Back to resultsBAX 826 Dose-Escalation Safety Study
Primary Purpose
Hemophilia A
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
BAX 826
Octocog alfa
Sponsored by
About this trial
This is an interventional treatment trial for Hemophilia A
Eligibility Criteria
Inclusion Criteria:
- Previously treated male participants aged 18 to 65 years (inclusive) at the time of screening
- Diagnosis of severe hemophilia A (Factor VIII level <1%)
- Previously treated with FVIII concentrates for ≥150 documented Exposure Days (EDs)
- Karnofsky performance score of ≥60
- Human immunodeficiency virus negative (HIV-); or HIV+ with stable disease
- Hepatitis C virus negative (HCV-); or HCV+ with chronic stable hepatitis as assessed by the investigator
- Able to understand and have provided written informed consent including signature on an informed consent form (ICF) approved by an ethics committee (EC)
- Have provided written authorization for use and disclosure of protected health information
- Agree to abide by the study schedule and to return for the required assessments
- Willing and able to comply with the requirements of the protocol
Exclusion Criteria:
- Detectable FVIII inhibitor at screening, with a titer ≥0.6 Bethesda Unit (BU)
- Documented history of FVIII inhibitors with a titer ≥0.4 BU at any time prior to screening
- Known clinical hypersensitivity towards mouse or hamster proteins or to polysialic acid (PSA)
- Scheduled elective surgery during study participation
- Severe chronic hepatic dysfunction
- Severe renal impairment
- Currently receiving, or has recently received (less than 3 months prior to study participation), or is scheduled to receive during the course of the study, other PSA-ylated drugs
- Have received another investigational drug within 30 days prior to study entry and/or is scheduled to receive additional investigational drug during the course of the study in the context of another investigational drug study
- Diagnosis of an inherited or acquired hemostatic defect other than hemophilia A
- Currently receiving, or scheduled to receive during the course of the study, an immune-modulating drug other than antiretroviral chemotherapy
- Has a clinically significant medical, psychiatric or cognitive illness or recreational drug/alcohol use that, in the opinion of the investigator, would affect the safety or compliance of the participant during the study
- Is a family member or employee of the investigator
Sites / Locations
- UMHAT "Sv. Georgi", EAD
- Werlhof-Institut
- Medizinische Hochschule Hannover
- Vivantes Klinikum im Friedrichshain - Landsberger Allee
- Universitaetsklinikum des Saarlandes
- Universitaetsklinikum Gießen
- Semmelweis Egyetem AOK I.sz. Belgyogyaszati Klinika
- Presidio Ospedaliero di Castelfranco Veneto
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
- Policlinico Umberto I di Roma-Università di Roma La Sapienza
- Radboud University Nijmegen Medical Centre
- Erasmus Medisch Centrum
- Instytut Hematologii i Transfuzjologii
- FSBI "Kirov SR Institute of Hematology and Blood Transfusion FMBA"
- FSBI "Hematological Research Center" MoH of RF
- SBEI HPE "Samara State Medical University" of the MoH of the RF
- Complejo Hospitalario Universitario A Coruña
- Hospital General Universitario de Alicante
- Hospital Universitari Vall d'Hebron
- Hospital Universitario La Paz
- Hospital Regional Universitario de Malaga
- Hospital Universitario Son Espases
- Royal Cornwall Hospital
- Royal London Hospital
- Royal Free Hospital
- St Thomas' Hospital Centre for Haemostasis & Thrombosis
- Manchester Royal Infirmary
- University Hospital of Wales
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Cohort 1 - Low dose
Cohort 2 - Medium dose
Cohort 3 - High dose
Arm Description
The study is comprised of 3 dose cohorts and two dose escalation steps [Cohort 1: 10 evaluable participants; Cohort 2: 10 evaluable participants; Cohort 3: 10 evaluable participants]. Participants will be recruited to the next dose level only after short-term safety has been reviewed and subject to approval by a Safety Review Committee at the preceding dose level.
The study is comprised of 3 dose cohorts and two dose escalation steps [Cohort 1: 10 evaluable participants; Cohort 2: 10 evaluable participants; Cohort 3: 10 evaluable participants]. Participants will be recruited to the next dose level only after short-term safety has been reviewed and subject to approval by a Safety Review Committee at the preceding dose level.
The study is comprised of 3 dose cohorts and two dose escalation steps [Cohort 1: 10 evaluable participants; Cohort 2: 10 evaluable participants; Cohort 3: 10 evaluable participants]. Participants will be recruited to the next dose level only after short-term safety has been reviewed and subject to approval by a Safety Review Committee at the preceding dose level.
