BAY81-8973 Pediatric Safety and Efficacy Trial
Sponsor
Bayer (Industry)
Overall Status
Completed
CT.gov ID
NCT01311648
Collaborator
(none)
94
43
2
112.6
2.2
0
Study Details
Study Description
Brief Summary
The primary objective was to evaluate the safety and efficacy of the treatment with BAY81-8973 for prophylaxis and treatment of breakthrough bleeds in children with severe hemophilia A.
The secondary objectives were
-
To assess the safety and efficacy of BAY81-8973 during surgeries.
-
To assess incremental recovery of BAY81-8973.
-
To assess pharmacokinetic (PK) parameters in a subset of children (Previously treated patients [PTPs] and previously untreated patients [PUPs] / minimally treated patients [MTPs] - participation in PK sampling was voluntary and required consent).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
94 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multicenter Phase III Uncontrolled Open-label Trial to Evaluate Safety and Efficacy of BAY81-8973 in Children With Severe Hemophilia A Under Prophylaxis Therapy
Actual Study Start Date
:
Jun 9, 2011
Actual Primary Completion Date
:
Sep 9, 2019
Actual Study Completion Date
:
Oct 27, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: PTPs 0-12 years Previously treated patients (PTPs) aged below 12 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (EDs) in main study - Part A. Participants having reached at least 50 EDs in main study - Part A were offered participation in an open label extension study (optional). Participants who transitioned from main study - Part A to the extension study received BAY81-8973, 25-50 IU/kg at least 2x/week for at least 100 cumulative EDs (main study - Part A and extension study). |
Biological: Recombinant Factor VIII (Kovaltry, BAY81-8973)
Main study: 25-50 IU/kg at least 2x/week for 6 months and at least 50 EDs, IV infusion; Extension study: 25-50 IU/kg at least 2x/week for at least 100 cumulative EDs (main study - Part A and extension study), IV infusion. Exposure day (ED): An ED is a unit of time (1 day) in which replacement treatment of Hemophilia is given to a patient.
|
| Experimental: PUPs/MTPs 0-<6 years Previously untreated patients (PUPs) or minimally treated patients (MTPs, patients who had no more than 3 exposure days (EDs) with any FVIII product) received BAY81-8973 15-50 IU/kg at least 1x/week for at least 50 EDs or until inhibitor development in main study - Part B. Participants having reached at least 50 EDs in main study - Part B were offered participation in an open label extension study and received BAY81-8973 25-50 IU/kg at least 2x/week for at least 100 cumulative EDs (main study - Part B and extension study); participants who developed an inhibitor in main study - Part B were offered participation in open label extension study and received Immune Tolerance Induction (ITI) treatment with BAY81-8973 until successful eradication of the inhibitor, or until failure, for approximately 18 months. |
Biological: Recombinant Factor VIII (Kovaltry, BAY81-8973)
Main study: 15-50 IU/kg at least 1x/week for at least 50 EDs or until inhibitor development, IV infusion; Extension study: For participants having reached at least 50 EDs in main study - Part B: 25-50 IU/kg at least 2x/week for at least 100 cumulative EDs (main study - Part B and extension study), IV infusion. For participants who developed an inhibitor in main study - Part B: up to 200 IU/kg per day or 100 IU/kg twice a day at the discretion of the investigator and coordinating investigator until successful eradication of the inhibitor, or until failure, for up to18 months (treatment beyond 18 months required an agreement with the sponsor and coordinating investigator), IV infusion
|
Outcome Measures
Primary Outcome Measures
- Annualized Number of Total Bleeds Within 48 h [Within 48 hours post infusion]
Annualized number (mean +/- standard deviation) of total bleeds that occurred within 48 hours after all prophylaxis infusions (Part A: 6 months and at least 50 exposure days [EDs]; Part B: at least 50 EDs or until inhibitor development) was summarized and reported. Total bleeds: sum of spontaneous bleeds, trauma bleeds (only treated bleeds were classified as spontaneous or trauma), untreated bleeds and 'other' bleeds ('other' bleeds were infusions with reason given as 'other').
- Annualized Number of Total Bleeds Within 48 h [Within 48 hours post infusion]
Annualized number (median [inter-quartile range (Q1-Q3)]) of total bleeds that occurred within 48 hours after all prophylaxis infusions (Part A: 6 months and at least 50 exposure days [EDs]; Part B: at least 50 EDs or until inhibitor development) was summarized and reported. Total bleeds: sum of spontaneous bleeds, trauma bleeds (only treated bleeds were classified as spontaneous or trauma), untreated bleeds and 'other' bleeds ('other' bleeds were infusions with reason given as 'other').
Secondary Outcome Measures
- Annualized Number of Total Bleeds During Prophylaxis Treatment [Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)]
Annualized number (mean +/- standard deviation) of total bleeds that occurred during prophylaxis treatment was summarized and reported. Total bleeds: sum of spontaneous bleeds, trauma bleeds (only treated bleeds were classified as spontaneous or trauma), untreated bleeds and 'other' bleeds ('other' bleeds were infusions with reason given as 'other').
- Annualized Number of Total Bleeds During Prophylaxis Treatment [Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)]
Annualized number (median [inter-quartile range (Q1-Q3)]) of total bleeds that occurred during prophylaxis treatment was summarized and reported. Total bleeds: sum of spontaneous bleeds, trauma bleeds (only treated bleeds were classified as spontaneous or trauma), untreated bleeds and 'other' bleeds ('other' bleeds were infusions with reason given as 'other').
- Hemostatic Control During Major and Minor Surgeries [Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)]
For participants who underwent major or minor surgeries during the study, hemostasis during the surgeries was assessed as excellent, good, moderate or poor. Number of surgeries per assessment was summarized and reported.
- Number of Participants With Inhibitor Development in Main Study [Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)]
Number of participants with confirmed positive FVIII inhibitor titer (≥ 0.6 Bethesda unit [BU/mL]) during the main study was summarized and classified as participants developing low titer inhibitor (i.e. ≥ 0.6 to ≤ 5.0 BU/mL) and participants developing high titer inhibitor (i.e. > 5.0 BU/mL).
- Number of Participants With New Inhibitor Development in Extension Study [From start of extension study to at least 100 cumulative exposure days (EDs) (median 421 EDs; median 3.8 years)]
Number of participants who had not developed an inhibitor during the main study but developed an inhibitor (confirmed positive FVIII inhibitor titer [≥ 0.6 BU/mL]) during the extension study was summarized and classified as participants developing low titer inhibitor (i.e. ≥ 0.6 to ≤ 5.0 BU/mL) and participants developing high titer inhibitor (i.e. > 5.0 BU/mL).
- Factor VIII Recovery Values [Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)]
Incremental recovery of Factor VIII (FVIII) at 20-30 min after end of infusions was determined and mean recovery values were reported.
- Consumption of Factor VIII in All Infusions [Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)]
Factor VIII (FVIII) usage/consumption was summarized for all infusions. Consumption per participant's body weight per year was calculated and reported.
- Consumption of FVIII in Infusions for Prophylaxis [Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)]
Factor VIII (FVIII) usage/consumption was summarized for prophylaxis infusions. Consumption per participant's body weight per year was calculated and reported.
- Consumption of FVIII in Infusions for the Treatment of Bleeds [Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)]
Factor VIII (FVIII) usage/consumption was summarized for infusions used to treat breakthrough bleeds. Consumption per participant's body weight per year was calculated and reported.
- Number of Infusions Per Bleed [Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)]
The number of infusions used to treat a bleed was defined as the first infusion to treat the bleed plus all follow-up infusions to treat the same bleed, if any. The mean value of number of infusions for each bleed was calculated and reported.
