quantifiable post-dose FVIII activity level without major protocol deviations or events with potential to affect the PK analysis. Here "Number of participants analyzed" refer to number of participants evaluable for this outcome at specified time points.
Arm/Group Title BAX 855-Low Level BAX 855-High Level BAX 855-Non-randomized
Hide Arm/Group Description:
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 international units per kilogram (IU/kg) intravenous (IV) infusion (PK assessment) followed by a PK-guided dose of BAX 855 twice weekly (Alternating 3 and 4-day infusion intervals or an infusion every 3.5 days), targeting FVIII trough levels of 1-3%. Depending on participant's individual PK, more frequent dosing was considered if single doses of >80 IU/kg were required or regular FVIII peak levels of 200% were reached.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 every other day, targeting FVIII trough levels of 8-12%. Depending on participant's individual PK, a different dosing interval was considered to prevent regular high FVIII peak levels.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) and were not randomized to any treatments.
Overall Number of Participants Analyzed 54 57 5
Mean (Standard Deviation)
Unit of Measure: International units per deciliter(IU/dL)
132.54  (31.83) 135.65  (33.10) 149.18  (12.86)
23.Secondary Outcome
Title Time to Maximum Concentration of BAX 855 in Plasma (Tmax)
Hide Description Tmax of BAX 855 were reported.
Time Frame Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion
Hide Outcome Measure Data
Hide Analysis Population Description
PKAS included all participants in the SAS that had at least one quantifiable post-dose FVIII activity level without major protocol deviations or events with potential to affect the PK analysis.
Arm/Group Title BAX 855-Low Level BAX 855-High Level BAX 855-Non-randomized
Hide Arm/Group Description:
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 international units per kilogram (IU/kg) intravenous (IV) infusion (PK assessment) followed by a PK-guided dose of BAX 855 twice weekly (Alternating 3 and 4-day infusion intervals or an infusion every 3.5 days), targeting FVIII trough levels of 1-3%. Depending on participant's individual PK, more frequent dosing was considered if single doses of >80 IU/kg were required or regular FVIII peak levels of 200% were reached.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 every other day, targeting FVIII trough levels of 8-12%. Depending on participant's individual PK, a different dosing interval was considered to prevent regular high FVIII peak levels.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) and were not randomized to any treatments.
Overall Number of Participants Analyzed 57 58 5
Median (Full Range)
Unit of Measure: hour (h)
0.467
(0.30 to 3.08)
0.475
(0.25 to 3.25)
0.417
(0.38 to 0.53)
24.Secondary Outcome
Title Total Body Clearance (CL) of BAX 855
Hide Description Total body clearance of BAX 855 from blood by the kidney were reported.
Time Frame Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion
Hide Outcome Measure Data
Hide Analysis Population Description
PKAS included all participants in the SAS that had at least one quantifiable post-dose FVIII activity level without major protocol deviations or events with potential to affect the PK analysis.
Arm/Group Title BAX 855-Low Level BAX 855-High Level BAX 855-Non-randomized
Hide Arm/Group Description:
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 international units per kilogram (IU/kg) intravenous (IV) infusion (PK assessment) followed by a PK-guided dose of BAX 855 twice weekly (Alternating 3 and 4-day infusion intervals or an infusion every 3.5 days), targeting FVIII trough levels of 1-3%. Depending on participant's individual PK, more frequent dosing was considered if single doses of >80 IU/kg were required or regular FVIII peak levels of 200% were reached.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 every other day, targeting FVIII trough levels of 8-12%. Depending on participant's individual PK, a different dosing interval was considered to prevent regular high FVIII peak levels.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) and were not randomized to any treatments.
Overall Number of Participants Analyzed 57 58 5
Mean (Standard Deviation)
Unit of Measure: Deciliters per kilogram * hour (dL/kg*h)
0.02477  (0.009580) 0.02624  (0.009333) 0.02774  (0.004385)
25.Secondary Outcome
Title Volume of Distribution at Steady State (Vss)
Hide Description Volume of distribution was defined as the theoretical volume in which the total amount of drug was uniformly distributed to produce the desired blood concentration of a drug. Vss is the apparent volume of distribution at steadystate.
