Blood Coagulation Disorders, Hemophilia A
Conditions
Keywords
Hemophilia A, Factor VIII, Prophylaxis
Brief summary
The study will assess the pharmacokinetics (part A) safety, tolerability, and efficacy of prophylaxis treatment (2 to 3 times a week) (part B) with BAY81-8973 over a one year period (split into two six month treatment periods). The study will compare 2 different methods (assays) for measuring the amount of study drug, the chromogenic substrate assay per European Pharmacopeia (CS/EP) with the classical assay (Chromogenic Substrate Adjusted, CS/ADJ). During one six month period patients will receive the study drug where the dose has been measured using the (CS/EP) and during the other six months period the dose will be measured based on the Chromogenic Substrate Adjusted assay CS/ADJ)
Interventions
BIOLOGICALRecombinant Factor VIII (BAY81-8973)
Single dose of BAY81-8973 crossed over to single dose of Kogenate FS
Single dose of Kogenate FS crossed over to Single dose of BAY81-8973
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
12 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male, aged 12 to 65 years * Severe hemophilia A defined as \< 1% FVIII:C * \>/= 150 days of previous treatment with FVIII in lifetime * Currently receiving on-demand or any type of prophylaxis treatment regimen with any FVIII product * No history of or current FVIII inhibitors
Exclusion criteria
* Presence of another bleeding disease that is different from hemophilia A (e.g., von Willebrand disease, hemophilia B) * Low platelet count, abnormal kidney function, or liver disease * Received treatment with immune suppressing drugs within the last 3 months prior or requires treatment during the study. (Some drugs for hepatitis C, Human immunodeficiency virus (HIV), and steroids are allowed) * Receiving or has received other experimental drugs within 3 months prior to study entry * Allergy to Factor VIII or hamsters or mouse protein
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A - Area Under the Drug Concentration-time Curve (AUC) | Samples taken at pre-injection, and at 0.25, 0.5, 1, 3, 6, 8, 24, 30 and 48 hours post injection. AUC calculated from time of injection to infinity. | To examine the Pharmacokinetic (PK) characteristics of BAY 81-8973 and ensure that the new drug is similar to Kogenate FS. All results are based on the chromogenic assay. |
| Part A - Half-life (t 1/2) | Samples taken at pre-injection, and at 0.25, 0.5, 1, 3, 6, 8, 24, 30 and 48 hours post injection. | To examine the PK characteristics of BAY81-8973 and ensure that the new drug is similar to Kogenate FS. All results are based on the chromogenic assay. |
| Part B - Annualized Number of Total Bleeds | 12 months after randomization | The annualized number of bleeds experienced by participants |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part B - Changes From Baseline at 12 Months in Quality of Life (QoL) as Measured by Transformed Total Score of Haemo-QoL Questionnaire | Baseline and 12 months | A measure of how treatment with BAY81-8973 affected the daily life of participants. the scoring system has 100 points. 0 is the worst possible score. 100 is the best possible score. Positive changes from baseline indicate an improvement in quality of life and negative changes indicate a deterioration. |
| Part B - Changes From Baseline at 12 Months in Utility Index as Measured by EQ-5D Questionaire | Baseline and 12 months | A measure of how treatment with BAY81-8973 affected the daily life of participants. 1.0 = Best possible score, -0.594 = Worst possible score. Positive changes from baseline indicate an improvement and negative changes indicate a deterioration. |
| Part A - Number of Participants With Inhibitory Antibody Formation | Up to 6 weeks after first injection of study drug | A test to ensure that participants have not developed antibodies that will interfere with the action of BAY81-8973 |
| Part C - Number of Participants With Incidence of Antibody Formation to Heat-shock Protein (HSP-70) | before and 3 weeks after surgery | A test to analyze the formation of antibodies to HSP-70 |
| Part B - Number of Participants With Incidence of Inhibitory Antibody Formation | Up to 12 months after drug administration | A test to ensure that participants have not developed antibodies that will interfere with the action of BAY81-8973 |
| Part C - Number of Participants With Incidence of Inhibitory Antibody Formation | before and 3 weeks after surgery | A test to ensure that participants have not developed antibodies that will interfere with the action of BAY81-8973 |
