Trial Outcomes & Findings for BAX 855 Pediatric Study (NCT NCT02210091)
NCT ID: NCT02210091
Last Updated: 2021-05-24
Results Overview
Inhibitory antibodies to FVIII were measured using the Nijmegen modification of the Bethesda assay. Incidence of an FVIII inhibitory antibody was defined as an inhibitor level ≥0.6 Bethesda units \[BU\].
COMPLETED
PHASE3
75 participants
After first exposure to BAX 855 until completion of study - approx. 6 months per participant.
2021-05-24
Participant Flow
52 sites participated in this study. 39 study sites enrolled participants and 13 sites were initiated but were inactive.
73 participants enrolled and were screened for study participation. There were 9 screen failures. Among these, 2 participants were screen failures at first screening but entered the study later. 66 participants were dosed in the prophylactic part of the study, of whom 31 participants were also dosed in the PK part prior to prophylaxis.
Participant milestones
| Measure |
<6 Years Old
|
6 to <12 Years Old
|
|---|---|---|
|
Overall Study
STARTED
|
32
|
34
|
|
Overall Study
COMPLETED
|
32
|
32
|
|
Overall Study
NOT COMPLETED
|
0
|
2
|
Reasons for withdrawal
| Measure |
<6 Years Old
|
6 to <12 Years Old
|
|---|---|---|
|
Overall Study
Physician Decision
|
0
|
1
|
|
Overall Study
Withdrawal by Sponsor
|
0
|
1
|
Baseline Characteristics
BAX 855 Pediatric Study
Baseline characteristics by cohort
| Measure |
<6 Years Old
n=32 Participants
|
6 to <12 Years Old
n=34 Participants
|
Total
n=66 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
3.7 Years
STANDARD_DEVIATION 1.17 • n=5 Participants
|
8.1 Years
STANDARD_DEVIATION 1.92 • n=7 Participants
|
6.0 Years
STANDARD_DEVIATION 2.70 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
32 Participants
n=5 Participants
|
33 Participants
n=7 Participants
|
65 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: After first exposure to BAX 855 until completion of study - approx. 6 months per participant.Population: Participants in the BAX 855 Safety Analysis Set who developed an inhibitor at any time plus participants who did not develop an inhibitor, had 50 or more exposure days (EDs) to BAX 855 and had FVIII Inhibitory test results after 50 EDs.
Inhibitory antibodies to FVIII were measured using the Nijmegen modification of the Bethesda assay. Incidence of an FVIII inhibitory antibody was defined as an inhibitor level ≥0.6 Bethesda units \[BU\].
Outcome measures
| Measure |
<6 Years Old
n=29 Participants
Participants \< 6 years old who received at least one dose of BAX 855.
|
6 to <12 Years Old
n=28 Participants
Participants 6 to \<12 years old who received at least one dose of BAX 855.
|
BAX 855 Safety Analysis Set
n=57 Participants
Participants who received at least one dose of BAX 855.
|
|---|---|---|---|
|
Number of Participants With Inhibitory Antibodies to Factor VIII (FVIII)
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs lastPopulation: Full Analysis Set: All participants who received at least 1 dose of BAX 855 in either PK or prophylaxis part of study
The annualized bleeding rate (ABR) during the prophylaxis period was assessed based upon each individual bleeding episode, spontaneous or traumatic, recorded in the participant´s diary and/or recorded in the physician/nurse/study site notes. The annualized bleeding rate was analyzed using a generalized linear model framework assuming a negative binomial distribution with a logarithmic link function and presence or absence of target joints and age cohort as covariates and duration of the observation period in years as offset. Point estimates for the mean and 95% confidence intervals are presented.
Outcome measures
| Measure |
<6 Years Old
n=32 Participants
Participants \< 6 years old who received at least one dose of BAX 855.
|
6 to <12 Years Old
n=34 Participants
Participants 6 to \<12 years old who received at least one dose of BAX 855.
|
BAX 855 Safety Analysis Set
n=66 Participants
Participants who received at least one dose of BAX 855.
|
|---|---|---|---|
|
Annualized Bleeding Rate (ABR)
Overall annualized bleeding rate
|
2.37 bleeding episodes per year
95% Confidence Interval 3.508 • Interval 1.486 to 3.778
|
3.75 bleeding episodes per year
95% Confidence Interval 9.046 • Interval 2.429 to 5.781
|
3.04 bleeding episodes per year
95% Confidence Interval 6.988 • Interval 2.208 to 4.186
|
|
Annualized Bleeding Rate (ABR)
Annualized rate of joint bleeds
|
0.862 bleeding episodes per year
95% Confidence Interval 2.622 • Interval 0.381 to 1.946
|
1.355 bleeding episodes per year
95% Confidence Interval 2.590 • Interval 0.648 to 2.833
|
1.103 bleeding episodes per year
95% Confidence Interval 2.597 • Interval 0.637 to 1.91
|
|
Annualized Bleeding Rate (ABR)
Annualized rate of target joint bleeds
|
0 bleeding episodes per year
95% Confidence Interval 0.354 • Interval 0.0 to
NA = infinity
|
0 bleeding episodes per year
95% Confidence Interval 1.146 • Interval 0.0 to
NA = infinity
|
0 bleeding episodes per year
95% Confidence Interval 0.865 • Interval 0.0 to
NA = infinity
|
|
Annualized Bleeding Rate (ABR)
Annualized rate of non-target joint bleeds
|
0.763 bleeding episodes per year
95% Confidence Interval 2.618 • Interval 0.299 to 1.95
|
0.998 bleeding episodes per year
95% Confidence Interval 2.253 • Interval 0.41 to 2.43
|
0.892 bleeding episodes per year
95% Confidence Interval 2.420 • Interval 0.466 to 1.706
|
|
Annualized Bleeding Rate (ABR)
Annualized spontaneous bleeding rate
|
1.018 bleeding episodes per year
95% Confidence Interval 2.048 • Interval 0.523 to 1.978
|
1.316 bleeding episodes per year
95% Confidence Interval 2.467 • Interval 0.71 to 2.438
|
1.164 bleeding episodes per year
95% Confidence Interval 2.260 • Interval 0.74 to 1.832
|
|
Annualized Bleeding Rate (ABR)
Annualized rate of injury-related bleeds
|
1.628 bleeding episodes per year
95% Confidence Interval 2.308 • Interval 0.989 to 2.679
|
2.586 bleeding episodes per year
95% Confidence Interval 8.678 • Interval 1.639 to 4.08
|
2.089 bleeding episodes per year
95% Confidence Interval 6.471 • Interval 1.492 to 2.925
|
SECONDARY outcome
Timeframe: During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs lastPopulation: BAX 855 Safety Analysis Set.