Outcomes
Primary Outcome Measures
Serious AEs (SAEs) and Non-serious AEs Occurring After Infusion With BAX 826
Serious Adverse Events and non-serious Adverse Events the occurred after infusion with BAX 826.
Immediate Tolerability (Vital Signs and Clinical Laboratory Assessments)
Clinically significant results after treatment with investigational product that constitute an AE are counted. Vital signs include body temperature, respiratory rate, pulse rate, and blood pressure. Clinical laboratory results include: Hematology (hemoglobin, hematocrit, red blood cell count, white blood cell count with differential (i.e. basophils, eosinophils, lymphocytes, monocytes and neutrophils), international normalized ratio (INR), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), platelet count. Clinical Chemistry: sodium, potassium, chloride, bicarbonate, total protein, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, alkaline phosphatase, gamma-glutamyltransferase (GGT), blood urea nitrogen (BUN), creatinine, glucose. Lipid panel: cholesterol, very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides
Immunogenicity: Inhibitory Antibodies to Factor VIII (FVIII)
Inhibition of FVIII activity by antibodies binding to FVIII were measured using the Nijmegen modification of the Bethesda inhibitor assay.
Immunogenicity: Binding Antibodies to PSA-FVIII (ie BAX 826)
Binding antibodies to PSA FVIII (ie BAX 826) IgG and IgM
Immunogenicity: Binding Antibodies to Factor VIII (FVIII)
Binding antibodies to FVIII IgG and IgM
Immunogenicity: Anti-polysialic Acid (Anti-PSA) Antibodies
Binding antibodies to PSA (IgG and IgM)
Immunogenicity: Anti-Chinese Hamster Ovary (Anti-CHO) Antibodies
Binding antibodies to CHO
Immunogenicity: Human Anti-murine Antibodies (HAMA)
Binding antibodies HAMA (IgG)
Secondary Outcome Measures
Pharmacokinetics: Area Under the Concentration-time Curve From 0 to Infinity (AUC0-∞)
Area under the FVIII activity-time curve from zero extrapolated to infinity, calculated by linear-up/log-down trapezoidal method and extrapolated to infinity, calculated as AUC last + C last / lambda z, where Clast is the estimated concentration at the last quantifiable time point
Pharmacokinetics: Terminal Half-life (t1/2)
Terminal elimination phase half-life, calculated by (ln2)/lambda z, where lambda z is the terminal rate constant, determined by linear regression of the terminal points of the log-linear FVIII activity-time curve.
Pharmacokinetics: Mean Residence Time (MRT)
Mean residence time, calculated as (AUMC 0-∞ / AUC 0-∞) - TI / 2, where TI is the time duration of infusion
Pharmacokinetics: Total Body Clearance (CL)
Systemic body clearance of drug from plasma, calculated by dose (IU/kg)/AUC0-∞
Pharmacokinetics: Incremental Recovery (IR)
Incremental recovery (IR) at Cmax, calculated as IR = (Cmax - Cpreinfusion) / Dose (IU/kg)
Pharmacokinetics: Volume of Distribution at Steady State (Vss)
Volume of distribution at steady state is calculated by MRT*CL MRT=Mean residence time CL=Clearance rate
Pharmacokinetics: Maximum Plasma Concentration (Cmax)
Maximum observed FVIII activity, obtained directly from FVIII activity versus time data
Pharmacokinetics: Time to Maximum Concentration in Plasma (Tmax)
Time of maximum FVIII activity is obtained directly from FVIII activity versus time data
Pharmacokinetics: Area Under the Concentration-time Curve From Time 0 to the Last Quantifiable Time Point (AUC0-last)
Area under the FVIII activity-time curve from zero to the last quantifiable FVIII activity, calculated by linear-up/log-down trapezoidal method.
Pharmacokinetics: Area Under the Concentration-time Curve From 0 to 72 Hours (AUC0-72h)
AUC from time zero to exactly 72 hours, calculated by linear-up/log-down trapezoidal method. If the sample at 72 hours is missing, the activity at 72 hours will be interpolated or extrapolated using the last quantifiable activity and the terminal rate constant (lambda z).
Pharmacokinetics: Area Under the Concentration-time Curve From 0 to 168 Hours (AUC0-168h) for BAX 826
AUC from time zero to exactly 168 hours, calculated by linear-up/log-down trapezoidal method. If the sample at 168 hours is missing, the activity at 168 hours was interpolated or extrapolated using the last quantifiable activity and the terminal rate constant (lambda z). This parameter will be calculated for BAX 826 only.
