search
Back to results

Trial to Evaluate the Efficacy and Safety of a New Full Length Recombinant Human FVIII for Hemophilia A (Leopold I)

Primary Purpose

Blood Coagulation Disorders, Hemophilia A

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Recombinant Factor VIII (BAY81-8973)
Recombinant Factor VIII (Kogenate FS, BAY14-2222)
Recombinant Factor VIII (BAY81-8973)
Recombinant Factor VIII (BAY81-8973)
Sponsored by
Bayer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Blood Coagulation Disorders focused on measuring Hemophilia A, Factor VIII, Prophylaxis

Eligibility Criteria

12 Years - 65 Years (Child, Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

  • Karolinska Universitetssjukhuset i Solna

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Arm 1: Recombinant Factor VIII (BAY81-8973) then Kogenate FS

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 5: Recombinant Factor VIII by CS/EP

Arm Description

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

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

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

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

Part C - Arm 5: Participants received a loading dose of approximately 50 IU/kg of BAY 81-8973 before the first surgical incision followed by further treatment with BAY 81-8973 according to surgical requirements for up to 3 weeks

Outcomes

Primary Outcome Measures

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.
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.
Part B - Annualized Number of Total Bleeds
The annualized number of bleeds experienced by participants

Secondary Outcome Measures

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.
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
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
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.
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.
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
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
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
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
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
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
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
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
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
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
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

Full Information

First Posted
December 8, 2009
Last Updated
October 14, 2016
Sponsor
Bayer
search

1. Study Identification

Unique Protocol Identification Number
NCT01029340
Brief Title
Trial to Evaluate the Efficacy and Safety of a New Full Length Recombinant Human FVIII for Hemophilia A
Acronym
Leopold I
Official Title
A Two Part Randomized Cross-Over Trial to Evaluate the Pharmacokinetics, Efficacy, and Safety Profile of Plasma Protein-Free Recombinant FVIII Formulated With Sucrose (BAY81-8973) in Previously Treated Subjects With Severe Hemophilia A Under Prophylaxis Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
October 2016
Overall Recruitment Status
Completed
Study Start Date
December 2009 (undefined)
Primary Completion Date
June 2012 (Actual)
Study Completion Date
March 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bayer