- Response to Treatment of Bleeds [Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)]
Participants or caregivers were asked to assess the response to treatment of bleeds as excellent, good, moderate or poor. Percentage of bleeds per assessment was summarized and reported.
- Half-life (t1/2) of BAY81-8973 in Plasma [Pre-infusion and until 24 hours post infusion]
Half-life (t1/2) of BAY81-8973 in plasma was measured. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Eligibility Criteria
Criteria
Ages Eligible for Study:
0 Years
to 12 Years
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Male
-
PTPs (previously treated patients): aged <= 12 years
-
PUPs (previously untreated patients) / MTPs (minimally treated patients): aged < 6 years
-
Severe hemophilia A defined as < 1% FVIII concentration (FVIII:C)
-
PTPs: >= 50 exposure days (EDs) with any FVIII concentrate, no current evidence of inhibitory antibody, and no history of FVIII inhibitor formation
-
PUPs: no prior exposure to any FVIII product
-
MTPs: having no more than 3 EDs with any FVIII product, no current evidence of inhibitory antibody and no history of FVIII inhibitor formation
Exclusion Criteria:
-
With another bleeding disorder that is different from Hemophilia A
-
With thrombocytopenia (platelet count < 100 000/mm^3)
-
Creatinine > 2x upper limit of normal or Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) > 5x upper limit of normal
-
Without a negative inhibitor testing at screening (except for PUPs)
-
Receiving chemotherapy, immune modulatory drugs, has received another investigational FVIII product within the last month, or received another experimental drug within the last 3 months
-
Requires any pre-medication to tolerate FVIII treatment
-
Known hypersensitivity to active substance, mouse, or hamster protein
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | New Orleans | Louisiana | United States | 70112 | |
| 2 | Cincinnati | Ohio | United States | 45229 | |
| 3 | Cleveland | Ohio | United States | 44106 | |
| 4 | Columbus | Ohio | United States | 43205-2696 | |
| 5 | Bahía Blanca | Buenos Aires | Argentina | B8001HXM | |
| 6 | Plovdiv | Bulgaria | 4002 | ||
| 7 | Varna | Bulgaria | 9010 | ||
| 8 | Edmonton | Alberta | Canada | T6G 2C8 | |
| 9 | Hamilton | Ontario | Canada | L8N 3Z5 | |
| 10 | Toronto | Ontario | Canada | M5G 1X8 | |
| 11 | Århus N | Denmark | 8200 | ||
| 12 | Budapest | Hungary | 1089 | ||
| 13 | Debrecen | Hungary | 4032 | ||
| 14 | Mohacs | Hungary | 7700 | ||
| 15 | Crumlin | Dublin | Ireland | 12 | |
| 16 | Ramat Gan | Israel | 5262000 | ||
| 17 | Roma | Lazio | Italy | 00165 | |
| 18 | Milano | Lombardia | Italy | 20122 | |
| 19 | Bari | Puglia | Italy | 70126 | |
| 20 | Catania | Sicilia | Italy | 95123 | |
| 21 | Padova | Veneto | Italy | 35128 | |
| 22 | Riga | Latvia | LV-1004 | ||
| 23 | Vilnius | Lithuania | 08406 | ||
| 24 | Guadalajara | Jalisco | Mexico | 44280 | |
| 25 | San Juan del Río | Querétaro | Mexico | 76800 | |
| 26 | Oaxaca | Mexico | 68000 | ||
| 27 | Oslo | Norway | |||
| 28 | Lodz | Poland | 91-738 | ||
| 29 | Warszawa | Poland | 00-576 | ||
| 30 | Wroclaw | Poland | 50-368 | ||
| 31 | Bucharest | Romania | 011026 | ||
| 32 | Bucharest | Romania | 022328 | ||
| 33 | Cluj-Napoca | Romania | 400177 | ||
| 34 | Timisoara | Romania | 300011 | ||
| 35 | Kazan | Russian Federation | 139445 | ||
| 36 | Kirov | Russian Federation | 610027 | ||
| 37 | Volgograd | Russian Federation | 400138 | ||
| 38 | Esplugues de LLobregat | Barcelona | Spain | 08950 | |
| 39 | A Coruña | Spain | 15006 | ||
| 40 | Alicante | Spain | 03010 | ||
| 41 | Cáceres | Spain | 10003 | ||
| 42 | Madrid | Spain | 28046 | ||
| 43 | Valencia | Spain | 46026 |
Sponsors and Collaborators
- Bayer
Investigators
- Study Director: Bayer Study Director, Bayer
Study Documents (Full-Text)
More Information
Additional Information:
- Click here to find information about studies related to Bayer Healthcare products conducted in Europe
- Click here to find results for studies related to Bayer products
Publications
None provided.Responsible Party:
Bayer
ClinicalTrials.gov Identifier:
NCT01311648
Other Study ID Numbers:
- 13400
- 2010-021781-29
First Posted:
Mar 9, 2011
Last Update Posted:
Nov 17, 2021
Last Verified:
Nov 1, 2021
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Bayer
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | The study was conducted at multiple centers in 18 countries and consisted of: Part A - between 09-JUN-2011 (FPFV) and 02-JAN-2013 (LPLV); Part B - between 19-SEP-2012 (FPFV) and 09-SEP-2019 (LPLV); Extension study - between 21-DEC-2011 (FPFV) and 27-OCT-2020 (LPLV). |
|---|---|
| Pre-assignment Detail | Overall, 58 participants were screened in Part A, of which 7 participants were screening failures and 51 participants received the study drug; 52 participants were screened in Part B, of which 9 participants were screening failures and 43 participants received the study drug. 46 participants from Part A and 36 from Part B entered the optional extension study. |
| Arm/Group Title | PTPs 0-12 Years | PUPs/MTPs 0-<6 Years |
|---|---|---|
| Arm/Group Description | Previously treated patients (PTPs) aged below 12 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (EDs) in main study - Part A. Participants having reached at least 50 EDs in main study - Part A were offered participation in an open label extension study (optional). Participants who transitioned from main study - Part A to the extension study received BAY81-8973, 25-50 IU/kg at least 2x/week for at least 100 cumulative EDs (main study - Part A and extension study). | Previously untreated patients (PUPs) or minimally treated patients (MTPs, patients who had no more than 3 exposure days [EDs] with any FVIII product) received BAY81-8973 15-50 IU/kg at least 1x/week for at least 50 EDs or until inhibitor development in main study - Part B. Participants having reached at least 50 EDs in main study - Part B were offered participation in an open label extension study and received BAY81-8973 25-50 IU/kg at least 2x/week for at least 100 cumulative EDs (main study - Part B and extension study); participants who developed an inhibitor in main study - Part B were offered participation in open label extension study and received Immune Tolerance Induction (ITI) treatment with BAY81-8973 until successful eradication of the inhibitor, or until failure, for approximately 18 months. |
| Period Title: Main Study | ||
| STARTED | 51 | 43 |
| Started 0-<6 Years | 25 | 43 |
| Started 6-12 Years | 26 | 0 |
| COMPLETED | 51 | 22 |
| NOT COMPLETED | 0 | 21 |
| Period Title: Main Study | ||
| STARTED | 46 | 36 |
| COMPLETED | 45 | 25 |
| NOT COMPLETED | 1 | 11 |
Baseline Characteristics
| Arm/Group Title | Main Study - Part A: PTPs 0-<6 Years | Main Study - Part A: PTPs 6-12 Years | Main Study - Part B: PUPs/MTPs 0-<6 Years | Total |
|---|---|---|---|---|
| Arm/Group Description | Previously treated patients (PTPs) aged below 6 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED) in main study - Part A. | Previously treated patients (PTPs) aged 6 to 12 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED) in main study - Part A. | Previously untreated patients (PUPs) or minimally treated patients (MTPs, patients who had no more then 3 exposure days (EDs) with any FVIII product) received BAY81-8973 15-50 IU/kg at least 1x/week for 50 EDs or until inhibitor development in main study - Part B. | Total of all reporting groups |
| Overall Participants | 25 | 26 | 43 | 94 |
| Age (Years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Years] |
3.8
(1.3)
|
8.8
(1.8)
|
1.1
(0.8)
|
3.9
(3.4)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Male |
25
100%
|
26
100%
|
43
100%
|
94
100%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
1
4%
|
0
0%
|
9
20.9%
|
10