Comparison of Key Pharmacokinetic Parameters by Cohort
The key pharmacokinetic parameters (Area under the concentration-time curve from 0 to infinity (AUC0-∞), Area under the concentration-time curve from 0 to 72 hours (AUC0-72h), Maximum plasma concentration (Cmax), Terminal half-life (t1/2), Mean residence time (MRT) and Total body clearance (CL)) for ADVATE and BAX 826 have been compared.
Summary of Assessment of Dose Proportionality for BAX 826
Dose Proportionality for BAX 826 was calculated for the parameters Area under the concentration-time curve from 0 to infinity (AUC0-∞), Area under the concentration-time curve from time 0 to the last quantifiable time point (AUC0-last) and Maximum plasma concentration (Cmax).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02716194
Brief Title
BAX 826 Dose-Escalation Safety Study
Official Title
A Phase 1, Prospective, Open Label, Two Period, Fixed Sequence, Dose-Escalation Study of the PK and Safety of BAX 826 (PSA-rFVIII) in Previously Treated Patients With Severe (FVIII <1%) Hemophilia A
Study Type
Interventional
2. Study Status
Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
March 3, 2016 (Actual)
Primary Completion Date
January 17, 2017 (Actual)
Study Completion Date
January 17, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Baxalta now part of Shire
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
To assess tolerability and safety of BAX 826 after a single infusion in previously treated patients (PTPs) with severe hemophilia A
To determine the pharmacokinetic (PK) parameters of BAX 826 compared to ADVATE
To evaluate immunogenicity of polysialic acid linked to Factor VIII (FVIII)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia A
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1 - Low dose
Arm Type
Experimental
Arm Description
The study is comprised of 3 dose cohorts and two dose escalation steps [Cohort 1: 10 evaluable participants; Cohort 2: 10 evaluable participants; Cohort 3: 10 evaluable participants]. Participants will be recruited to the next dose level only after short-term safety has been reviewed and subject to approval by a Safety Review Committee at the preceding dose level.
Arm Title
Cohort 2 - Medium dose
Arm Type
Experimental
Arm Description
The study is comprised of 3 dose cohorts and two dose escalation steps [Cohort 1: 10 evaluable participants; Cohort 2: 10 evaluable participants; Cohort 3: 10 evaluable participants]. Participants will be recruited to the next dose level only after short-term safety has been reviewed and subject to approval by a Safety Review Committee at the preceding dose level.
Arm Title
Cohort 3 - High dose
Arm Type
Experimental
Arm Description
The study is comprised of 3 dose cohorts and two dose escalation steps [Cohort 1: 10 evaluable participants; Cohort 2: 10 evaluable participants; Cohort 3: 10 evaluable participants]. Participants will be recruited to the next dose level only after short-term safety has been reviewed and subject to approval by a Safety Review Committee at the preceding dose level.
Intervention Type
Biological
Intervention Name(s)
BAX 826
Other Intervention Name(s)
BAX826
Intervention Type
Biological
Intervention Name(s)
Octocog alfa
Other Intervention Name(s)
ADVATE (Antihemophilic Factor [Recombinant]), ADVATE
Primary Outcome Measure Information:
Title
Serious AEs (SAEs) and Non-serious AEs Occurring After Infusion With BAX 826
Description
Serious Adverse Events and non-serious Adverse Events the occurred after infusion with BAX 826.
Time Frame
Up to 6 weeks ± 4 days post infusion with BAX826.
Title
Immediate Tolerability (Vital Signs and Clinical Laboratory Assessments)
Description
Clinically significant results after treatment with investigational product that constitute an AE are counted. Vital signs include body temperature, respiratory rate, pulse rate, and blood pressure. Clinical laboratory results include: Hematology (hemoglobin, hematocrit, red blood cell count, white blood cell count with differential (i.e. basophils, eosinophils, lymphocytes, monocytes and neutrophils), international normalized ratio (INR), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), platelet count. Clinical Chemistry: sodium, potassium, chloride, bicarbonate, total protein, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, alkaline phosphatase, gamma-glutamyltransferase (GGT), blood urea nitrogen (BUN), creatinine, glucose. Lipid panel: cholesterol, very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides
Time Frame
Screening (Day -30 to -2); Advate Administration (Study Day 1) pre & postdose, and Day 4; Advate washout 96 hours to 4 weeks; BAX826 Administration Day 1 pre & postdose, Post BAX826 Day 4, 8, 14, and 23; and study termination visit, week 6 ± 4 days
Title
Immunogenicity: Inhibitory Antibodies to Factor VIII (FVIII)
Description
Inhibition of FVIII activity by antibodies binding to FVIII were measured using the Nijmegen modification of the Bethesda inhibitor assay.