Time Frame Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion
Hide Outcome Measure Data
Hide Analysis Population Description
PKAS included all participants in the SAS that had at least one quantifiable post-dose FVIII activity level without major protocol deviations or events with potential to affect the PK analysis.
Arm/Group Title BAX 855-Low Level BAX 855-High Level BAX 855-Non-randomized
Hide Arm/Group Description:
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 international units per kilogram (IU/kg) intravenous (IV) infusion (PK assessment) followed by a PK-guided dose of BAX 855 twice weekly (Alternating 3 and 4-day infusion intervals or an infusion every 3.5 days), targeting FVIII trough levels of 1-3%. Depending on participant's individual PK, more frequent dosing was considered if single doses of >80 IU/kg were required or regular FVIII peak levels of 200% were reached.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 every other day, targeting FVIII trough levels of 8-12%. Depending on participant's individual PK, a different dosing interval was considered to prevent regular high FVIII peak levels.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) and were not randomized to any treatments.
Overall Number of Participants Analyzed 57 58 5
Mean (Standard Deviation)
Unit of Measure: Deciliters per kilogram (dL/kg)
0.5147  (0.1209) 0.5158  (0.1062) 149.18  (12.86)
26.Secondary Outcome
Title Incremental Recovery (IR) Over Time
Hide Description Incremental recovery was calculated by BAX 855 increment (IU/dL) / BAX 855 dose (IU/kg).
Time Frame Baseline, Month 3, 6, 7.5, 9, 10.5, 12 (Completion or termination)
Hide Outcome Measure Data
Hide Analysis Population Description
PKAS included all participants in the SAS that had at least one quantifiable post-dose FVIII activity level without major protocol deviations or events with potential to affect the PK analysis. Here "Number of participants analyzed" refer to number of participants evaluable for this outcome at specified time points.
Arm/Group Title BAX 855-Low Level BAX 855-High Level
Hide Arm/Group Description:
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 twice weekly (Alternating 3 and 4-day infusion intervals or an infusion every 3.5 days), targeting FVIII trough levels of 1-3%. Depending on participant's individual PK, more frequent dosing was considered if single doses of > 80 IU/kg were required or regular FVIII peak levels of 200% were reached.
Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 every other day, targeting FVIII trough levels of 8-12%. Depending on participant's individual PK, a different dosing interval was considered to prevent regular high FVIII peak levels.
Overall Number of Participants Analyzed 57 58
Mean (Standard Deviation)
Unit of Measure: IU/dL per IU/kg
Baseline Number Analyzed 53 participants 54 participants
2.68  (0.513) 2.70  (0.450)
Month 3 Number Analyzed 56 participants 54 participants
2.68  (0.515) 2.66  (0.459)
Month 6 Number Analyzed 51 participants 49 participants
2.62  (0.585) 2.76  (0.552)
Month 7.5 Number Analyzed 13 participants 11 participants
2.53  (0.360) 2.71  (0.545)
Month 9 Number Analyzed 55 participants 52 participants
2.65  (0.511) 2.68  (0.545)
Month 10.5 Number Analyzed 12 participants 5 participants
2.61  (0.467) 2.58  (0.584)
Completion/ Termination Number Analyzed 56 participants 53 participants
2.71  (0.553) 2.73  (0.689)
Time Frame From start of study treatment up to 12 months (completion or termination)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title BAX 855-Low Level BAX 855-High Level BAX 855-Non-randomized
Hide Arm/Group Description Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 twice weekly (Alternating 3 and 4-day infusion intervals or an infusion every 3.5 days), targeting FVIII trough levels of 1-3%. Depending on participant's individual PK, more frequent dosing was considered if single doses of > 80 IU/kg were required or regular FVIII peak levels of 200% were reached. Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) followed by a PK-guided dose of BAX 855 every other day, targeting FVIII trough levels of 8-12%. Depending on participant's individual PK, a different dosing interval was considered to prevent regular high FVIII peak levels. Participants with severe hemophilia A received a single BAX 855 dose of 60 +/- 5 IU/kg IV infusion (PK assessment) and were not randomized to any treatments.