10.6%
|
| Not Hispanic or Latino |
23
92%
|
25
96.2%
|
34
79.1%
|
82
87.2%
|
| Unknown or Not Reported |
1
4%
|
1
3.8%
|
0
0%
|
2
2.1%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||
| White |
24
96%
|
24
92.3%
|
37
86%
|
85
90.4%
|
| Black |
1
4%
|
2
7.7%
|
1
2.3%
|
4
4.3%
|
| American Indian or Alaska native |
0
0%
|
0
0%
|
1
2.3%
|
1
1.1%
|
| White, American Indian or Alaska native |
0
0%
|
0
0%
|
1
2.3%
|
1
1.1%
|
| Not reported |
0
0%
|
0
0%
|
3
7%
|
3
3.2%
|
Outcome Measures
| Title | Annualized Number of Total Bleeds Within 48 h |
|---|---|
| Description | Annualized number (mean +/- standard deviation) of total bleeds that occurred within 48 hours after all prophylaxis infusions (Part A: 6 months and at least 50 exposure days [EDs]; Part B: at least 50 EDs or until inhibitor development) was summarized and reported. Total bleeds: sum of spontaneous bleeds, trauma bleeds (only treated bleeds were classified as spontaneous or trauma), untreated bleeds and 'other' bleeds ('other' bleeds were infusions with reason given as 'other'). |
| Time Frame | Within 48 hours post infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) analysis set - main study: all participants of the SAF in main study who had infusion/bleeding data from the electronic patient diary (EPD) |
| Arm/Group Title | Main Study - Part A: PTPs 0-<6 Years | Main Study - Part A: PTPs 6-12 Years | Main Study - Part B: PUPs/MTPs 0-<6 Years |
|---|---|---|---|
| Arm/Group Description | Previously treated patients (PTPs) aged below 6 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED) in main study - Part A. | Previously treated patients (PTPs) aged 6 to 12 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED) in main study - Part A. | Previously untreated patients (PUPs) or minimally treated patients (MTPs, patients who had no more then 3 exposure days (EDs) with any FVIII product) received BAY81-8973 15-50 IU/kg at least 1x/week for 50 EDs or until inhibitor development in main study - Part B. |
| Measure Participants | 25 | 26 | 43 |
| Mean (Standard Deviation) [Bleeds] |
2.23
(2.77)
|
1.86
(3.08)
|
1.9
(3.3)
|
| Title | Annualized Number of Total Bleeds Within 48 h |
|---|---|
| Description | Annualized number (median [inter-quartile range (Q1-Q3)]) of total bleeds that occurred within 48 hours after all prophylaxis infusions (Part A: 6 months and at least 50 exposure days [EDs]; Part B: at least 50 EDs or until inhibitor development) was summarized and reported. Total bleeds: sum of spontaneous bleeds, trauma bleeds (only treated bleeds were classified as spontaneous or trauma), untreated bleeds and 'other' bleeds ('other' bleeds were infusions with reason given as 'other'). |
| Time Frame | Within 48 hours post infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) analysis set - main study: all participants of the SAF in main study who had infusion/bleeding data from the electronic patient diary (EPD) |
| Arm/Group Title | Main Study - Part A: PTPs 0-<6 Years | Main Study - Part A: PTPs 6-12 Years | Main Study - Part B: PUPs/MTPs 0-<6 Years |
|---|---|---|---|
| Arm/Group Description | Previously treated patients (PTPs) aged below 6 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED) in main study - Part A. | Previously treated patients (PTPs) aged 6 to 12 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED) in main study - Part A. | Previously untreated patients (PUPs) or minimally treated patients (MTPs, patients who had no more then 3 EDs with any FVIII product) received BAY81-8973 15-50 IU/kg at least 1x/week for 50 exposure days (ED) or until inhibitor development in main study - Part B. |
| Measure Participants | 25 | 26 | 43 |
| Median (Inter-Quartile Range) [Bleeds] |
1.88
(0.00)
|
0.00
(0.00)
|
0.0
(0.0)
|
| Title | Annualized Number of Total Bleeds During Prophylaxis Treatment |
|---|---|
| Description | Annualized number (mean +/- standard deviation) of total bleeds that occurred during prophylaxis treatment was summarized and reported. Total bleeds: sum of spontaneous bleeds, trauma bleeds (only treated bleeds were classified as spontaneous or trauma), untreated bleeds and 'other' bleeds ('other' bleeds were infusions with reason given as 'other'). |
| Time Frame | Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) analysis set - main study: all participants of the SAF in main study who had infusion/bleeding data from the electronic patient diary (EPD) |
| Arm/Group Title | Main Study - Part A: PTPs 0-<6 Years | Main Study - Part A: PTPs 6-12 Years | Main Study - Part B: PUPs/MTPs 0-<6 Years |
|---|---|---|---|
| Arm/Group Description | Previously treated patients (PTPs) aged below 6 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED) in main study - Part A. | Previously treated patients (PTPs) aged 6 to 12 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED) in main study - Part A. | Previously untreated patients (PUPs) or minimally treated patients (MTPs, patients who had no more then 3 EDs with any FVIII product) received BAY81-8973 15-50 IU/kg at least 1x/week for 50 exposure days (ED) or until inhibitor development in main study - Part B. |
| Measure Participants | 25 | 26 | 43 |
| Mean (Standard Deviation) [Bleeds] |
4.16
(5.02)
|
3.37
(5.01)
|
7.1
(8.6)
|
| Title | Annualized Number of Total Bleeds During Prophylaxis Treatment |
|---|---|
| Description | Annualized number (median [inter-quartile range (Q1-Q3)]) of total bleeds that occurred during prophylaxis treatment was summarized and reported. Total bleeds: sum of spontaneous bleeds, trauma bleeds (only treated bleeds were classified as spontaneous or trauma), untreated bleeds and 'other' bleeds ('other' bleeds were infusions with reason given as 'other'). |
| Time Frame | Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) analysis set - main study: all participants of the SAF in main study who had infusion/bleeding data from the electronic patient diary (EPD) |
| Arm/Group Title | Main Study - Part A: PTPs 0-<6 Years | Main Study - Part A: PTPs 6-12 Years | Main Study - Part B: PUPs/MTPs 0-<6 Years |
|---|---|---|---|
| Arm/Group Description | Previously treated patients (PTPs) aged below 6 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED) in main study - Part A. | Previously treated patients (PTPs) aged 6 to 12 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED) in main study - Part A. | Previously untreated patients (PUPs) or minimally treated patients (MTPs, patients who had no more then 3 EDs with any FVIII product) received BAY81-8973 15-50 IU/kg at least 1x/week for 50 exposure days (ED) or until inhibitor development in main study - Part B. |
| Measure Participants | 25 | 26 | 43 |
| Median (Inter-Quartile Range) [Bleeds] |
2.03
(0.00)
|
0.93
(0.00)
|
4.7
(2.1)
|
| Title | Hemostatic Control During Major and Minor Surgeries |
|---|---|
| Description | For participants who underwent major or minor surgeries during the study, hemostasis during the surgeries was assessed as excellent, good, moderate or poor. Number of surgeries per assessment was summarized and reported. |
| Time Frame | Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in SAF in main study who underwent major or minor surgeries during the study |
| Arm/Group Title | Main Study - Part A: PTPs 0-<6 Years | Main Study - Part A: PTPs 6-12 Years | Main Study - Part B: PUPs/MTPs 0-<6 Years |
|---|---|---|---|
| Arm/Group Description | Previously treated patients (PTPs) aged below 6 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED) in main study - Part A. | Previously treated patients (PTPs) aged 6 to 12 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED) in main study - Part A. | Previously untreated patients (PUPs) or minimally treated patients (MTPs, patients who had no more then 3 EDs with any FVIII product) received BAY81-8973 15-50 IU/kg at least 1x/week for 50 exposure days (ED) or until inhibitor development in main study - Part B. |