Outcome measures
| Measure |
<6 Years Old
n=32 Participants
Participants \< 6 years old who received at least one dose of BAX 855.
|
6 to <12 Years Old
n=34 Participants
Participants 6 to \<12 years old who received at least one dose of BAX 855.
|
BAX 855 Safety Analysis Set
n=66 Participants
Participants who received at least one dose of BAX 855.
|
|---|---|---|---|
|
Consumption of BAX 855: Number of Prophylactic Infusions Per Month Per Participant
|
8.07 infusions per month
Standard Deviation 0.245
|
7.72 infusions per month
Standard Deviation 0.974
|
7.89 infusions per month
Standard Deviation 0.736
|
SECONDARY outcome
Timeframe: During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs lastPopulation: BAX 855 Safety Analysis Set.
Outcome measures
| Measure |
<6 Years Old
n=32 Participants
Participants \< 6 years old who received at least one dose of BAX 855.
|
6 to <12 Years Old
n=34 Participants
Participants 6 to \<12 years old who received at least one dose of BAX 855.
|
BAX 855 Safety Analysis Set
n=66 Participants
Participants who received at least one dose of BAX 855.
|
|---|---|---|---|
|
Consumption of BAX 855: Number of Prophylactic Infusions Per Year (Annualized) Per Participant
|
96.82 infusions per year
Standard Deviation 2.942
|
92.61 infusions per year
Standard Deviation 11.693
|
94.65 infusions per year
Standard Deviation 8.834
|
SECONDARY outcome
Timeframe: During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs lastPopulation: BAX 855 Safety Analysis Set.
Outcome measures
| Measure |
<6 Years Old
n=32 Participants
Participants \< 6 years old who received at least one dose of BAX 855.
|
6 to <12 Years Old
n=34 Participants
Participants 6 to \<12 years old who received at least one dose of BAX 855.
|
BAX 855 Safety Analysis Set
n=66 Participants
Participants who received at least one dose of BAX 855.
|
|---|---|---|---|
|
Consumption of BAX 855: Weight-adjusted Dose of Prophylactic Infusions Per Month Per Participant
|
458.93 IU/kg
Standard Deviation 46.161
|
455.86 IU/kg
Standard Deviation 76.101
|
457.35 IU/kg
Standard Deviation 62.919
|
SECONDARY outcome
Timeframe: During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs lastPopulation: BAX 855 Safety Analysis Set.
Outcome measures
| Measure |
<6 Years Old
n=32 Participants
Participants \< 6 years old who received at least one dose of BAX 855.
|
6 to <12 Years Old
n=34 Participants
Participants 6 to \<12 years old who received at least one dose of BAX 855.
|
BAX 855 Safety Analysis Set
n=66 Participants
Participants who received at least one dose of BAX 855.
|
|---|---|---|---|
|
Consumption of BAX 855: Weight-adjusted Dose of Prophylactic Infusions Per Year (Annualized) Per Participant
|
5507.20 IU/kg
Standard Deviation 553.931
|
5470.32 IU/kg
Standard Deviation 913.210
|
5488.20 IU/kg
Standard Deviation 755.033
|
SECONDARY outcome
Timeframe: During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs lastPopulation: Participants in the BAX 855 Safety Analysis Set who had treated bleeding episodes.
Outcome measures
| Measure |
<6 Years Old
n=15 Participants
Participants \< 6 years old who received at least one dose of BAX 855.
|
6 to <12 Years Old
n=19 Participants
Participants 6 to \<12 years old who received at least one dose of BAX 855.
|
BAX 855 Safety Analysis Set
n=34 Participants
Participants who received at least one dose of BAX 855.
|
|---|---|---|---|
|
Consumption of BAX 855: Number of Infusions Per Bleeding Episode
|
1.17 infusions
Standard Deviation 0.362
|
1.40 infusions
Standard Deviation 0.655
|
1.30 infusions
Standard Deviation 0.551
|
SECONDARY outcome
Timeframe: During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs lastPopulation: Participants in the BAX 855 Safety Analysis Set who had treated bleeding episodes.
Outcome measures
| Measure |
<6 Years Old
n=25 bleeding episodes
Participants \< 6 years old who received at least one dose of BAX 855.
|
6 to <12 Years Old
n=45 bleeding episodes
Participants 6 to \<12 years old who received at least one dose of BAX 855.
|
BAX 855 Safety Analysis Set
n=70 bleeding episodes
Participants who received at least one dose of BAX 855.
|
|---|---|---|---|
|
Consumption of BAX 855: Weight-adjusted Dose Per Bleeding Episode
Average dose per infusion per bleeding episode
|
45.58 IU/kg
Standard Deviation 10.750
|
43.76 IU/kg
Standard Deviation 15.304
|
44.56 IU/kg
Standard Deviation 13.327
|
|
Consumption of BAX 855: Weight-adjusted Dose Per Bleeding Episode
Average dose to treat bleeding episode
|
52.21 IU/kg
Standard Deviation 16.681
|
62.31 IU/kg
Standard Deviation 38.764
|
57.85 IU/kg
Standard Deviation 31.041
|
SECONDARY outcome
Timeframe: After first exposure to BAX 855 until completion of study - approx. 6 months per participant.Population: Participants in the Full Analysis Set who had treated bleeding episodes.
Rating Scale for Treatment of Bleeding Episodes (BEs) (4-point ordinal scale): Excellent: Full relief of pain and cessation of objective signs of bleeding (eg, swelling, tenderness, and decreased range of motion in the case of musculoskeletal hemorrhage) after a single infusion. No additional infusion required for the control of bleeding. Administration of further infusions to maintain hemostasis did not affect this scoring. Good: Definite pain relief and/or improvement in signs of bleeding after a single infusion. 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 single infusion. Required more than 1 infusion for complete resolution. None: No improvement or condition worsens.
Outcome measures
| Measure |
<6 Years Old
n=25 bleeding episodes
Participants \< 6 years old who received at least one dose of BAX 855.
|
6 to <12 Years Old
n=45 bleeding episodes
Participants 6 to \<12 years old who received at least one dose of BAX 855.
|
BAX 855 Safety Analysis Set
n=70 bleeding episodes
Participants who received at least one dose of BAX 855.
|
|---|---|---|---|
|
Hemostatic Efficacy Rating for Bleeding Episodes Treated With BAX 855 at Resolution of Bleed
Excellent
|
15 bleeding episodes
|
19 bleeding episodes
|
34 bleeding episodes
|
|
Hemostatic Efficacy Rating for Bleeding Episodes Treated With BAX 855 at Resolution of Bleed
Good
|
9 bleeding episodes
|
20 bleeding episodes
|
29 bleeding episodes
|
|
Hemostatic Efficacy Rating for Bleeding Episodes Treated With BAX 855 at Resolution of Bleed
Fair
|
1 bleeding episodes
|
3 bleeding episodes
|
4 bleeding episodes
|
|
Hemostatic Efficacy Rating for Bleeding Episodes Treated With BAX 855 at Resolution of Bleed
Not reported
|
0 bleeding episodes
|
3 bleeding episodes
|
3 bleeding episodes
|
SECONDARY outcome
Timeframe: After first exposure to BAX 855 until completion of study - approx. 6 months per participant.Population: BAX 855 Safety Analysis Set.