| Part B - The in Vivo Recovery Values of Human Factor VIII (FVIII) | 15-30 minutes after the injection | The amount of Factor VIII found in blood samples taken after the injection of the study drug at the beginning of the CS/EP treatment period. |
| Part B - Number of Participants With Incidence of Antibody Formation to Heat-shock Protein (HSP-70) | Up to 12 months after drug administration | A test to analyze the formation of antibodies to HSP-70 |
| Part A - Number of Participants With Incidence of Antibody Formation to Host Cell Proteins (HCP) | Up to 4 weeks after drug administration | A test to ensure that participants have not developed antibodies to HCP during the study |
| Part B - Number of Participants With Incidence of Antibody Formation to Host Cell Proteins (HCP) | Up to 12 months after drug administration | A test to ensure that participants have not developed antibodies to HCP during the study |
| Part C - Number of Participants With Incidence of Antibody Formation to Host Cell Proteins (HCP) | before and 3 weeks after surgery | A test to ensure that participants have not developed antibodies to HCP during the study |
| Part B - Number of Participants With Assessment of the Hemostasis During Major Surgery | An average of 1 month after start of treatment | An assessment made by surgeons of how effective BAY81-8973 was in stopping bleeding during major operations |
| Part C - Number of Participants With Assessment of the Hemostasis During Major Surgery | at the time of surgery | An assessment made by surgeons of how effective BAY81-8973 was in stopping bleeding during major operations |
| Part A - Number of Participants With Incidence of Antibody Formation to Heat-shock Protein (HSP-70) | Up to 6 weeks after drug administration | A test to analyze the formation of antibodies to HSP-70 |
| Part B - Annualized Number of Bleeds in Each 6-month Potency Assignment Period | 6 months on each potency | The annualized number of bleeds experienced by participants in each of the two treatment periods |
| Part B - Control of Bleeding as Measured by the Number of Injections Required to Treat a Bleed | 6 months on each potency | The number of injections needed by participants to stop a bleed |
Countries
Argentina, Austria, Croatia, Denmark, Germany, Hong Kong, India, Indonesia, Israel, Italy, Norway, Pakistan, Poland, Serbia, South Africa, Spain, Sweden, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
Participants were recruited from specialized hemophilia treatment centers.
Pre-assignment details
14 participants were enrolled in each of Arms 1 and 2 in Part A. Of these, 11 participants continued into each of Arms 3 and 4 in Part B. Arm 3 enrolled 20 and Arm 4 enrolled 21 additional participants who had not participated in Part A. Arm 5 enrolled 5 participants specifically for surgery in Part C who had not participated in Parts A or B.
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: Recombinant Factor VIII (BAY81-8973) Then Kogenate FS Part A - Arm 1: Participants first received one single intravenous (IV) injection of BAY81-8973 50 IU/kg, then 1 single IV injection of Kogenate FS (BAY14-2222) 50 IU/kg with a wash-out period of at least 2-3 days in between | 14 |
| Arm 2: Kogenate FS Then Recombinant Factor VIII (BAY81-8973) Part A - Arm 2: Participants first received one single intravenous (IV) injection of Kogenate FS (BAY14-2222) 50 IU/kg, then 1 single IV injection of BAY81-8973 50 IU/kg with a wash-out period of at least 2-3 days in between | 14 |
| Arm 3: Recombinant Factor VIII by CS/EP Then by CS/ADJ Part B - Arm 3: Participants received IV injection of BAY81-8973 at 20-50 IU/kg 2-3 times per week with BAY81-8973 measured by Chromogenic Substrate Assay Potency Per European Pharmacopeia for 6 months and then crossed over to study drug measured by Chromogenic Substrate Assay/Adjusted to Label Potency for 6 months | 20 |
| Arm 4: Recombinant Factor VIII by CS/ADJ Then by CS/EP Part B - Arm 4:. Participants received IV injection of BAY81-8973 at 20-50 IU/kg 2-3 times per week with BAY81-8973 measured by Chromogenic Substrate Assay/Adjusted to Label Potency for 6 months and then crossed over to study drug measured by Chromogenic Substrate Assay Per European Pharmacopeia for 6 months | 21 |