| Measure Participants | 0 | 1 | 6 |
| Measure Surgeries | 0 | 1 | 6 |
| Excellent |
0
|
0
|
3
|
| Good |
0
|
0
|
1
|
| Moderate |
0
|
0
|
0
|
| Poor |
0
|
0
|
0
|
| Not available |
0
|
0
|
1
|
| Excellent |
0
|
0
|
0
|
| Good |
0
|
1
|
1
|
| Moderate |
0
|
0
|
0
|
| Poor |
0
|
0
|
0
|
| Not available |
0
|
0
|
0
|
| Title | Number of Participants With Inhibitor Development in Main Study |
|---|---|
| Description | Number of participants with confirmed positive FVIII inhibitor titer (≥ 0.6 Bethesda unit [BU/mL]) during the main study was summarized and classified as participants developing low titer inhibitor (i.e. ≥ 0.6 to ≤ 5.0 BU/mL) and participants developing high titer inhibitor (i.e. > 5.0 BU/mL). |
| Time Frame | Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in main study - safety analysis set (SAF, all participants who entered Study Part A or Part B and received at least one infusion of study medication) with inhibitor measurements done |
| Arm/Group Title | Main Study - Part A: PTPs 0-<6 Years | Main Study - Part A: PTPs 6-12 Years | Main Study - Part B: PUPs/MTPs 0-<6 Years |
|---|---|---|---|
| Arm/Group Description | Previously treated patients (PTPs) aged below 6 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED) in main study - Part A. | Previously treated patients (PTPs) aged 6 to 12 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED) in main study - Part A. | Previously untreated patients (PUPs) or minimally treated patients (MTPs, patients who had no more then 3 EDs with any FVIII product) received BAY81-8973 15-50 IU/kg at least 1x/week for 50 exposure days (ED) or until inhibitor development in main study - Part B. |
| Measure Participants | 25 | 26 | 42 |
| Low titer inhibitor |
0
0%
|
0
0%
|
6
14%
|
| High titer inhibitor |
0
0%
|
0
0%
|
17
39.5%
|
| Title | Number of Participants With New Inhibitor Development in Extension Study |
|---|---|
| Description | Number of participants who had not developed an inhibitor during the main study but developed an inhibitor (confirmed positive FVIII inhibitor titer [≥ 0.6 BU/mL]) during the extension study was summarized and classified as participants developing low titer inhibitor (i.e. ≥ 0.6 to ≤ 5.0 BU/mL) and participants developing high titer inhibitor (i.e. > 5.0 BU/mL). |
| Time Frame | From start of extension study to at least 100 cumulative exposure days (EDs) (median 421 EDs; median 3.8 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who entered the extension study and had not developed inhibitors during the main study Part A or Part B |
| Arm/Group Title | Extension Study - Former Part A Participants | Extension Study - Former Part B Participants |
|---|---|---|
| Arm/Group Description | Participants having reached at least 50 exposure days (EDs) in main study - Part A were offered participation in an open label extension study (optional). Participants who transitioned from main study - Part A to the extension study received BAY81-8973, 25-50 IU/kg at least 2x/week for at least 100 cumulative EDs (main study - Part A and extension study). | Participants having reached at least 50 exposure days (EDs) in main study - Part B were offered participation in an open label extension study and received BAY81-8973 25-50 IU/kg at least 2x/week for at least 100 cumulative EDs (main study - Part B and extension study); participants who developed an inhibitor in main study - Part B were offered participation in open label extension study and received Immune Tolerance Induction (ITI) treatment with BAY81-8973 until successful eradication of the inhibitor, or until failure, for approximately 18 months. |
| Measure Participants | 46 | 16 |
| Low titer inhibitor (incl. false-positive) |
1
4%
|
0
0%
|
| High titer inhibitor |
0
0%
|
0
0%
|
| Title | Factor VIII Recovery Values |
|---|---|
| Description | Incremental recovery of Factor VIII (FVIII) at 20-30 min after end of infusions was determined and mean recovery values were reported. |
| Time Frame | Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in intent-to-treat (ITT) analysis set in main study with valid FVIII recovery values |
| Arm/Group Title | Main Study - Part A: PTPs 0-<6 Years | Main Study - Part A: PTPs 6-12 Years | Main Study - Part B: PUPs/MTPs 0-<6 Years |
|---|---|---|---|
| Arm/Group Description | Previously treated patients (PTPs) aged below 6 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED) in main study - Part A. | Previously treated patients (PTPs) aged 6 to 12 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED) in main study - Part A. | Previously untreated patients (PUPs) or minimally treated patients (MTPs, patients who had no more then 3 EDs with any FVIII product) received BAY81-8973 15-50 IU/kg at least 1x/week for 50 exposure days (ED) or until inhibitor development in main study - Part B. |
| Measure Participants | 25 | 26 | 32 |
| Participants without inhibitor |
1.63
(0.31)
|
1.72
(0.46)
|
1.76
(0.55)
|
| Participants with low titer inhibitor |
0.86
(0.56)
|
||
| Participants with high titer inhibitor |
0.38
(0.42)
|
| Title | Consumption of Factor VIII in All Infusions |
|---|---|
| Description | Factor VIII (FVIII) usage/consumption was summarized for all infusions. Consumption per participant's body weight per year was calculated and reported. |
| Time Frame | Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) analysis set - main study: all participants of the SAF in main study who had infusion/bleeding data from the electronic patient diary (EPD) |
| Arm/Group Title | Main Study - Part A: PTPs 0-<6 Years | Main Study - Part A: PTPs 6-12 Years | Main Study - Part B: PUPs/MTPs 0-<6 Years |
|---|---|---|---|
| Arm/Group Description | Previously treated patients (PTPs) aged below 6 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED) in main study - Part A. | Previously treated patients (PTPs) aged 6 to 12 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED) in main study - Part A. | Previously untreated patients (PUPs) or minimally treated patients (MTPs, patients who had no more then 3 EDs with any FVIII product) received BAY81-8973 15-50 IU/kg at least 1x/week for 50 exposure days (ED) or until inhibitor development in main study - Part B. |
| Measure Participants | 25 | 26 | 43 |
| Mean (Standard Deviation) [international units/kilogram/year] |
5499.1
(1996.2)
|
4679.1
(1688.7)
|
2195.8
(1903.6)
|
| Title | Consumption of FVIII in Infusions for Prophylaxis |
|---|---|
| Description | Factor VIII (FVIII) usage/consumption was summarized for prophylaxis infusions. Consumption per participant's body weight per year was calculated and reported. |
| Time Frame | Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in intent-to-treat (ITT) analysis set in main study with at least one dose of prophylaxis treatment with study drug |
| Arm/Group Title | Main Study - Part A: PTPs 0-<6 Years | Main Study - Part A: PTPs 6-12 Years | Main Study - Part B: PUPs/MTPs 0-<6 Years |
|---|---|---|---|
| Arm/Group Description | Previously treated patients (PTPs) aged below 6 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED) in main study - Part A. | Previously treated patients (PTPs) aged 6 to 12 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED) in main study - Part A. | Previously untreated patients (PUPs) or minimally treated patients (MTPs, patients who had no more then 3 EDs with any FVIII product) received BAY81-8973 15-50 IU/kg at least 1x/week for 50 exposure days (ED) or until inhibitor development in main study - Part B. |
| Measure Participants | 25 | 26 | 42 |
| Mean (Standard Deviation) [international units/kilogram/year] |
5224.8
(1760.2)
|
4492.7
(1667.6)
|
1486.6
(963.3)
|
| Title | Consumption of FVIII in Infusions for the Treatment of Bleeds |