Outcome measures
| Measure |
<6 Years Old
n=32 Participants
Participants \< 6 years old who received at least one dose of BAX 855.
|
6 to <12 Years Old
n=34 Participants
Participants 6 to \<12 years old who received at least one dose of BAX 855.
|
BAX 855 Safety Analysis Set
n=66 Participants
Participants who received at least one dose of BAX 855.
|
|---|---|---|---|
|
Serious Adverse Events (SAEs) Possibly or Probably Related to BAX 855
Investigator Assessment
|
0 serious adverse events
|
0 serious adverse events
|
0 serious adverse events
|
|
Serious Adverse Events (SAEs) Possibly or Probably Related to BAX 855
Sponsor Assessment
|
0 serious adverse events
|
0 serious adverse events
|
0 serious adverse events
|
SECONDARY outcome
Timeframe: After first exposure to BAX 855 until completion of study - approx. 6 months per participant.Population: BAX 855 Safety Analysis Set.
Outcome measures
| Measure |
<6 Years Old
n=32 Participants
Participants \< 6 years old who received at least one dose of BAX 855.
|
6 to <12 Years Old
n=34 Participants
Participants 6 to \<12 years old who received at least one dose of BAX 855.
|
BAX 855 Safety Analysis Set
n=66 Participants
Participants who received at least one dose of BAX 855.
|
|---|---|---|---|
|
Non-serious Adverse Events Possibly or Probably Related to BAX 855
Investigator Assessment
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
|
Non-serious Adverse Events Possibly or Probably Related to BAX 855
Sponsor Assessment
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
SECONDARY outcome
Timeframe: After first exposure to BAX 855 until completion of study - approx. 6 months per participant.Population: BAX 855 Safety Analysis Set.
Vital signs: body temperature (°C), respiratory rate (breaths/min), pulse rate (beats/min), and systolic and diastolic blood pressure (mmHg). For each vital sign value that changed from normal at baseline to abnormal at any subsequent study visit, the Investigator determined if the value was clinically significant (i.e. and adverse event), or not.
Outcome measures
| Measure |
<6 Years Old
n=32 Participants
Participants \< 6 years old who received at least one dose of BAX 855.
|
6 to <12 Years Old
n=34 Participants
Participants 6 to \<12 years old who received at least one dose of BAX 855.
|
BAX 855 Safety Analysis Set
n=66 Participants
Participants who received at least one dose of BAX 855.
|
|---|---|---|---|
|
Number of Participants With Clinically Significant Changes in Vital Signs
|
1 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: After first exposure to BAX 855 until completion of study - approx. 6 months per participant.Population: BAX 855 Safety Analysis Set.
The HEMATOLOGY PANEL consisted of complete blood count: hemoglobin, hematocrit, erythrocytes (ie, red blood cell count), leukocytes (ie, white blood cell count) with differential (ie, basophils, eosinophils, lymphocytes, monocytes, and neutrophils), mean corpuscular volume, mean corpuscular hemoglobin concentration, and platelet count. The CLINICAL CHEMISTRY PANEL consisted of sodium, potassium, chloride, bicarbonate, total protein, albumin, ALT, aspartate aminotransferase (AST), total bilirubin, alkaline phosphatase, blood urea nitrogen, creatinine, and glucose. The LIPID PANEL consisted of cholesterol, very low density lipoprotein, low density lipoprotein, high density lipoprotein, and triglycerides. For each laboratory parameter value that changed from normal at baseline to abnormal at any subsequent study visit, the Investigator determined if the value was clinically significant, or not.
Outcome measures
| Measure |
<6 Years Old
n=32 Participants
Participants \< 6 years old who received at least one dose of BAX 855.
|
6 to <12 Years Old
n=34 Participants
Participants 6 to \<12 years old who received at least one dose of BAX 855.
|
BAX 855 Safety Analysis Set
n=66 Participants
Participants who received at least one dose of BAX 855.
|
|---|---|---|---|
|
Number of Clinically Significant Changes in Clinical Laboratory Parameters (Hematology, Clinical Chemistry, Lipids)
Hematology-CS Rise in Eosinophils
|
1 clinically significant findings
|
0 clinically significant findings
|
1 clinically significant findings
|
|
Number of Clinically Significant Changes in Clinical Laboratory Parameters (Hematology, Clinical Chemistry, Lipids)
Clin. Chemistry-CS Rise in Alkaline Phosphatase
|
1 clinically significant findings
|
0 clinically significant findings
|
1 clinically significant findings
|
SECONDARY outcome
Timeframe: After first exposure to BAX 855 until completion of study - approx. 6 months per participant.Population: BAX 855 Safety Analysis Set: Data not available for 1 participant in the 6 to \<12 years group as participant was prematurely withdrawn from study.
Binding antibodies to FVIII and PEG-FVIII, as well as to PEG, were measured using enzyme-linked immunosorbent assay (ELISA). Both immunoglobulin G (IgG) and immunoglobulin M (IgM) binding antibodies for FVIII, BAX 855, and PEG were tested at each study visit. Testing for binding antibodies to CHO was performed on citrate-anti-coagulated plasma using an ELISA employing polyclonal anti-human IgG antibodies. This outcome measure includes antibodies that were transient (antibody developed after exposure to BAX 855 but not present at study termination/completion) and pre-existent (antibody originally present before exposure to BAX 855).
Outcome measures
| Measure |
<6 Years Old
n=32 Participants
Participants \< 6 years old who received at least one dose of BAX 855.
|
6 to <12 Years Old
n=33 Participants
Participants 6 to \<12 years old who received at least one dose of BAX 855.
|
BAX 855 Safety Analysis Set
n=65 Participants
Participants who received at least one dose of BAX 855.
|
|---|---|---|---|
|
Positive Post-baseline Binding Antibodies to Factor VIII (FVIII), Polyethylene Glycol-Factor VIII (PEG-FVIII), PEG and Chinese Hamster Ovary (CHO) Proteins
Positive binding IgM antibodies to PEG-FVIII
|
0 participants
|
0 participants
|
0 participants
|
|
Positive Post-baseline Binding Antibodies to Factor VIII (FVIII), Polyethylene Glycol-Factor VIII (PEG-FVIII), PEG and Chinese Hamster Ovary (CHO) Proteins
Positive binding IgG antibodies to FVIII
|
0 participants
|
0 participants
|
0 participants
|
|
Positive Post-baseline Binding Antibodies to Factor VIII (FVIII), Polyethylene Glycol-Factor VIII (PEG-FVIII), PEG and Chinese Hamster Ovary (CHO) Proteins
Positive binding IgM antibodies to FVIII
|
0 participants
|
0 participants
|
0 participants
|
|
Positive Post-baseline Binding Antibodies to Factor VIII (FVIII), Polyethylene Glycol-Factor VIII (PEG-FVIII), PEG and Chinese Hamster Ovary (CHO) Proteins
Positive binding IgG antibodies to PEG-FVIII
|
3 participants
|
4 participants
|
7 participants
|
|
Positive Post-baseline Binding Antibodies to Factor VIII (FVIII), Polyethylene Glycol-Factor VIII (PEG-FVIII), PEG and Chinese Hamster Ovary (CHO) Proteins
Positive binding IgG antibodies to PEG
|
0 participants
|
0 participants
|
0 participants
|
|
Positive Post-baseline Binding Antibodies to Factor VIII (FVIII), Polyethylene Glycol-Factor VIII (PEG-FVIII), PEG and Chinese Hamster Ovary (CHO) Proteins
Positive binding IgM antibodies to PEG
|
0 participants
|
0 participants
|
0 participants
|
|
Positive Post-baseline Binding Antibodies to Factor VIII (FVIII), Polyethylene Glycol-Factor VIII (PEG-FVIII), PEG and Chinese Hamster Ovary (CHO) Proteins
Positive binding Ig antibodies to CHO
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: (1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4Population: Pharmacokinetic (PK) Analysis Set.