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Blood Coagulation Disorders, Hemophilia A
Keywords
Hemophilia A, Factor VIII, Prophylaxis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
74 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1: Recombinant Factor VIII (BAY81-8973) then Kogenate FS
Arm Type
Experimental
Arm Description
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
Arm Title
Arm 2: Kogenate FS then Recombinant Factor VIII (BAY81-8973)
Arm Type
Experimental
Arm Description
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
Arm Title
Arm 3: Recombinant Factor VIII by CS/EP then by CS/ADJ
Arm Type
Experimental
Arm Description
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
Arm Title
Arm 4: Recombinant Factor VIII by CS/ADJ then by CS/EP
Arm Type
Experimental
Arm Description
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
Arm Title
Arm 5: Recombinant Factor VIII by CS/EP
Arm Type
Experimental
Arm Description
Part C - Arm 5: Participants received a loading dose of approximately 50 IU/kg of BAY 81-8973 before the first surgical incision followed by further treatment with BAY 81-8973 according to surgical requirements for up to 3 weeks
Intervention Type
Biological
Intervention Name(s)
Recombinant Factor VIII (BAY81-8973)
Intervention Description
Single dose of BAY81-8973 crossed over to single dose of Kogenate FS
Intervention Type
Biological
Intervention Name(s)
Recombinant Factor VIII (Kogenate FS, BAY14-2222)
Intervention Description
Single dose of Kogenate FS crossed over to Single dose of BAY81-8973
Intervention Type
Biological
Intervention Name(s)
Recombinant Factor VIII (BAY81-8973)
Intervention Description
Participants received IV injections 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 (CS/EP) for 6 months and by Chromogenic Substrate Assay/Adjusted to Label Potency (CS/ADJ) for 6 months, sequence according to randomization.
Intervention Type
Biological
Intervention Name(s)
Recombinant Factor VIII (BAY81-8973)
Intervention Description
Participants received a loading dose of approximately 50 IU/kg of BAY 81-8973 before the first surgical incision followed by further treatment with BAY 81-8973 according to surgical requirements for up to 3 weeks
Primary Outcome Measure Information:
Title
Part A - Area Under the Drug Concentration-time Curve (AUC)
Description
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.
Title
Part A - Half-life (t 1/2)
Description
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.
Title
Part B - Annualized Number of Total Bleeds
Description
The annualized number of bleeds experienced by participants
Time Frame
12 months after randomization
Secondary Outcome Measure Information:
Title
Part B - The in Vivo Recovery Values of Human Factor VIII (FVIII)
Description
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
Title
Part B - Annualized Number of Bleeds in Each 6-month Potency Assignment Period
Description
The annualized number of bleeds experienced by participants in each of the two treatment periods
Time Frame
6 months on each potency
Title
Part B - Control of Bleeding as Measured by the Number of Injections Required to Treat a Bleed
Description
The number of injections needed by participants to stop a bleed
Time Frame
6 months on each potency
Title
Part B - Changes From Baseline at 12 Months in Quality of Life (QoL) as Measured by Transformed Total Score of Haemo-QoL Questionnaire
Description
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
Title
Part B - Changes From Baseline at 12 Months in Utility Index as Measured by EQ-5D Questionaire
Description
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
Title
Part A - Number of Participants With Inhibitory Antibody Formation
Description
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
Title
Part B - Number of Participants With Incidence of Inhibitory Antibody Formation
Description
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
Title
Part C - Number of Participants With Incidence of Inhibitory Antibody Formation
Description
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
Title
Part A - Number of Participants With Incidence of Antibody Formation to Heat-shock Protein (HSP-70)
Description
A test to analyze the formation of antibodies to HSP-70
Time Frame
Up to 6 weeks after drug administration
Title
Part B - Number of Participants With Incidence of Antibody Formation to Heat-shock Protein (HSP-70)
Description
A test to analyze the formation of antibodies to HSP-70
Time Frame
Up to 12 months after drug administration
Title
Part C - Number of Participants With Incidence of Antibody Formation to Heat-shock Protein (HSP-70)
Description
A test to analyze the formation of antibodies to HSP-70
Time Frame
before and 3 weeks after surgery
Title
Part A - Number of Participants With Incidence of Antibody Formation to Host Cell Proteins (HCP)
Description
A test to ensure that participants have not developed antibodies to HCP during the study
Time Frame
Up to 4 weeks after drug administration
Title
Part B - Number of Participants With Incidence of Antibody Formation to Host Cell Proteins (HCP)
Description
A test to ensure that participants have not developed antibodies to HCP during the study
Time Frame
Up to 12 months after drug administration
Title
Part C - Number of Participants With Incidence of Antibody Formation to Host Cell Proteins (HCP)
Description
A test to ensure that participants have not developed antibodies to HCP during the study
Time Frame
before and 3 weeks after surgery
Title
Part B - Number of Participants With Assessment of the Hemostasis During Major Surgery
Description
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
Title
Part C - Number of Participants With Assessment of the Hemostasis During Major Surgery
Description
An assessment made by surgeons of how effective BAY81-8973 was in stopping bleeding during major operations
Time Frame
at the time of surgery