|---|---|
| Description | Factor VIII (FVIII) usage/consumption was summarized for infusions used to treat breakthrough bleeds. Consumption per participant's body weight per year was calculated and reported. |
| Time Frame | Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in intent-to-treat (ITT) analysis set in main study with at least one bleed treated with study drug |
| Arm/Group Title | Main Study - Part A: PTPs 0-<6 Years | Main Study - Part A: PTPs 6-12 Years | Main Study - Part B: PUPs/MTPs 0-<6 Years |
|---|---|---|---|
| Arm/Group Description | Previously treated patients (PTPs) aged below 6 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED) in main study - Part A. | Previously treated patients (PTPs) aged 6 to 12 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED) in main study - Part A. | Previously untreated patients (PUPs) or minimally treated patients (MTPs, patients who had no more then 3 EDs with any FVIII product) received BAY81-8973 15-50 IU/kg at least 1x/week for 50 exposure days (ED) or until inhibitor development in main study - Part B. |
| Measure Participants | 15 | 11 | 35 |
| Mean (Standard Deviation) [international units/kilogram/year] |
457.07
(526.87)
|
391.64
(219.61)
|
835.4
(1926.4)
|
| Title | Number of Infusions Per Bleed |
|---|---|
| Description | The number of infusions used to treat a bleed was defined as the first infusion to treat the bleed plus all follow-up infusions to treat the same bleed, if any. The mean value of number of infusions for each bleed was calculated and reported. |
| Time Frame | Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in intent-to-treat (ITT) analysis set in main study with at least one bleed |
| Arm/Group Title | Main Study - Part A: PTPs 0-<6 Years | Main Study - Part A: PTPs 6-12 Years | Main Study - Part B: PUPs/MTPs 0-<6 Years |
|---|---|---|---|
| Arm/Group Description | Previously treated patients (PTPs) aged below 6 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED) in main study - Part A. | Previously treated patients (PTPs) aged 6 to 12 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED) in main study - Part A. | Previously untreated patients (PUPs) or minimally treated patients (MTPs, patients who had no more then 3 EDs with any FVIII product) received BAY81-8973 15-50 IU/kg at least 1x/week for 50 exposure days (ED) or until inhibitor development in main study - Part B. |
| Measure Participants | 15 | 13 | 37 |
| Mean (Standard Deviation) [Infusions] |
1.3
(1.8)
|
1.4
(1.7)
|
1.7
(8.7)
|
| Title | Response to Treatment of Bleeds |
|---|---|
| Description | Participants or caregivers were asked to assess the response to treatment of bleeds as excellent, good, moderate or poor. Percentage of bleeds per assessment was summarized and reported. |
| Time Frame | Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in intent-to-treat (ITT) analysis set in main study with at least one bleed |
| Arm/Group Title | Main Study - Part A: PTPs 0-<6 Years | Main Study - Part A: PTPs 6-12 Years | Main Study - Part B: PUPs/MTPs 0-<6 Years |
|---|---|---|---|
| Arm/Group Description | Previously treated patients (PTPs) aged below 6 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED) in main study - Part A. | Previously treated patients (PTPs) aged 6 to 12 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED) in main study - Part A. | Previously untreated patients (PUPs) or minimally treated patients (MTPs, patients who had no more then 3 EDs with any FVIII product) received BAY81-8973 15-50 IU/kg at least 1x/week for 50 exposure days (ED) or until inhibitor development in main study - Part B. |
| Measure Participants | 15 | 13 | 37 |
| Measure Bleeds assessed for the response | 44 | 37 | 105 |
| Excellent |
20
|
12
|
27
|
| Good |
23
|
18
|
56
|
| Moderate |
0
|
7
|
16
|
| Poor |
1
|
0
|
6
|
| Title | Half-life (t1/2) of BAY81-8973 in Plasma |
|---|---|
| Description | Half-life (t1/2) of BAY81-8973 in plasma was measured. Geometric mean and percentage geometric coefficient of variation (%CV) were reported. |
| Time Frame | Pre-infusion and until 24 hours post infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in PK analysis set (PKS) - A with evaluable data for this endpoint (PKS - A: all participants who entered main study - Part A and received at least one infusion of study medication with evaluable pharmacokinetic data) |
| Arm/Group Title | Main Study - Part A: PTPs 0-<6 Years | Main Study - Part A: PTPs 6-12 Years |
|---|---|---|
| Arm/Group Description | Previously treated patients (PTPs) aged below 6 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED) in main study - Part A. | Previously treated patients (PTPs) aged 6 to 12 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED) in main study - Part A. |
| Measure Participants | 2 | 9 |
| Geometric Mean (Geometric Coefficient of Variation) [Hours] |
13.2
(39.7)
|
12.1
(16.3)
|
Adverse Events
| Time Frame | Main study - Part A: from the first BAY81-8973 infusion until 3 days after the last infusion (median 6 months); Main study - Part B: from the first BAY81-8973 infusion until 7 days after the last infusion (median 8 months); Extension: from start of extension study until 3 days after the last infusion in extension study (median 3.1 years) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||
| Arm/Group Title | Main Study - Part A: PTPs 0-<6 Years | Main Study - Part A: PTPs 6-12 Years | Main Study - Part B: PUPs/MTPs 0-<6 Years | Extension Study - Former Part A Participants | Extension Study - Former Part B Participants | |||||
| Arm/Group Description | Previously treated patients (PTPs) aged below 6 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED) in main study - Part A. | Previously treated patients (PTPs) aged 6 to 12 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED) in main study - Part A. | Previously untreated patients (PUPs) or minimally treated patients (MTPs, patients who had no more then 3 exposure days (EDs) with any FVIII product) received BAY81-8973 15-50 IU/kg at least 1x/week for 50 EDs or until inhibitor development in main study - Part B. | Participants having reached at least 50 exposure days (EDs) in main study - Part A were offered participation in an open label extension study (optional). Participants who transitioned from main study - Part A to the extension study received BAY81-8973, 25-50 IU/kg at least 2x/week for at least 100 cumulative EDs (main study - Part A and extension study). | Participants having reached at least 50 exposure days (EDs) in main study - Part B were offered participation in an open label extension study and received BAY81-8973 25-50 IU/kg at least 2x/week for at least 100 cumulative EDs (main study - Part B and extension study); participants who developed an inhibitor in main study - Part B were offered participation in open label extension study and received Immune Tolerance Induction (ITI) treatment with BAY81-8973 until successful eradication of the inhibitor, or until failure, for approximately 18 months. | |||||
All Cause Mortality |
||||||||||
| Main Study - Part A: PTPs 0-<6 Years | Main Study - Part A: PTPs 6-12 Years | Main Study - Part B: PUPs/MTPs 0-<6 Years | Extension Study - Former Part A Participants | Extension Study - Former Part B Participants | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/25 (0%) | 0/26 (0%) | 0/43 (0%) | 0/46 (0%) | 0/36 (0%) | |||||
Serious Adverse Events |
||||||||||
| Main Study - Part A: PTPs 0-<6 Years | Main Study - Part A: PTPs 6-12 Years | Main Study - Part B: PUPs/MTPs 0-<6 Years | Extension Study - Former Part A Participants | Extension Study - Former Part B Participants | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/25 (0%) | 5/26 (19.2%) | 26/43 (60.5%) | 23/46 (50%) | 14/36 (38.9%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Blood loss anaemia | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 2/36 (5.6%) | 3 |