All-Cause Mortality
BAX 855-Low Level BAX 855-High Level BAX 855-Non-randomized
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/57 (0.00%)      0/58 (0.00%)      0/6 (0.00%)    
Hide Serious Adverse Events
BAX 855-Low Level BAX 855-High Level BAX 855-Non-randomized
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/57 (8.77%)      5/58 (8.62%)      0/6 (0.00%)    
Blood and lymphatic system disorders       
Factor viii inhibition * 1  0/57 (0.00%)  0 1/58 (1.72%)  1 0/6 (0.00%)  0
Infections and infestations       
Abscess limb * 1  1/57 (1.75%)  1 0/58 (0.00%)  0 0/6 (0.00%)  0
Appendicitis * 1  1/57 (1.75%)  1 0/58 (0.00%)  0 0/6 (0.00%)  0
Cellulitis * 1  1/57 (1.75%)  1 0/58 (0.00%)  0 0/6 (0.00%)  0
Injury, poisoning and procedural complications       
Hand fracture * 1  0/57 (0.00%)  0 1/58 (1.72%)  1 0/6 (0.00%)  0
Head injury * 1  1/57 (1.75%)  1 1/58 (1.72%)  1 0/6 (0.00%)  0
Laceration * 1  0/57 (0.00%)  0 1/58 (1.72%)  1 0/6 (0.00%)  0
Multiple injuries * 1  0/57 (0.00%)  0 1/58 (1.72%)  1 0/6 (0.00%)  0
Radius fracture * 1  1/57 (1.75%)  1 0/58 (0.00%)  0 0/6 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Synovitis * 1  1/57 (1.75%)  1 0/58 (0.00%)  0 0/6 (0.00%)  0
Nervous system disorders       
Cerebellar haematoma * 1  0/57 (0.00%)  0 1/58 (1.72%)  1 0/6 (0.00%)  0
1
Term from vocabulary, MedDRA 21.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
BAX 855-Low Level BAX 855-High Level BAX 855-Non-randomized
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   25/57 (43.86%)      25/58 (43.10%)      0/6 (0.00%)    
Gastrointestinal disorders       
Diarrhoea * 1  3/57 (5.26%)  3 2/58 (3.45%)  2 0/6 (0.00%)  0
General disorders       
Pyrexia * 1  2/57 (3.51%)  2 3/58 (5.17%)  3 0/6 (0.00%)  0
Infections and infestations       
Nasopharyngitis * 1  6/57 (10.53%)  8 5/58 (8.62%)  6 0/6 (0.00%)  0
Rhinitis * 1  3/57 (5.26%)  3 3/58 (5.17%)  3 0/6 (0.00%)  0
Sinusitis * 1  3/57 (5.26%)  3 0/58 (0.00%)  0 0/6 (0.00%)  0
Upper respiratory tract infection * 1  6/57 (10.53%)  11 12/58 (20.69%)  16 0/6 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Arthralgia * 1  6/57 (10.53%)  7 5/58 (8.62%)  5 0/6 (0.00%)  0
Back pain * 1  1/57 (1.75%)  2 3/58 (5.17%)  3 0/6 (0.00%)  0
Nervous system disorders       
Headache * 1  5/57 (8.77%)  7 6/58 (10.34%)  7 0/6 (0.00%)  0
1
Term from vocabulary, MedDRA 21.0
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Shire
Phone: +1 866 842 5335
EMail: ClinicalTransparency@shire.com
Layout table for additonal information
Responsible Party: Takeda ( Baxalta now part of Shire )
ClinicalTrials.gov Identifier: NCT02585960    
Other Study ID Numbers: 261303
2014-005477-37 ( EudraCT Number )
First Submitted: October 21, 2015
First Posted: October 26, 2015
Results First Submitted: August 5, 2019
Results First Posted: August 26, 2019
Last Update Posted: May 25, 2021