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bayer Study Director
Organizational Affiliation
Bayer
Official's Role
Study Director
Facility Information:
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
City
Tampa
State/Province
Florida
ZIP/Postal Code
33607
Country
United States
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
City
East Lansing
State/Province
Michigan
ZIP/Postal Code
48823
Country
United States
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108-9898
Country
United States
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106-2602
Country
United States
City
Bahia Blanca
State/Province
Buenos Aires
ZIP/Postal Code
B8001HXM
Country
Argentina
City
Rosario
State/Province
Santa Fe
ZIP/Postal Code
S2000CKF
Country
Argentina
City
Graz
ZIP/Postal Code
8036
Country
Austria
City
Wien
ZIP/Postal Code
1090
Country
Austria
City
Zagreb
ZIP/Postal Code
10000
Country
Croatia
City
DK-Aarhus N
ZIP/Postal Code
8200
Country
Denmark
City
Frankfurt
State/Province
Hessen
ZIP/Postal Code
60596
Country
Germany
City
Bonn
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
53127
Country
Germany
City
Mainz
State/Province
Rheinland-Pfalz
ZIP/Postal Code
55131
Country
Germany
City
Homburg
State/Province
Saarland
ZIP/Postal Code
66421
Country
Germany
City
Magdeburg
State/Province
Sachsen-Anhalt
ZIP/Postal Code
39112
Country
Germany
City
Hongkong
Country
Hong Kong
City
Bangalore
ZIP/Postal Code
34
Country
India
City
Mumbai
ZIP/Postal Code
400012
Country
India
City
Pune
ZIP/Postal Code
411005
Country
India
City
Jakarta
ZIP/Postal Code
10430
Country
Indonesia
City
Ramat Gan
ZIP/Postal Code
5262000
Country
Israel
City
Catanzaro
State/Province
Calabria
ZIP/Postal Code
88100
Country
Italy
City
Napoli
State/Province
Campania
ZIP/Postal Code
80131
Country
Italy
City
Napoli
State/Province
Campania
ZIP/Postal Code
80144
Country
Italy
City
Roma
State/Province
Lazio
ZIP/Postal Code
00168
Country
Italy
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20122
Country
Italy
City
Vicenza
State/Province
Veneto
ZIP/Postal Code
36100
Country
Italy
City
Oslo
ZIP/Postal Code
0027
Country
Norway
City
Karachi
ZIP/Postal Code
75300
Country
Pakistan
City
Krakow
ZIP/Postal Code
31-501
Country
Poland
City
Warszawa
ZIP/Postal Code
02-776
Country
Poland
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
City
Beograd
ZIP/Postal Code
11000
Country
Serbia
City
Nis
ZIP/Postal Code
18000
Country
Serbia
City
Novi Sad
ZIP/Postal Code
21000
Country
Serbia
City
Pretoria
State/Province
Gauteng
ZIP/Postal Code
0001
Country
South Africa
City
Parktown
ZIP/Postal Code
2132
Country
South Africa
City
Oviedo
State/Province
Asturias
ZIP/Postal Code
33006
Country
Spain
City
Santander
State/Province
Cantabria
ZIP/Postal Code
39008
Country
Spain
City
A Coruña
ZIP/Postal Code
15006
Country
Spain
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
City
Jaén
ZIP/Postal Code
23007
Country
Spain
City
Valencia
ZIP/Postal Code
46026
Country
Spain
City
Göteborg
ZIP/Postal Code
413 45
Country
Sweden
City
Malmö
ZIP/Postal Code
205 02
Country
Sweden
Facility Name
Karolinska Universitetssjukhuset i Solna
City
Stockholm
ZIP/Postal Code
171 76
Country
Sweden
City
Changhua
ZIP/Postal Code
500
Country
Taiwan
City
Taipei
ZIP/Postal Code
10016
Country
Taiwan
City
Taipei
ZIP/Postal Code
11217
Country
Taiwan
City
Bangkok
ZIP/Postal Code
10330
Country
Thailand
City
Bangkok
ZIP/Postal Code
10400
Country
Thailand
City
Adana
ZIP/Postal Code
01330
Country
Turkey
City
Antalya
ZIP/Postal Code
07059
Country
Turkey
City
Izmir
ZIP/Postal Code
35-100
Country
Turkey
City
Dundee
State/Province
Dundee City
ZIP/Postal Code
DD1 9SY
Country
United Kingdom
City
Oxford
State/Province
Oxfordshire
ZIP/Postal Code
OX3 7LJ
Country
United Kingdom
City
Sheffield
State/Province
South Yorkshire
ZIP/Postal Code
S10 2JF
Country
United Kingdom
City
London
ZIP/Postal Code
SE1 7EH
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
27002680
Citation
Kitchen S, Katterle Y, Beckmann H, Maas Enriquez M. Chromogenic assay for BAY 81-8973 potency assignment has no impact on clinical outcome or monitoring in patient samples. J Thromb Haemost. 2016 Jun;14(6):1192-9. doi: 10.1111/jth.13322. Epub 2016 May 3.
Results Reference
result
PubMed Identifier
26931631
Citation
Oldenburg J, Windyga J, Hampton K, Lalezari S, Tseneklidou-Stoeter D, Beckmann H, Maas Enriquez M. Safety and efficacy of BAY 81-8973 for surgery in previously treated patients with haemophilia A: results of the LEOPOLD clinical trial programme. Haemophilia. 2016 May;22(3):349-53. doi: 10.1111/hae.12839. Epub 2016 Mar 1.
Results Reference
result
PubMed Identifier
27339736
Citation
Saxena K, Lalezari S, Oldenburg J, Tseneklidou-Stoeter D, Beckmann H, Yoon M, Maas Enriquez M. Efficacy and safety of BAY 81-8973, a full-length recombinant factor VIII: results from the LEOPOLD I trial. Haemophilia. 2016 Sep;22(5):706-12. doi: 10.1111/hae.12952. Epub 2016 Jun 24.
Results Reference
derived
Links:
URL
http://www.clinicaltrialsregister.eu/
Description
Click here to find information about studies related to Bayer Healthcare products conducted in Europe

Learn more about this trial

Trial to Evaluate the Efficacy and Safety of a New Full Length Recombinant Human FVIII for Hemophilia A

We'll reach out to this number within 24 hrs