| Factor VIII inhibition | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 1/43 (2.3%) | 1 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Thrombocytopenia | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 1/46 (2.2%) | 1 | 0/36 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||
| Abdominal pain | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 1/46 (2.2%) | 3 | 0/36 (0%) | 0 |
| Gastritis | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 1/46 (2.2%) | 1 | 0/36 (0%) | 0 |
| Gastritis haemorrhagic | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 1/46 (2.2%) | 1 | 0/36 (0%) | 0 |
| Gastrointestinal haemorrhage | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 1/36 (2.8%) | 1 |
| Mouth haemorrhage | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 1/36 (2.8%) | 2 |
| Vomiting | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 1/43 (2.3%) | 1 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| General disorders | ||||||||||
| Catheter site granuloma | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 1/36 (2.8%) | 1 |
| Catheter site haematoma | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 1/43 (2.3%) | 1 | 0/46 (0%) | 0 | 1/36 (2.8%) | 1 |
| Catheter site haemorrhage | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 2/36 (5.6%) | 2 |
| Catheter site related reaction | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 1/36 (2.8%) | 1 |
| Decreased activity | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 1/43 (2.3%) | 1 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Extravasation | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 1/43 (2.3%) | 1 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Facial pain | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 1/43 (2.3%) | 1 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Pyrexia | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 1/43 (2.3%) | 1 | 1/46 (2.2%) | 1 | 0/36 (0%) | 0 |
| Infections and infestations | ||||||||||
| Appendicitis | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 1/46 (2.2%) | 1 | 0/36 (0%) | 0 |
| Bacteraemia | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 1/36 (2.8%) | 1 |
| Bacterial infection | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Bronchitis | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 1/46 (2.2%) | 1 | 0/36 (0%) | 0 |
| Cellulitis | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 1/46 (2.2%) | 1 | 0/36 (0%) | 0 |
| Cellulitis orbital | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 1/36 (2.8%) | 1 |
| Enterococcal sepsis | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 1/36 (2.8%) | 1 |
| Epidemic pleurodynia | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 1/46 (2.2%) | 1 | 0/36 (0%) | 0 |
| Escherichia urinary tract infection | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 1/43 (2.3%) | 1 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Gastroenteritis | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 1/36 (2.8%) | 1 |
| Gastroenteritis rotavirus | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 2/36 (5.6%) | 2 |
| Gastroenteritis staphylococcal | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 1/43 (2.3%) | 1 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Gastroenteritis viral | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 1/43 (2.3%) | 1 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Nasopharyngitis | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 1/46 (2.2%) | 1 | 0/36 (0%) | 0 |
| Otitis media acute | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 1/36 (2.8%) | 1 |
| Peritonsillar abscess | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 1/46 (2.2%) | 1 | 0/36 (0%) | 0 |
| Pneumonia | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 1/46 (2.2%) | 1 | 0/36 (0%) | 0 |
| Pulpitis dental | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 1/46 (2.2%) | 1 | 0/36 (0%) | 0 |
| Respiratory tract infection | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 1/46 (2.2%) | 1 | 0/36 (0%) | 0 |
| Sepsis | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 1/36 (2.8%) | 1 |
| Tonsillitis | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 1/46 (2.2%) | 1 | 0/36 (0%) | 0 |
| Tooth abscess | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Tracheitis | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 1/46 (2.2%) | 2 | 0/36 (0%) | 0 |
| Upper respiratory tract infection | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 1/36 (2.8%) | 1 |
| Vascular device infection | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 2/46 (4.3%) | 3 | 3/36 (8.3%) | 4 |
| Viral infection | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 0/43 (0%) | 0 | 1/46 (2.2%) | 1 | 0/36 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||
| Craniocerebral injury | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 1/43 (2.3%) | 1 | 0/46 (0%) | 0 | 1/36 (2.8%) | 1 |
| Injury | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 1/46 (2.2%) | 1 | 0/36 (0%) | 0 |
| Mouth injury | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 1/43 (2.3%) | 1 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Post procedural haemorrhage | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 1/36 (2.8%) | 1 |
| Radius fracture | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 2/46 (4.3%) | 2 | 0/36 (0%) | 0 |
| Subcutaneous haematoma | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 1/36 (2.8%) | 1 |
| Subdural haematoma | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 1/36 (2.8%) | 1 |
| Traumatic haemorrhage | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 1/36 (2.8%) | 1 |
| Traumatic haemothorax | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 1/36 (2.8%) | 1 |
| Ulna fracture | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 1/46 (2.2%) | 1 | 0/36 (0%) | 0 |
| Investigations | ||||||||||
| Anti factor VIII antibody positive | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 22/43 (51.2%) | 24 | 1/46 (2.2%) | 1 | 0/36 (0%) | 0 |
| Catheterisation cardiac | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 1/36 (2.8%) | 1 |
| Electroencephalogram abnormal | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 1/46 (2.2%) | 1 | 0/36 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||
| Dehydration | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 1/36 (2.8%) | 1 |
| Metabolic syndrome | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 1/46 (2.2%) | 1 | 0/36 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||
| Arthritis reactive | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 1/46 (2.2%) | 1 | 0/36 (0%) | 0 |
| Haemarthrosis | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 3/43 (7%) | 5 | 1/46 (2.2%) | 1 | 3/36 (8.3%) | 3 |
| Haematoma muscle | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 1/43 (2.3%) | 1 | 1/46 (2.2%) | 1 | 1/36 (2.8%) | 1 |
| Soft tissue haemorrhage | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 2/43 (4.7%) | 2 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Nervous system disorders | ||||||||||
| Cerebral haemorrhage | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 1/43 (2.3%) | 1 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Encephalomalacia | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Multiple sclerosis | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 1/46 (2.2%) | 1 | 0/36 (0%) | 0 |
| Subarachnoid haemorrhage | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 1/36 (2.8%) | 1 |
| Product Issues | ||||||||||
| Device failure | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 1/46 (2.2%) | 1 | 1/36 (2.8%) | 1 |
| Device occlusion | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 1/46 (2.2%) | 1 | 0/36 (0%) | 0 |