The first PK infusion was ADVATE and the second PK infusion was BAX 855. All participants undergoing PK assessment had a 72-hour washout period before administration of ADVATE and BAX 855. There were 4 blood draws for PK analysis-1 pre-infusion and 3 post infusion. The timing of the infusion (morning \[am\] or afternoon \[pm\]) and the timing of Blood Draws 3 and 4 (3 groups for each blood draw) were determined at randomization. The sequence was as follows:- Blood Draw 1. within 30 minutes pre-infusion \[Day 0\]; PK INFUSION - am or pm \[Day 0\]; Blood Draw 2. 15-30 minutes post-infusion \[Day 0\]; Blood Draw 3. 3 groups:- 7 hours post-infusion (if am PK infusion) or 4 hours post-infusion (if pm PK infusion) \[Day 0\], Day 1 am or Day 1 pm; Blood Draw 4. 3 groups:- Day 2, Day 3 or Day 4. A nonlinear mixed effects model approach (population PK) was implemented to analyze PK data. A one-stage clotting assay was used as the primary assay and a chromogenic assay was used to provide supportive data.
Outcome measures
| Measure |
<6 Years Old
n=14 Participants
Participants \< 6 years old who received at least one dose of BAX 855.
|
6 to <12 Years Old
n=17 Participants
Participants 6 to \<12 years old who received at least one dose of BAX 855.
|
BAX 855 Safety Analysis Set
n=31 Participants
Participants who received at least one dose of BAX 855.
|
|---|---|---|---|
|
Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve From 0 to ∞ Hours Post-infusion (AUC0-∞)
Chromogenic assay - ADVATE
|
11600 IU•hr/L
Standard Deviation 3070
|
16600 IU•hr/L
Standard Deviation 3290
|
14400 IU•hr/L
Standard Deviation 4040
|
|
Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve From 0 to ∞ Hours Post-infusion (AUC0-∞)
One stage clotting assay - BAX 855
|
19500 IU•hr/L
Standard Deviation 7580
|
20100 IU•hr/L
Standard Deviation 4930
|
19800 IU•hr/L
Standard Deviation 6160
|
|
Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve From 0 to ∞ Hours Post-infusion (AUC0-∞)
One stage clotting assay - ADVATE
|
14000 IU•hr/L
Standard Deviation 3070
|
14400 IU•hr/L
Standard Deviation 1800
|
14200 IU•hr/L
Standard Deviation 2420
|
|
Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve From 0 to ∞ Hours Post-infusion (AUC0-∞)
Chromogenic assay - BAX 855
|
21900 IU•hr/L
Standard Deviation 15900
|
22600 IU•hr/L
Standard Deviation 5140
|
22300 IU•hr/L
Standard Deviation 11200
|
SECONDARY outcome
Timeframe: (1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4Population: The PK parameters were derived using a non-compartmental estimation approach using a flexible sampling design to provide point and interval estimates for summary PK parameter using a batch method. AUC/Dose is not a standard output parameter so this calculation was not done.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: (1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4Population: Pharmacokinetic (PK) Analysis Set
The first PK infusion was ADVATE and the second PK infusion was BAX 855. All participants undergoing PK assessment had a 72-hour washout period before administration of ADVATE and BAX 855. There were 4 blood draws for PK analysis-1 pre-infusion and 3 post infusion. The timing of the infusion (morning \[am\] or afternoon \[pm\]) and the timing of Blood Draws 3 and 4 (3 groups for each blood draw) were determined at randomization. The sequence was as follows:- Blood Draw 1. within 30 minutes pre-infusion \[Day 0\]; PK INFUSION - am or pm \[Day 0\]; Blood Draw 2. 15-30 minutes post-infusion \[Day 0\]; Blood Draw 3. 3 groups:- 7 hours post-infusion (if am PK infusion) or 4 hours post-infusion (if pm PK infusion) \[Day 0\], Day 1 am or Day 1 pm; Blood Draw 4. 3 groups:- Day 2, Day 3 or Day 4. A nonlinear mixed effects model approach (population PK) was implemented to analyze PK data. A one-stage clotting assay was used as the primary assay and a chromogenic assay was used to provide supportive data.
Outcome measures
| Measure |
<6 Years Old
n=14 Participants
Participants \< 6 years old who received at least one dose of BAX 855.
|
6 to <12 Years Old
n=17 Participants
Participants 6 to \<12 years old who received at least one dose of BAX 855.
|
BAX 855 Safety Analysis Set
n=31 Participants
Participants who received at least one dose of BAX 855.
|
|---|---|---|---|
|
Pharmacokinetics (PK): Mean Residence Time (MRT)
One stage clotting assay - ADVATE
|
13.3 hours (hr)
Standard Deviation 3.95
|
14.2 hours (hr)
Standard Deviation 2.64
|
13.8 hours (hr)
Standard Deviation 3.27
|
|
Pharmacokinetics (PK): Mean Residence Time (MRT)
Chromogenic assay - ADVATE
|
12.5 hours (hr)
Standard Deviation 2.52
|
11.6 hours (hr)
Standard Deviation 1.20
|
12.0 hours (hr)
Standard Deviation 1.93
|
|
Pharmacokinetics (PK): Mean Residence Time (MRT)
One stage clotting assay - BAX 855
|
17.0 hours (hr)
Standard Deviation 3.51
|
17.8 hours (hr)
Standard Deviation 2.40
|
17.5 hours (hr)
Standard Deviation 2.93
|
|
Pharmacokinetics (PK): Mean Residence Time (MRT)
Chromogenic assay - BAX 855
|
18.7 hours (hr)
Standard Deviation 12.6
|
17.2 hours (hr)
Standard Deviation 3.72
|
17.9 hours (hr)
Standard Deviation 8.76
|
SECONDARY outcome
Timeframe: (1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4Population: Pharmacokinetic (PK) Analysis Set
The first PK infusion was ADVATE and the second PK infusion was BAX 855. All participants undergoing PK assessment had a 72-hour washout period before administration of ADVATE and BAX 855. There were 4 blood draws for PK analysis-1 pre-infusion and 3 post infusion. The timing of the infusion (morning \[am\] or afternoon \[pm\]) and the timing of Blood Draws 3 and 4 (3 groups for each blood draw) were determined at randomization. The sequence was as follows:- Blood Draw 1. within 30 minutes pre-infusion \[Day 0\]; PK INFUSION - am or pm \[Day 0\]; Blood Draw 2. 15-30 minutes post-infusion \[Day 0\]; Blood Draw 3. 3 groups:- 7 hours post-infusion (if am PK infusion) or 4 hours post-infusion (if pm PK infusion) \[Day 0\], Day 1 am or Day 1 pm; Blood Draw 4. 3 groups:- Day 2, Day 3 or Day 4. A nonlinear mixed effects model approach (population PK) was implemented to analyze PK data. A one-stage clotting assay was used as the primary assay and a chromogenic assay was used to provide supportive data.