| Arm 5: Recombinant Factor VIII (BAY81-8973) by CS/EP - Part C Participants received a loading dose of approximately 50 IU/kg of BAY81-8973 before the first surgical incision, followed by further treatment with BAY81-8973 according to surgical requirements for up to 3 weeks | 5 |
| Total | 74 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Extension Period | Adverse Event | 0 | 0 | 0 | 0 | 0 | 1 |
| Extension Period | non-compliance | 0 | 0 | 0 | 0 | 0 | 1 |
| Extension Period | Physician Decision | 0 | 0 | 0 | 0 | 0 | 1 |
| Extension Period | starting another study | 0 | 0 | 0 | 0 | 0 | 8 |
| Extension Period | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 |
| Part B Treatment Period | Protocol Violation | 0 | 0 | 1 | 0 | 0 | 0 |
| Part B Treatment Period | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Arm 2: Kogenate FS Then Recombinant Factor VIII (BAY81-8973) | Arm 3: Recombinant Factor VIII by CS/EP Then by CS/ADJ | Arm 4: Recombinant Factor VIII by CS/ADJ Then by CS/EP | Arm 1: Recombinant Factor VIII (BAY81-8973) Then Kogenate FS | Arm 5: Recombinant Factor VIII (BAY81-8973) by CS/EP - Part C | Total |
|---|---|---|---|---|---|---|
| Age, Customized Part A < 18 years | 4 Participants | NA Participants | NA Participants | 1 Participants | NA Participants | NA Participants |
| Age, Customized Part A =/> 18 years | 9 Participants | NA Participants | NA Participants | 12 Participants | NA Participants | NA Participants |
| Age, Customized Part B < 18 years | NA Participants | 5 Participants | 5 Participants | NA Participants | NA Participants | NA Participants |
| Age, Customized Part B =/> 18 years | NA Participants | 25 Participants | 27 Participants | NA Participants | NA Participants | NA Participants |
| Age, Customized Part C < 18 years | NA Participants | NA Participants | NA Participants | NA Participants | 0 Participants | NA Participants |
| Age, Customized Part C =/> 18 years | NA Participants | NA Participants | NA Participants | NA Participants | 5 Participants | NA Participants |
| Most recent treatment before enrolment in the study On-demand | 3 Participants | 4 Participants | 8 Participants | 4 Participants | NA Participants | NA Participants |
| Most recent treatment before enrolment in the study Prophylaxis | 11 Participants | 26 Participants | 24 Participants | 10 Participants | NA Participants | NA Participants |
| Sex/Gender, Customized Part A - Female | 0 Participants | NA Participants | NA Participants | 0 Participants | NA Participants | NA Participants |
| Sex/Gender, Customized Part A - Male | 13 Participants | NA Participants | NA Participants | 13 Participants | NA Participants | NA Participants |
| Sex/Gender, Customized Part B - Female | NA Participants | 0 Participants | 0 Participants | NA Participants | NA Participants | NA Participants |
| Sex/Gender, Customized Part B - Male | NA Participants | 30 Participants | 32 Participants | NA Participants | NA Participants | NA Participants |
| Sex/Gender, Customized Part C - Female | NA Participants | NA Participants | NA Participants | NA Participants | 0 Participants | NA Participants |
| Sex/Gender, Customized Part C - Male | NA Participants | NA Participants | NA Participants | NA Participants | 5 Participants | NA Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 27 | 1 / 28 | 43 / 62 | 5 / 7 |
| serious Total, serious adverse events | 0 / 27 | 0 / 28 | 12 / 62 | 1 / 7 |
Outcome results
Primary
Part A - Area Under the Drug Concentration-time Curve (AUC)
To examine the Pharmacokinetic (PK) characteristics of BAY 81-8973 and ensure that the new drug is similar to Kogenate FS. All results are based on the chromogenic assay.
Time frame: Samples taken at pre-injection, and at 0.25, 0.5, 1, 3, 6, 8, 24, 30 and 48 hours post injection. AUC calculated from time of injection to infinity.
Population: PK Analysis Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Recombinant Factor VIII (BAY81-8973) - Part A | Part A - Area Under the Drug Concentration-time Curve (AUC) | 1889.23 Int.units x hours/deciliters (IU*h/dL) | Geometric Coefficient of Variation 36.11 |
| Kogenate FS (BAY14-2222) - Part A | Part A - Area Under the Drug Concentration-time Curve (AUC) | 1583.91 Int.units x hours/deciliters (IU*h/dL) | Geometric Coefficient of Variation 39.89 |
Primary
Part A - Half-life (t 1/2)
To examine the PK characteristics of BAY81-8973 and ensure that the new drug is similar to Kogenate FS. All results are based on the chromogenic assay.
Time frame: Samples taken at pre-injection, and at 0.25, 0.5, 1, 3, 6, 8, 24, 30 and 48 hours post injection.