| Internal device exposed | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 1/36 (2.8%) | 1 |
| Renal and urinary disorders | ||||||||||
| Haematuria | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 1/46 (2.2%) | 1 | 0/36 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Epistaxis | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 1/36 (2.8%) | 1 |
| Laryngeal haematoma | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 1/46 (2.2%) | 1 | 0/36 (0%) | 0 |
| Nasal polyps | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 1/46 (2.2%) | 1 | 0/36 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||
| Drug eruption | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 1/46 (2.2%) | 1 | 0/36 (0%) | 0 |
| Surgical and medical procedures | ||||||||||
| Adenotonsillectomy | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 1/46 (2.2%) | 1 | 0/36 (0%) | 0 |
| Central venous catheter removal | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 1/46 (2.2%) | 1 | 2/36 (5.6%) | 2 |
| Central venous catheterisation | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 1/43 (2.3%) | 1 | 2/46 (4.3%) | 2 | 4/36 (11.1%) | 4 |
| Dental cleaning | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Immune tolerance induction | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 2/36 (5.6%) | 3 |
| Tooth extraction | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 1/46 (2.2%) | 1 | 0/36 (0%) | 0 |
| Vascular disorders | ||||||||||
| Haematoma | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 1/43 (2.3%) | 1 | 0/46 (0%) | 0 | 1/36 (2.8%) | 2 |
Other (Not Including Serious) Adverse Events |
||||||||||
| Main Study - Part A: PTPs 0-<6 Years | Main Study - Part A: PTPs 6-12 Years | Main Study - Part B: PUPs/MTPs 0-<6 Years | Extension Study - Former Part A Participants | Extension Study - Former Part B Participants | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 16/25 (64%) | 19/26 (73.1%) | 28/43 (65.1%) | 41/46 (89.1%) | 24/36 (66.7%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Anaemia | 0/25 (0%) | 0 | 1/26 (3.8%) | 3 | 3/43 (7%) | 3 | 0/46 (0%) | 0 | 3/36 (8.3%) | 10 |
| Blood loss anaemia | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 2/43 (4.7%) | 2 | 1/46 (2.2%) | 1 | 0/36 (0%) | 0 |
| Iron deficiency anaemia | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 1/43 (2.3%) | 1 | 1/46 (2.2%) | 5 | 2/36 (5.6%) | 2 |
| Congenital, familial and genetic disorders | ||||||||||
| Phimosis | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 2/46 (4.3%) | 3 | 0/36 (0%) | 0 |
| Ear and labyrinth disorders | ||||||||||
| Ear pain | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 1/43 (2.3%) | 1 | 0/46 (0%) | 0 | 2/36 (5.6%) | 2 |
| Eye disorders | ||||||||||
| Conjunctivitis allergic | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Photophobia | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Strabismus | 0/25 (0%) | 0 | 1/26 (3.8%) | 3 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||
| Abdominal pain | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 0/43 (0%) | 0 | 5/46 (10.9%) | 5 | 0/36 (0%) | 0 |
| Abdominal pain upper | 1/25 (4%) | 1 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 5/46 (10.9%) | 5 | 0/36 (0%) | 0 |
| Constipation | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 1/43 (2.3%) | 1 | 1/46 (2.2%) | 1 | 1/36 (2.8%) | 1 |
| Dental caries | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 0/43 (0%) | 0 | 1/46 (2.2%) | 2 | 0/36 (0%) | 0 |
| Diarrhoea | 2/25 (8%) | 3 | 1/26 (3.8%) | 2 | 6/43 (14%) | 8 | 5/46 (10.9%) | 5 | 1/36 (2.8%) | 1 |
| Functional gastrointestinal disorder | 0/25 (0%) | 0 | 1/26 (3.8%) | 2 | 1/43 (2.3%) | 1 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Glossodynia | 1/25 (4%) | 1 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Haematochezia | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Nausea | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 3/46 (6.5%) | 4 | 0/36 (0%) | 0 |
| Stomatitis | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 2/36 (5.6%) | 2 |
| Teething | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 2/43 (4.7%) | 3 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Toothache | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 0/43 (0%) | 0 | 2/46 (4.3%) | 3 | 1/36 (2.8%) | 1 |
| Vomiting | 1/25 (4%) | 1 | 1/26 (3.8%) | 1 | 4/43 (9.3%) | 8 | 4/46 (8.7%) | 4 | 6/36 (16.7%) | 10 |
| General disorders | ||||||||||
| Catheter site haematoma | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 2/36 (5.6%) | 3 |
| Fatigue | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Hyperthermia | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Infusion site swelling | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Injection site bruising | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Oedema peripheral | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 2/46 (4.3%) | 2 | 0/36 (0%) | 0 |
| Peripheral swelling | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 0/43 (0%) | 0 | 3/46 (6.5%) | 4 | 0/36 (0%) | 0 |
| Pyrexia | 5/25 (20%) | 10 | 2/26 (7.7%) | 2 | 12/43 (27.9%) | 19 | 8/46 (17.4%) | 19 | 11/36 (30.6%) | 21 |
| Immune system disorders | ||||||||||
| Hypersensitivity | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Infections and infestations | ||||||||||
| Bronchiolitis | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 2/43 (4.7%) | 4 | 1/46 (2.2%) | 2 | 1/36 (2.8%) | 1 |
| Bronchitis | 1/25 (4%) | 1 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 2/46 (4.3%) | 4 | 3/36 (8.3%) | 5 |
| Catheter site infection | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 2/36 (5.6%) | 2 |
| Conjunctivitis | 2/25 (8%) | 2 | 0/26 (0%) | 0 | 3/43 (7%) | 3 | 3/46 (6.5%) | 4 | 2/36 (5.6%) | 3 |
| Cystitis | 1/25 (4%) | 1 | 0/26 (0%) | 0 | 1/43 (2.3%) | 1 | 0/46 (0%) | 0 | 1/36 (2.8%) | 1 |
| Dysentery | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 2/36 (5.6%) | 4 |
| Ear infection | 1/25 (4%) | 1 | 0/26 (0%) | 0 | 2/43 (4.7%) | 2 | 4/46 (8.7%) | 4 | 1/36 (2.8%) | 4 |
| Enterovirus infection | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 2/36 (5.6%) | 2 |
| Gastroenteritis | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 1/43 (2.3%) | 1 | 1/46 (2.2%) | 1 | 3/36 (8.3%) | 5 |
| Gastroenteritis viral | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 3/43 (7%) | 3 | 2/46 (4.3%) | 3 | 0/36 (0%) | 0 |
| Gastrointestinal viral infection | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Hand-foot-and-mouth disease | 1/25 (4%) | 1 | 0/26 (0%) | 0 | 1/43 (2.3%) | 1 | 0/46 (0%) | 0 | 1/36 (2.8%) | 1 |
| Hookworm infection | 1/25 (4%) | 1 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 1/46 (2.2%) | 1 | 0/36 (0%) | 0 |
| Influenza | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 4/43 (9.3%) | 4 | 2/46 (4.3%) | 2 | 1/36 (2.8%) | 1 |
| Laryngitis | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 1/43 (2.3%) | 1 | 1/46 (2.2%) | 1 | 3/36 (8.3%) | 4 |
| Nasopharyngitis | 2/25 (8%) | 3 | 2/26 (7.7%) | 2 | 6/43 (14%) | 16 | 13/46 (28.3%) | 31 | 9/36 (25%) | 23 |
| Oral herpes | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 1/43 (2.3%) | 1 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Otitis media | 1/25 (4%) | 1 | 0/26 (0%) | 0 | 1/43 (2.3%) | 3 | 0/46 (0%) | 0 | 2/36 (5.6%) | 3 |
| Otitis media acute | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 1/43 (2.3%) | 1 | 0/46 (0%) | 0 | 1/36 (2.8%) | 2 |
| Pharyngitis | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 3/46 (6.5%) | 3 | 1/36 (2.8%) | 1 |
| Pharyngitis streptococcal | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 2/46 (4.3%) | 2 | 0/36 (0%) | 0 |
| Pneumonia | 1/25 (4%) | 1 | 0/26 (0%) | 0 | 1/43 (2.3%) | 1 | 4/46 (8.7%) | 4 | 0/36 (0%) | 0 |