Outcome measures
| Measure |
<6 Years Old
n=14 Participants
Participants \< 6 years old who received at least one dose of BAX 855.
|
6 to <12 Years Old
n=17 Participants
Participants 6 to \<12 years old who received at least one dose of BAX 855.
|
BAX 855 Safety Analysis Set
n=31 Participants
Participants who received at least one dose of BAX 855.
|
|---|---|---|---|
|
Pharmacokinetics (PK): Clearance (CL)
One stage clotting assay - ADVATE
|
0.0775 L/hr
Standard Deviation 0.0132
|
0.1250 L/hr
Standard Deviation 0.04200
|
0.1030 L/hr
Standard Deviation 0.0398
|
|
Pharmacokinetics (PK): Clearance (CL)
Chromogenic assay - ADVATE
|
0.0933 L/hr
Standard Deviation 0.0106
|
0.1040 L/hr
Standard Deviation 0.00875
|
0.0994 L/hr
Standard Deviation 0.0110
|
|
Pharmacokinetics (PK): Clearance (CL)
One stage clotting assay - BAX 855
|
0.0596 L/hr
Standard Deviation 0.0190
|
0.0913 L/hr
Standard Deviation 0.0276
|
0.0770 L/hr
Standard Deviation 0.0286
|
|
Pharmacokinetics (PK): Clearance (CL)
Chromogenic assay - BAX 855
|
0.0574 L/hr
Standard Deviation 0.0174
|
0.0812 L/hr
Standard Deviation 0.0248
|
0.0704 L/hr
Standard Deviation 0.0246
|
SECONDARY outcome
Timeframe: (1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4Population: Pharmacokinetic (PK) Analysis Set
The first PK infusion was ADVATE and the second PK infusion was BAX 855. All participants undergoing PK assessment had a 72-hour washout period before administration of ADVATE and BAX 855. There were 4 blood draws for PK analysis-1 pre-infusion and 3 post infusion. The timing of the infusion (morning \[am\] or afternoon \[pm\]) and the timing of Blood Draws 3 and 4 (3 groups for each blood draw) were determined at randomization. The sequence was as follows:- Blood Draw 1. within 30 minutes pre-infusion \[Day 0\]; PK INFUSION - am or pm \[Day 0\]; Blood Draw 2. 15-30 minutes post-infusion \[Day 0\]; Blood Draw 3. 3 groups:- 7 hours post-infusion (if am PK infusion) or 4 hours post-infusion (if pm PK infusion) \[Day 0\], Day 1 am or Day 1 pm; Blood Draw 4. 3 groups:- Day 2, Day 3 or Day 4. A nonlinear mixed effects model approach (population PK) was implemented to analyze PK data. A one-stage clotting assay was used as the primary assay and a chromogenic assay was used to provide supportive data.
Outcome measures
| Measure |
<6 Years Old
n=14 Participants
Participants \< 6 years old who received at least one dose of BAX 855.
|
6 to <12 Years Old
n=17 Participants
Participants 6 to \<12 years old who received at least one dose of BAX 855.
|
BAX 855 Safety Analysis Set
n=31 Participants
Participants who received at least one dose of BAX 855.
|
|---|---|---|---|
|
Pharmacokinetics (PK): Plasma Half-life (T1/2)
One stage clotting assay - ADVATE
|
9.24 hours (hr)
Standard Deviation 2.74
|
9.82 hours (hr)
Standard Deviation 1.83
|
9.56 hours (hr)
Standard Deviation 2.26
|
|
Pharmacokinetics (PK): Plasma Half-life (T1/2)
Chromogenic assay - ADVATE
|
8.68 hours (hr)
Standard Deviation 1.75
|
8.04 hours (hr)
Standard Deviation 0.83
|
8.33 hours (hr)
Standard Deviation 1.34
|
|
Pharmacokinetics (PK): Plasma Half-life (T1/2)
One stage clotting assay - BAX 855
|
11.8 hours (hr)
Standard Deviation 2.43
|
12.4 hours (hr)
Standard Deviation 1.67
|
12.1 hours (hr)
Standard Deviation 2.03
|
|
Pharmacokinetics (PK): Plasma Half-life (T1/2)
Chromogenic assay - BAX 855
|
13.0 hours (hr)
Standard Deviation 8.74
|
11.9 hours (hr)
Standard Deviation 2.58
|
12.4 hours (hr)
Standard Deviation 6.07
|
SECONDARY outcome
Timeframe: (1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4Population: Pharmacokinetic (PK) Analysis Set
The first PK infusion was ADVATE and the second PK infusion was BAX 855. All participants undergoing PK assessment had a 72-hour washout period before administration of ADVATE and BAX 855. There were 4 blood draws for PK analysis-1 pre-infusion and 3 post infusion. The timing of the infusion (morning \[am\] or afternoon \[pm\]) and the timing of Blood Draws 3 and 4 (3 groups for each blood draw) were determined at randomization. The sequence was as follows:- Blood Draw 1. within 30 minutes pre-infusion \[Day 0\]; PK INFUSION - am or pm \[Day 0\]; Blood Draw 2. 15-30 minutes post-infusion \[Day 0\]; Blood Draw 3. 3 groups:- 7 hours post-infusion (if am PK infusion) or 4 hours post-infusion (if pm PK infusion) \[Day 0\], Day 1 am or Day 1 pm; Blood Draw 4. 3 groups:- Day 2, Day 3 or Day 4. A nonlinear mixed effects model approach (population PK) was implemented to analyze PK data. A one-stage clotting assay was used as the primary assay and a chromogenic assay was used to provide supportive data.