Population: PK Analysis Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Recombinant Factor VIII (BAY81-8973) - Part A | Part A - Half-life (t 1/2) | 13.77 Hours (h) | Geometric Coefficient of Variation 28 |
| Kogenate FS (BAY14-2222) - Part A | Part A - Half-life (t 1/2) | 12.00 Hours (h) | Geometric Coefficient of Variation 28.2 |
Primary
Part B - Annualized Number of Total Bleeds
The annualized number of bleeds experienced by participants
Time frame: 12 months after randomization
Population: Intent to treat (ITT)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Recombinant Factor VIII (BAY81-8973) - Part A | Part B - Annualized Number of Total Bleeds | 1.03 Bleeds |
Secondary
Part A - Number of Participants With Incidence of Antibody Formation to Heat-shock Protein (HSP-70)
A test to analyze the formation of antibodies to HSP-70
Time frame: Up to 6 weeks after drug administration
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Recombinant Factor VIII (BAY81-8973) - Part A | Part A - Number of Participants With Incidence of Antibody Formation to Heat-shock Protein (HSP-70) | 0 Participants |
Secondary
Part A - Number of Participants With Incidence of Antibody Formation to Host Cell Proteins (HCP)
A test to ensure that participants have not developed antibodies to HCP during the study
Time frame: Up to 4 weeks after drug administration
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Recombinant Factor VIII (BAY81-8973) - Part A | Part A - Number of Participants With Incidence of Antibody Formation to Host Cell Proteins (HCP) | 0 Participants |
Secondary
Part A - Number of Participants With Inhibitory Antibody Formation
A test to ensure that participants have not developed antibodies that will interfere with the action of BAY81-8973
Time frame: Up to 6 weeks after first injection of study drug
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Recombinant Factor VIII (BAY81-8973) - Part A | Part A - Number of Participants With Inhibitory Antibody Formation | 0 Participants |
Secondary
Part B - Annualized Number of Bleeds in Each 6-month Potency Assignment Period
The annualized number of bleeds experienced by participants in each of the two treatment periods
Time frame: 6 months on each potency
Population: ITT. Note: One participant in Part B did not receive any Recombinant Factor VIII measured by the CS/ADJ method, leading to 61 participants (not 62) in that group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Recombinant Factor VIII (BAY81-8973) - Part A | Part B - Annualized Number of Bleeds in Each 6-month Potency Assignment Period | 1.9 Bleeds |
| Kogenate FS (BAY14-2222) - Part A | Part B - Annualized Number of Bleeds in Each 6-month Potency Assignment Period | 1.9 Bleeds |
Secondary
Part B - Changes From Baseline at 12 Months in Quality of Life (QoL) as Measured by Transformed Total Score of Haemo-QoL Questionnaire
A measure of how treatment with BAY81-8973 affected the daily life of participants. the scoring system has 100 points. 0 is the worst possible score. 100 is the best possible score. Positive changes from baseline indicate an improvement in quality of life and negative changes indicate a deterioration.
Time frame: Baseline and 12 months
Population: ITT. Note: Only 51 of the 62 participants had data available for the 12-month QoL analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Recombinant Factor VIII (BAY81-8973) - Part A | Part B - Changes From Baseline at 12 Months in Quality of Life (QoL) as Measured by Transformed Total Score of Haemo-QoL Questionnaire | 2.02 Scores on a scale |
Secondary
Part B - Changes From Baseline at 12 Months in Utility Index as Measured by EQ-5D Questionaire
A measure of how treatment with BAY81-8973 affected the daily life of participants. 1.0 = Best possible score, -0.594 = Worst possible score. Positive changes from baseline indicate an improvement and negative changes indicate a deterioration.
Time frame: Baseline and 12 months
Population: ITT. Note: Only 61 of the 62 participants had data available for the Utility Index of the EQ-5D questionnaire at Month 12.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Recombinant Factor VIII (BAY81-8973) - Part A | Part B - Changes From Baseline at 12 Months in Utility Index as Measured by EQ-5D Questionaire | 0.00 Scores on a scale |
Secondary
Part B - Control of Bleeding as Measured by the Number of Injections Required to Treat a Bleed
The number of injections needed by participants to stop a bleed
Time frame: 6 months on each potency
Population: ITT. Note: One participant in Part B did not receive any Recombinant Factor VIII measured by the CS/ADJ method, leading to 61 participants (not 62) in that group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Recombinant Factor VIII (BAY81-8973) - Part A | Part B - Control of Bleeding as Measured by the Number of Injections Required to Treat a Bleed | 1.0 Injections |
| Kogenate FS (BAY14-2222) - Part A | Part B - Control of Bleeding as Measured by the Number of Injections Required to Treat a Bleed | 1.0 Injections |
Secondary
Part B - Number of Participants With Assessment of the Hemostasis During Major Surgery
An assessment made by surgeons of how effective BAY81-8973 was in stopping bleeding during major operations