| Respiratory tract infection | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 1/43 (2.3%) | 1 | 5/46 (10.9%) | 10 | 0/36 (0%) | 0 |
| Rhinitis | 1/25 (4%) | 1 | 1/26 (3.8%) | 1 | 3/43 (7%) | 4 | 6/46 (13%) | 8 | 1/36 (2.8%) | 3 |
| Tonsillitis | 1/25 (4%) | 2 | 1/26 (3.8%) | 1 | 1/43 (2.3%) | 1 | 10/46 (21.7%) | 25 | 0/36 (0%) | 0 |
| Tooth abscess | 1/25 (4%) | 1 | 1/26 (3.8%) | 2 | 0/43 (0%) | 0 | 2/46 (4.3%) | 2 | 0/36 (0%) | 0 |
| Tracheitis | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 1/43 (2.3%) | 1 | 0/46 (0%) | 0 | 1/36 (2.8%) | 1 |
| Upper respiratory tract infection | 1/25 (4%) | 1 | 1/26 (3.8%) | 2 | 3/43 (7%) | 3 | 6/46 (13%) | 11 | 2/36 (5.6%) | 2 |
| Varicella | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 1/43 (2.3%) | 1 | 2/46 (4.3%) | 2 | 4/36 (11.1%) | 4 |
| Vascular device infection | 1/25 (4%) | 1 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 1/46 (2.2%) | 2 | 1/36 (2.8%) | 2 |
| Viral infection | 3/25 (12%) | 3 | 2/26 (7.7%) | 2 | 1/43 (2.3%) | 1 | 6/46 (13%) | 15 | 2/36 (5.6%) | 4 |
| Viral upper respiratory tract infection | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 0/43 (0%) | 0 | 1/46 (2.2%) | 2 | 0/36 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||
| Contusion | 2/25 (8%) | 3 | 0/26 (0%) | 0 | 1/43 (2.3%) | 1 | 2/46 (4.3%) | 2 | 0/36 (0%) | 0 |
| Eye contusion | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 2/46 (4.3%) | 2 | 1/36 (2.8%) | 1 |
| Face injury | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 2/43 (4.7%) | 2 | 0/46 (0%) | 0 | 1/36 (2.8%) | 1 |
| Fall | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 2/43 (4.7%) | 2 | 2/46 (4.3%) | 2 | 0/36 (0%) | 0 |
| Genital contusion | 1/25 (4%) | 1 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Head injury | 1/25 (4%) | 1 | 0/26 (0%) | 0 | 1/43 (2.3%) | 1 | 1/46 (2.2%) | 1 | 4/36 (11.1%) | 4 |
| Joint injury | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 2/46 (4.3%) | 3 | 0/36 (0%) | 0 |
| Limb injury | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 0/43 (0%) | 0 | 9/46 (19.6%) | 11 | 1/36 (2.8%) | 1 |
| Lip injury | 1/25 (4%) | 1 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Procedural pain | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 3/46 (6.5%) | 3 | 0/36 (0%) | 0 |
| Road traffic accident | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Skin abrasion | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Skin injury | 1/25 (4%) | 1 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Skin laceration | 1/25 (4%) | 1 | 0/26 (0%) | 0 | 1/43 (2.3%) | 1 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Subcutaneous haematoma | 1/25 (4%) | 1 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 1/36 (2.8%) | 1 |
| Tongue injury | 1/25 (4%) | 1 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Ulna fracture | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 2/46 (4.3%) | 2 | 0/36 (0%) | 0 |
| Investigations | ||||||||||
| Haemoglobin decreased | 1/25 (4%) | 1 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Neutrophil count increased | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| White blood cell count increased | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||
| Dehydration | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Iron deficiency | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 2/36 (5.6%) | 3 |
| Musculoskeletal and connective tissue disorders | ||||||||||
| Arthralgia | 0/25 (0%) | 0 | 2/26 (7.7%) | 2 | 0/43 (0%) | 0 | 6/46 (13%) | 9 | 0/36 (0%) | 0 |
| Back pain | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 2/46 (4.3%) | 2 | 0/36 (0%) | 0 |
| Groin pain | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 2/46 (4.3%) | 2 | 0/36 (0%) | 0 |
| Joint swelling | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Pain in extremity | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 1/43 (2.3%) | 1 | 4/46 (8.7%) | 6 | 0/36 (0%) | 0 |
| Synovitis | 1/25 (4%) | 1 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 1/46 (2.2%) | 1 | 0/36 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Skin papilloma | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 2/46 (4.3%) | 2 | 0/36 (0%) | 0 |
| Nervous system disorders | ||||||||||
| Headache | 2/25 (8%) | 3 | 4/26 (15.4%) | 4 | 0/43 (0%) | 0 | 8/46 (17.4%) | 23 | 0/36 (0%) | 0 |
| Product Issues | ||||||||||
| Device failure | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 3/46 (6.5%) | 3 | 0/36 (0%) | 0 |
| Psychiatric disorders | ||||||||||
| Attention deficit hyperactivity disorder | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 2/46 (4.3%) | 2 | 0/36 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||||
| Perineal pain | 0/25 (0%) | 0 | 1/26 (3.8%) | 1 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Adenoidal hypertrophy | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 2/46 (4.3%) | 2 | 0/36 (0%) | 0 |
| Asthma | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 1/43 (2.3%) | 1 | 2/46 (4.3%) | 3 | 0/36 (0%) | 0 |
| Cough | 2/25 (8%) | 4 | 4/26 (15.4%) | 4 | 1/43 (2.3%) | 1 | 9/46 (19.6%) | 18 | 3/36 (8.3%) | 6 |
| Epistaxis | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 2/46 (4.3%) | 6 | 0/36 (0%) | 0 |
| Oropharyngeal pain | 0/25 (0%) | 0 | 2/26 (7.7%) | 3 | 0/43 (0%) | 0 | 5/46 (10.9%) | 8 | 0/36 (0%) | 0 |
| Productive cough | 2/25 (8%) | 3 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 1/46 (2.2%) | 1 | 0/36 (0%) | 0 |
| Rhinitis allergic | 1/25 (4%) | 1 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 3/46 (6.5%) | 3 | 0/36 (0%) | 0 |
| Rhinorrhoea | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 2/46 (4.3%) | 4 | 0/36 (0%) | 0 |
| Tonsillar hypertrophy | 1/25 (4%) | 1 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Increased upper airway secretion | 1/25 (4%) | 1 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||
| Dermatitis atopic | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 2/36 (5.6%) | 2 |
| Ecchymosis | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 2/46 (4.3%) | 3 | 0/36 (0%) | 0 |
| Pruritus | 3/25 (12%) | 3 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 0/46 (0%) | 0 | 0/36 (0%) | 0 |
| Rash | 0/25 (0%) | 0 | 2/26 (7.7%) | 3 | 3/43 (7%) | 3 | 3/46 (6.5%) | 3 | 1/36 (2.8%) | 3 |
| Surgical and medical procedures | ||||||||||
| Central venous catheter removal | 0/25 (0%) | 0 | 0/26 (0%) | 0 | 0/43 (0%) | 0 | 2/46 (4.3%) | 2 | 0/36 (0%) | 0 |
| Tooth extraction | 0/25 (0%) | 0 | 2/26 (7.7%) | 3 | 0/43 (0%) | 0 | 2/46 (4.3%) | 5 | 0/36 (0%) | 0 |
Limitations/Caveats
Due to the small number of participants per reporting group, all presented summary measures (e.g. mean and proportion) have to be evaluated with caution. If displayed standard deviation should be taken into account. The participant who had a low titer inhibitor detected after 549 EDs during the extension study was considered to have a false positive result due to cross reactivity with IgG anticardiolipin antibodies.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The sponsor can review results communications prior to public release and can embargo communications regarding trial results within 60 days. The sponsor can require changes to the communication for any patentable subject matter or termed confidential information. The PI cannot publish the results prior the first multicenter publication. If there is no multicenter publication within 18 months after the trial completion the PI has the right to publish the results from the PI site
Results Point of Contact
| Name/Title | Therapeutic Area Head |
|---|---|
| Organization | Bayer |
| Phone | 1-888-8422937 |
| clinical-trials-contact@bayer.com |
Responsible Party:
Bayer
ClinicalTrials.gov Identifier:
NCT01311648
Other Study ID Numbers:
- 13400
- 2010-021781-29
First Posted:
Mar 9, 2011
Last Update Posted:
Nov 17, 2021
Last Verified:
Nov 1, 2021