Outcome measures
| Measure |
<6 Years Old
n=14 Participants
Participants \< 6 years old who received at least one dose of BAX 855.
|
6 to <12 Years Old
n=17 Participants
Participants 6 to \<12 years old who received at least one dose of BAX 855.
|
BAX 855 Safety Analysis Set
n=31 Participants
Participants who received at least one dose of BAX 855.
|
|---|---|---|---|
|
Pharmacokinetics (PK): Volume of Distribution at Steady State (Vss)
One stage clotting assay - ADVATE
|
1.02 litre (L)
Standard Deviation 0.302
|
1.69 litre (L)
Standard Deviation 0.350
|
1.39 litre (L)
Standard Deviation 0.470
|
|
Pharmacokinetics (PK): Volume of Distribution at Steady State (Vss)
Chromogenic assay - ADVATE
|
1.14 litre (L)
Standard Deviation 0.107
|
1.20 litre (L)
Standard Deviation 0.0548
|
1.18 litre (L)
Standard Deviation 0.0857
|
|
Pharmacokinetics (PK): Volume of Distribution at Steady State (Vss)
One stage clotting assay - BAX 855
|
0.97 litre (L)
Standard Deviation 0.230
|
1.59 litre (L)
Standard Deviation 0.343
|
1.31 litre (L)
Standard Deviation 0.427
|
|
Pharmacokinetics (PK): Volume of Distribution at Steady State (Vss)
Chromogenic assay - BAX 855
|
0.907 litre (L)
Standard Deviation 0.124
|
1.33 litre (L)
Standard Deviation 0.233
|
1.14 litre (L)
Standard Deviation 0.285
|
SECONDARY outcome
Timeframe: (1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4Population: Pharmacokinetic (PK) Analysis Set
The first PK infusion was ADVATE and the second PK infusion was BAX 855. All participants undergoing PK assessment had a 72-hour washout period before administration of ADVATE and BAX 855. There were 4 blood draws for PK analysis-1 pre-infusion and 3 post infusion. The timing of the infusion (morning \[am\] or afternoon \[pm\]) and the timing of Blood Draws 3 and 4 (3 groups for each blood draw) were determined at randomization. The sequence was as follows:- Blood Draw 1. within 30 minutes pre-infusion \[Day 0\]; PK INFUSION - am or pm \[Day 0\]; Blood Draw 2. 15-30 minutes post-infusion \[Day 0\]; Blood Draw 3. 3 groups:- 7 hours post-infusion (if am PK infusion) or 4 hours post-infusion (if pm PK infusion) \[Day 0\], Day 1 am or Day 1 pm; Blood Draw 4. 3 groups:- Day 2, Day 3 or Day 4. A non-compartmental model approach was implemented to analyze IR data. A one-stage clotting assay was used as the primary assay and a chromogenic assay was used to provide supportive data.
Outcome measures
| Measure |
<6 Years Old
n=14 Participants
Participants \< 6 years old who received at least one dose of BAX 855.
|
6 to <12 Years Old
n=17 Participants
Participants 6 to \<12 years old who received at least one dose of BAX 855.
|
BAX 855 Safety Analysis Set
n=31 Participants
Participants who received at least one dose of BAX 855.
|
|---|---|---|---|
|
Pharmacokinetics (PK): Incremental Recovery (IR)
One stage clotting assay - ADVATE
|
1.8563 IU/dL : IU/kg
Standard Deviation 0.76004
|
1.8696 IU/dL : IU/kg
Standard Deviation 0.25856
|
1.8636 IU/dL : IU/kg
Standard Deviation 0.53481
|
|
Pharmacokinetics (PK): Incremental Recovery (IR)
Chromogenic assay - ADVATE
|
1.7374 IU/dL : IU/kg
Standard Deviation 0.29110
|
2.0458 IU/dL : IU/kg
Standard Deviation 0.31739
|
1.9065 IU/dL : IU/kg
Standard Deviation 0.33879
|
|
Pharmacokinetics (PK): Incremental Recovery (IR)
One stage clotting assay - BAX 855
|
1.8809 IU/dL : IU/kg
Standard Deviation 0.48894
|
1.9342 IU/dL : IU/kg
Standard Deviation 0.47451
|
1.9101 IU/dL : IU/kg
Standard Deviation 0.47371
|
|
Pharmacokinetics (PK): Incremental Recovery (IR)
Chromogenic assay - BAX 855
|
1.8813 IU/dL : IU/kg
Standard Deviation 0.27069
|
2.1710 IU/dL : IU/kg
Standard Deviation 0.38472
|
2.0402 IU/dL : IU/kg
Standard Deviation 0.36355
|
SECONDARY outcome
Timeframe: Baseline, Week 5 (or 10-15 EDs, whichever occurs last), Week 12, and Month 6 (Completion/Termination)Population: Participants from the Full Analysis Set who provided at least data from baseline, Week 5 (or 10-15 EDs, whichever occurred last), Week 12 or Month 6
Pre- and post-infusion levels of Factor VIII (FVIII) following infusion of BAX 855 were used to determine IR. For participants who underwent PK evaluation, baseline IR was determined from the IR measurement used in the PK analysis. Refer to data in Outcome measure 21- "Pharmacokinetics (PK): Incremental Recovery (IR)", for the category "One stage clotting assay - BAX 855" For participants who did not undergo a PK evaluation, baseline IR was determined at the baseline visit prior to the prophylactic treatment phase and is included in this outcome measure. Category title includes number of participants \[n\] \< 6 yrs; ≥6 to \<12 yrs and the Full Analysis Set, respectively.
Outcome measures
| Measure |
<6 Years Old
n=27 Participants
Participants \< 6 years old who received at least one dose of BAX 855.
|
6 to <12 Years Old
n=31 Participants
Participants 6 to \<12 years old who received at least one dose of BAX 855.
|
BAX 855 Safety Analysis Set
n=57 Participants
Participants who received at least one dose of BAX 855.
|
|---|---|---|---|
|
Pharmacokinetics (PK): Incremental Recovery (IR) of BAX 855 Over Time - One Stage Clotting Assay
Baseline [n=15, 16, 31]
|
1.6889 IU/dL : IU/kg
Standard Deviation 0.27610
|
1.7843 IU/dL : IU/kg
Standard Deviation 0.35942
|
1.7381 IU/dL : IU/kg
Standard Deviation 0.32017
|
|
Pharmacokinetics (PK): Incremental Recovery (IR) of BAX 855 Over Time - One Stage Clotting Assay
Week 5 (or after 10-15 EDs) [n= 27, 30, 57]
|
1.8952 IU/dL : IU/kg
Standard Deviation 0.55483
|
1.8661 IU/dL : IU/kg
Standard Deviation 0.49785
|
1.8799 IU/dL : IU/kg
Standard Deviation 0.52105
|
|
Pharmacokinetics (PK): Incremental Recovery (IR) of BAX 855 Over Time - One Stage Clotting Assay
Week 12 [n= 26, 31, 57]
|
1.6818 IU/dL : IU/kg
Standard Deviation 0.23069
|
1.9212 IU/dL : IU/kg
Standard Deviation 0.42496
|
1.8120 IU/dL : IU/kg
Standard Deviation 0.36738
|
|
Pharmacokinetics (PK): Incremental Recovery (IR) of BAX 855 Over Time - One Stage Clotting Assay
Month 6 (Termination/Completion) [n=27, 28, 55]
|
1.5801 IU/dL : IU/kg
Standard Deviation 0.31568
|
1.7120 IU/dL : IU/kg
Standard Deviation 0.36588
|
1.6472 IU/dL : IU/kg
Standard Deviation 0.34546
|
SECONDARY outcome
Timeframe: Baseline, Week 5 (or 10-15 Exposure Days [EDs], whichever occurs last), Week 12, and Month 6 (Completion/Termination)Population: Participants from the Full Analysis Set who provided at least data from baseline, Week 5 (or 10-15 EDs, whichever occurred last), Week 12 or Month 6.