Time frame: An average of 1 month after start of treatment
Population: ITT
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Recombinant Factor VIII (BAY81-8973) - Part A | Part B - Number of Participants With Assessment of the Hemostasis During Major Surgery | Excellent | 1 Participants |
| Recombinant Factor VIII (BAY81-8973) - Part A | Part B - Number of Participants With Assessment of the Hemostasis During Major Surgery | Good | 4 Participants |
| Recombinant Factor VIII (BAY81-8973) - Part A | Part B - Number of Participants With Assessment of the Hemostasis During Major Surgery | Moderate | 0 Participants |
| Recombinant Factor VIII (BAY81-8973) - Part A | Part B - Number of Participants With Assessment of the Hemostasis During Major Surgery | Poor | 0 Participants |
Secondary
Part B - Number of Participants With Incidence of Antibody Formation to Heat-shock Protein (HSP-70)
A test to analyze the formation of antibodies to HSP-70
Time frame: Up to 12 months after drug administration
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Recombinant Factor VIII (BAY81-8973) - Part A | Part B - Number of Participants With Incidence of Antibody Formation to Heat-shock Protein (HSP-70) | 1 Participants |
Secondary
Part B - Number of Participants With Incidence of Antibody Formation to Host Cell Proteins (HCP)
A test to ensure that participants have not developed antibodies to HCP during the study
Time frame: Up to 12 months after drug administration
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Recombinant Factor VIII (BAY81-8973) - Part A | Part B - Number of Participants With Incidence of Antibody Formation to Host Cell Proteins (HCP) | 0 Participants |
Secondary
Part B - Number of Participants With Incidence of Inhibitory Antibody Formation
A test to ensure that participants have not developed antibodies that will interfere with the action of BAY81-8973
Time frame: Up to 12 months after drug administration
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Recombinant Factor VIII (BAY81-8973) - Part A | Part B - Number of Participants With Incidence of Inhibitory Antibody Formation | 0 Participants |
Secondary
Part B - The in Vivo Recovery Values of Human Factor VIII (FVIII)
The amount of Factor VIII found in blood samples taken after the injection of the study drug at the beginning of the CS/EP treatment period.
Time frame: 15-30 minutes after the injection
Population: ITT. 1 measurement was taken in all participants at the start of the CS/EP labelled treatment period (CS/ADJ labelled treatment was experimental and will not be used for the future commercial drug, so no measurements were taken). Note: Only 59 of the 62 participants had valid recovery data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Recombinant Factor VIII (BAY81-8973) - Part A | Part B - The in Vivo Recovery Values of Human Factor VIII (FVIII) | 2.50 Kg/dL |
Secondary
Part C - Number of Participants With Assessment of the Hemostasis During Major Surgery
An assessment made by surgeons of how effective BAY81-8973 was in stopping bleeding during major operations
Time frame: at the time of surgery
Population: ITT
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Recombinant Factor VIII (BAY81-8973) - Part A | Part C - Number of Participants With Assessment of the Hemostasis During Major Surgery | Excellent | 1 Participants |
| Recombinant Factor VIII (BAY81-8973) - Part A | Part C - Number of Participants With Assessment of the Hemostasis During Major Surgery | Good | 4 Participants |
| Recombinant Factor VIII (BAY81-8973) - Part A | Part C - Number of Participants With Assessment of the Hemostasis During Major Surgery | Moderate | 0 Participants |
| Recombinant Factor VIII (BAY81-8973) - Part A | Part C - Number of Participants With Assessment of the Hemostasis During Major Surgery | Poor | 0 Participants |
Secondary
Part C - Number of Participants With Incidence of Antibody Formation to Heat-shock Protein (HSP-70)
A test to analyze the formation of antibodies to HSP-70
Time frame: before and 3 weeks after surgery
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Recombinant Factor VIII (BAY81-8973) - Part A | Part C - Number of Participants With Incidence of Antibody Formation to Heat-shock Protein (HSP-70) | 0 Participants |
Secondary
Part C - Number of Participants With Incidence of Antibody Formation to Host Cell Proteins (HCP)
A test to ensure that participants have not developed antibodies to HCP during the study
Time frame: before and 3 weeks after surgery
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Recombinant Factor VIII (BAY81-8973) - Part A | Part C - Number of Participants With Incidence of Antibody Formation to Host Cell Proteins (HCP) | 0 Participants |
Secondary
Part C - Number of Participants With Incidence of Inhibitory Antibody Formation
A test to ensure that participants have not developed antibodies that will interfere with the action of BAY81-8973
Time frame: before and 3 weeks after surgery
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Recombinant Factor VIII (BAY81-8973) - Part A | Part C - Number of Participants With Incidence of Inhibitory Antibody Formation | 0 Participants |