Pre- and post-infusion levels of Factor VIII (FVIII) following infusion of BAX 855 were used to determine IR. For participants who underwent PK evaluation, baseline IR was determined from the IR measurement used in the PK analysis. Refer to data in Outcome measure 21- "Pharmacokinetics (PK): Incremental Recovery (IR)", for the category "Chromogenic assay - BAX 855" For participants who did not undergo a PK evaluation, baseline IR was determined at the baseline visit prior to the prophylactic treatment phase and is included in this outcome measure. Category title includes number of participants \[n\] \< 6 yrs; ≥6 to \<12 yrs and the Full Analysis Set, respectively.
Outcome measures
| Measure |
<6 Years Old
n=27 Participants
Participants \< 6 years old who received at least one dose of BAX 855.
|
6 to <12 Years Old
n=31 Participants
Participants 6 to \<12 years old who received at least one dose of BAX 855.
|
BAX 855 Safety Analysis Set
n=57 Participants
Participants who received at least one dose of BAX 855.
|
|---|---|---|---|
|
Pharmacokinetics (PK): Incremental Recovery (IR) of BAX 855 Over Time - Chromogenic Assay
Baseline [n= 15; 16; 31]
|
1.7675 IU/dL : IU/kg
Standard Deviation 0.34998
|
1.9334 IU/dL : IU/kg
Standard Deviation 0.30000
|
1.8532 IU/dL : IU/kg
Standard Deviation 0.33055
|
|
Pharmacokinetics (PK): Incremental Recovery (IR) of BAX 855 Over Time - Chromogenic Assay
Week 5 (or after 10-15 EDs) [n= 27; 30; 57]
|
1.9273 IU/dL : IU/kg
Standard Deviation 0.32400
|
1.9960 IU/dL : IU/kg
Standard Deviation 0.39258
|
1.9635 IU/dL : IU/kg
Standard Deviation 0.36021
|
|
Pharmacokinetics (PK): Incremental Recovery (IR) of BAX 855 Over Time - Chromogenic Assay
Week 12 [n= 26; 31; 57]
|
1.8794 IU/dL : IU/kg
Standard Deviation 0.24281
|
1.9869 IU/dL : IU/kg
Standard Deviation 0.42300
|
1.9379 IU/dL : IU/kg
Standard Deviation 0.35368
|
|
Pharmacokinetics (PK): Incremental Recovery (IR) of BAX 855 Over Time - Chromogenic Assay
Month 6 (Termination/Completion) [n= 27; 28; 55]
|
1.8359 IU/dL : IU/kg
Standard Deviation 0.29188
|
2.0659 IU/dL : IU/kg
Standard Deviation 0.45723
|
1.9530 IU/dL : IU/kg
Standard Deviation 0.39876
|
POST_HOC outcome
Timeframe: (1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4Population: Pharmacokinetic (PK) Analysis Set
This is a descriptive summary of the ratio of plasma half-life in the same subject for BAX 855 compared to ADVATE based on the final covariate model (first observation tabulation).
Outcome measures
| Measure |
<6 Years Old
n=31 Participants
Participants \< 6 years old who received at least one dose of BAX 855.
|
6 to <12 Years Old
Participants 6 to \<12 years old who received at least one dose of BAX 855.
|
BAX 855 Safety Analysis Set
Participants who received at least one dose of BAX 855.
|
|---|---|---|---|
|
Pharmacokinetics (PK): Plasma Half-life Ratio of BAX 855 to ADVATE
One stage clotting assay
|
1.30 hours (hr)
Interval 0.944 to 2.0
|
—
|
—
|
|
Pharmacokinetics (PK): Plasma Half-life Ratio of BAX 855 to ADVATE
Chromogenic assay
|
1.50 hours (hr)
Interval 0.894 to 4.81
|
—
|
—
|
Adverse Events
BAX 855 Safety Analysis Set
ADVATE Received Before BAX 855
Serious adverse events
| Measure |
BAX 855 Safety Analysis Set
n=66 participants at risk
Participants who received at least 1 dose of BAX 855.
|
ADVATE Received Before BAX 855
n=31 participants at risk
Participants who received at least 1 dose of ADVATE prior to receiving BAX 855 in the PK part of the study.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal Pain
|
1.5%
1/66 • Number of events 1 • Throughout the study period of 1 year (8-10 months per participant)
AEs were continuously monitored but specifically discussed and reviewed at these time points: pre- and post-PK infusion, at the baseline visit, during prophylactic treatment at these visits: Week 5 (or 10-15 exposure days (EDs)), Week 12, Week 20 (by phone); at the study completion visit at Month 6 or after at least 50 EDs, whichever occurred last.
|
0.00%
0/31 • Throughout the study period of 1 year (8-10 months per participant)
AEs were continuously monitored but specifically discussed and reviewed at these time points: pre- and post-PK infusion, at the baseline visit, during prophylactic treatment at these visits: Week 5 (or 10-15 exposure days (EDs)), Week 12, Week 20 (by phone); at the study completion visit at Month 6 or after at least 50 EDs, whichever occurred last.
|
|
Gastrointestinal disorders
Gastritis
|
1.5%
1/66 • Number of events 1 • Throughout the study period of 1 year (8-10 months per participant)
AEs were continuously monitored but specifically discussed and reviewed at these time points: pre- and post-PK infusion, at the baseline visit, during prophylactic treatment at these visits: Week 5 (or 10-15 exposure days (EDs)), Week 12, Week 20 (by phone); at the study completion visit at Month 6 or after at least 50 EDs, whichever occurred last.
|
0.00%
0/31 • Throughout the study period of 1 year (8-10 months per participant)
AEs were continuously monitored but specifically discussed and reviewed at these time points: pre- and post-PK infusion, at the baseline visit, during prophylactic treatment at these visits: Week 5 (or 10-15 exposure days (EDs)), Week 12, Week 20 (by phone); at the study completion visit at Month 6 or after at least 50 EDs, whichever occurred last.
|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
1.5%
1/66 • Number of events 1 • Throughout the study period of 1 year (8-10 months per participant)
AEs were continuously monitored but specifically discussed and reviewed at these time points: pre- and post-PK infusion, at the baseline visit, during prophylactic treatment at these visits: Week 5 (or 10-15 exposure days (EDs)), Week 12, Week 20 (by phone); at the study completion visit at Month 6 or after at least 50 EDs, whichever occurred last.
|
0.00%
0/31 • Throughout the study period of 1 year (8-10 months per participant)
AEs were continuously monitored but specifically discussed and reviewed at these time points: pre- and post-PK infusion, at the baseline visit, during prophylactic treatment at these visits: Week 5 (or 10-15 exposure days (EDs)), Week 12, Week 20 (by phone); at the study completion visit at Month 6 or after at least 50 EDs, whichever occurred last.
|
|
Blood and lymphatic system disorders
Pancytopenia
|
1.5%
1/66 • Number of events 1 • Throughout the study period of 1 year (8-10 months per participant)
AEs were continuously monitored but specifically discussed and reviewed at these time points: pre- and post-PK infusion, at the baseline visit, during prophylactic treatment at these visits: Week 5 (or 10-15 exposure days (EDs)), Week 12, Week 20 (by phone); at the study completion visit at Month 6 or after at least 50 EDs, whichever occurred last.
|
0.00%
0/31 • Throughout the study period of 1 year (8-10 months per participant)
AEs were continuously monitored but specifically discussed and reviewed at these time points: pre- and post-PK infusion, at the baseline visit, during prophylactic treatment at these visits: Week 5 (or 10-15 exposure days (EDs)), Week 12, Week 20 (by phone); at the study completion visit at Month 6 or after at least 50 EDs, whichever occurred last.
|
Other adverse events
| Measure |
BAX 855 Safety Analysis Set
n=66 participants at risk
Participants who received at least 1 dose of BAX 855.
|
ADVATE Received Before BAX 855
n=31 participants at risk
Participants who received at least 1 dose of ADVATE prior to receiving BAX 855 in the PK part of the study.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
7.6%
5/66 • Number of events 5 • Throughout the study period of 1 year (8-10 months per participant)
AEs were continuously monitored but specifically discussed and reviewed at these time points: pre- and post-PK infusion, at the baseline visit, during prophylactic treatment at these visits: Week 5 (or 10-15 exposure days (EDs)), Week 12, Week 20 (by phone); at the study completion visit at Month 6 or after at least 50 EDs, whichever occurred last.
|
0.00%
0/31 • Throughout the study period of 1 year (8-10 months per participant)
AEs were continuously monitored but specifically discussed and reviewed at these time points: pre- and post-PK infusion, at the baseline visit, during prophylactic treatment at these visits: Week 5 (or 10-15 exposure days (EDs)), Week 12, Week 20 (by phone); at the study completion visit at Month 6 or after at least 50 EDs, whichever occurred last.
|
|
Gastrointestinal disorders
Vomiting
|
7.6%
5/66 • Number of events 6 • Throughout the study period of 1 year (8-10 months per participant)
AEs were continuously monitored but specifically discussed and reviewed at these time points: pre- and post-PK infusion, at the baseline visit, during prophylactic treatment at these visits: Week 5 (or 10-15 exposure days (EDs)), Week 12, Week 20 (by phone); at the study completion visit at Month 6 or after at least 50 EDs, whichever occurred last.
|
0.00%
0/31 • Throughout the study period of 1 year (8-10 months per participant)
AEs were continuously monitored but specifically discussed and reviewed at these time points: pre- and post-PK infusion, at the baseline visit, during prophylactic treatment at these visits: Week 5 (or 10-15 exposure days (EDs)), Week 12, Week 20 (by phone); at the study completion visit at Month 6 or after at least 50 EDs, whichever occurred last.
|
|
General disorders
Pyrexia
|
19.7%
13/66 • Number of events 20 • Throughout the study period of 1 year (8-10 months per participant)
AEs were continuously monitored but specifically discussed and reviewed at these time points: pre- and post-PK infusion, at the baseline visit, during prophylactic treatment at these visits: Week 5 (or 10-15 exposure days (EDs)), Week 12, Week 20 (by phone); at the study completion visit at Month 6 or after at least 50 EDs, whichever occurred last.
|
0.00%
0/31 • Throughout the study period of 1 year (8-10 months per participant)
AEs were continuously monitored but specifically discussed and reviewed at these time points: pre- and post-PK infusion, at the baseline visit, during prophylactic treatment at these visits: Week 5 (or 10-15 exposure days (EDs)), Week 12, Week 20 (by phone); at the study completion visit at Month 6 or after at least 50 EDs, whichever occurred last.
|
|
Infections and infestations
Nasopharyngitis
|
7.6%
5/66 • Number of events 5 • Throughout the study period of 1 year (8-10 months per participant)
AEs were continuously monitored but specifically discussed and reviewed at these time points: pre- and post-PK infusion, at the baseline visit, during prophylactic treatment at these visits: Week 5 (or 10-15 exposure days (EDs)), Week 12, Week 20 (by phone); at the study completion visit at Month 6 or after at least 50 EDs, whichever occurred last.
|
0.00%
0/31 • Throughout the study period of 1 year (8-10 months per participant)
AEs were continuously monitored but specifically discussed and reviewed at these time points: pre- and post-PK infusion, at the baseline visit, during prophylactic treatment at these visits: Week 5 (or 10-15 exposure days (EDs)), Week 12, Week 20 (by phone); at the study completion visit at Month 6 or after at least 50 EDs, whichever occurred last.
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
13.6%
9/66 • Number of events 9 • Throughout the study period of 1 year (8-10 months per participant)
AEs were continuously monitored but specifically discussed and reviewed at these time points: pre- and post-PK infusion, at the baseline visit, during prophylactic treatment at these visits: Week 5 (or 10-15 exposure days (EDs)), Week 12, Week 20 (by phone); at the study completion visit at Month 6 or after at least 50 EDs, whichever occurred last.
|
0.00%
0/31 • Throughout the study period of 1 year (8-10 months per participant)
AEs were continuously monitored but specifically discussed and reviewed at these time points: pre- and post-PK infusion, at the baseline visit, during prophylactic treatment at these visits: Week 5 (or 10-15 exposure days (EDs)), Week 12, Week 20 (by phone); at the study completion visit at Month 6 or after at least 50 EDs, whichever occurred last.
|
|
Nervous system disorders
Headache
|
7.6%
5/66 • Number of events 7 • Throughout the study period of 1 year (8-10 months per participant)
AEs were continuously monitored but specifically discussed and reviewed at these time points: pre- and post-PK infusion, at the baseline visit, during prophylactic treatment at these visits: Week 5 (or 10-15 exposure days (EDs)), Week 12, Week 20 (by phone); at the study completion visit at Month 6 or after at least 50 EDs, whichever occurred last.
|
0.00%
0/31 • Throughout the study period of 1 year (8-10 months per participant)
AEs were continuously monitored but specifically discussed and reviewed at these time points: pre- and post-PK infusion, at the baseline visit, during prophylactic treatment at these visits: Week 5 (or 10-15 exposure days (EDs)), Week 12, Week 20 (by phone); at the study completion visit at Month 6 or after at least 50 EDs, whichever occurred last.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.1%
4/66 • Number of events 8 • Throughout the study period of 1 year (8-10 months per participant)
AEs were continuously monitored but specifically discussed and reviewed at these time points: pre- and post-PK infusion, at the baseline visit, during prophylactic treatment at these visits: Week 5 (or 10-15 exposure days (EDs)), Week 12, Week 20 (by phone); at the study completion visit at Month 6 or after at least 50 EDs, whichever occurred last.
|
0.00%
0/31 • Throughout the study period of 1 year (8-10 months per participant)
AEs were continuously monitored but specifically discussed and reviewed at these time points: pre- and post-PK infusion, at the baseline visit, during prophylactic treatment at these visits: Week 5 (or 10-15 exposure days (EDs)), Week 12, Week 20 (by phone); at the study completion visit at Month 6 or after at least 50 EDs, whichever occurred last.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Baxalta's agreements with PIs may vary per requirements of individual PI, but contain common elements. For this study, results may not be published without prior written approval of Sponsor.
- Publication restrictions are in place
Restriction type: OTHER