Time Frame
Screening visit (Day -30 to -2); Advate Administration (Study Day 1) predose; ADVATE wash out period 96 hours to 4 weeks; BAX826 Administration Day 1 predose, and Post BAX826 Day 8; and study termination visit, week 6 ± 4 days
Title
Immunogenicity: Binding Antibodies to PSA-FVIII (ie BAX 826)
Description
Binding antibodies to PSA FVIII (ie BAX 826) IgG and IgM
Time Frame
Screening visit (Day -30 to -2); Advate Administration (Study Day 1) predose; ADVATE wash out period 96 hours to 4 weeks; BAX826 Administration Day 1 predose, and Post BAX826 Day 8; and study termination visit, week 6 ± 4 days
Title
Immunogenicity: Binding Antibodies to Factor VIII (FVIII)
Description
Binding antibodies to FVIII IgG and IgM
Time Frame
Screening visit (Day -30 to -2); Advate Administration (Study Day 1) predose; ADVATE wash out period 96 hours to 4 weeks; BAX826 Administration Day 1 predose, and Post BAX826 Day 8; and study termination visit, week 6 ± 4 days
Title
Immunogenicity: Anti-polysialic Acid (Anti-PSA) Antibodies
Description
Binding antibodies to PSA (IgG and IgM)
Time Frame
Screening visit (Day -30 to -2); Advate Administration (Study Day 1) predose; ADVATE wash out period 96 hours to 4 weeks; BAX826 Administration Day 1 predose, and Post BAX826 Day 8; and study termination visit, week 6 ± 4 days
Title
Immunogenicity: Anti-Chinese Hamster Ovary (Anti-CHO) Antibodies
Description
Binding antibodies to CHO
Time Frame
Screening visit (Day -30 to -2); Advate Administration (Study Day 1) predose; ADVATE wash out period 96 hours to 4 weeks; BAX826 Administration Day 1 predose, and Post BAX826 Day 8; and study termination visit, week 6 ± 4 days
Title
Immunogenicity: Human Anti-murine Antibodies (HAMA)
Description
Binding antibodies HAMA (IgG)
Time Frame
Screening visit (Day -30 to -2); Advate Administration (Study Day 1) predose; ADVATE wash out period 96 hours to 4 weeks; BAX826 Administration Day 1 predose, and Post BAX826 Day 8; and study termination visit, week 6 ± 4 days
Secondary Outcome Measure Information:
Title
Pharmacokinetics: Area Under the Concentration-time Curve From 0 to Infinity (AUC0-∞)
Description
Area under the FVIII activity-time curve from zero extrapolated to infinity, calculated by linear-up/log-down trapezoidal method and extrapolated to infinity, calculated as AUC last + C last / lambda z, where Clast is the estimated concentration at the last quantifiable time point
Time Frame
Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours.
Title
Pharmacokinetics: Terminal Half-life (t1/2)
Description
Terminal elimination phase half-life, calculated by (ln2)/lambda z, where lambda z is the terminal rate constant, determined by linear regression of the terminal points of the log-linear FVIII activity-time curve.
Time Frame
Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours.
Title
Pharmacokinetics: Mean Residence Time (MRT)
Description
Mean residence time, calculated as (AUMC 0-∞ / AUC 0-∞) - TI / 2, where TI is the time duration of infusion
Time Frame
Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours.
Title
Pharmacokinetics: Total Body Clearance (CL)
Description
Systemic body clearance of drug from plasma, calculated by dose (IU/kg)/AUC0-∞
Time Frame
Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours.
Title
Pharmacokinetics: Incremental Recovery (IR)
Description
Incremental recovery (IR) at Cmax, calculated as IR = (Cmax - Cpreinfusion) / Dose (IU/kg)
Time Frame
Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours.
Title
Pharmacokinetics: Volume of Distribution at Steady State (Vss)
Description
Volume of distribution at steady state is calculated by MRT*CL MRT=Mean residence time CL=Clearance rate
Time Frame
Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours.
Title
Pharmacokinetics: Maximum Plasma Concentration (Cmax)
Description
Maximum observed FVIII activity, obtained directly from FVIII activity versus time data
Time Frame
Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours.
Title
Pharmacokinetics: Time to Maximum Concentration in Plasma (Tmax)
Description
Time of maximum FVIII activity is obtained directly from FVIII activity versus time data
Time Frame
Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours.
Title
Pharmacokinetics: Area Under the Concentration-time Curve From Time 0 to the Last Quantifiable Time Point (AUC0-last)
Description
Area under the FVIII activity-time curve from zero to the last quantifiable FVIII activity, calculated by linear-up/log-down trapezoidal method.
Time Frame
Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours.
Title
Pharmacokinetics: Area Under the Concentration-time Curve From 0 to 72 Hours (AUC0-72h)
Description
AUC from time zero to exactly 72 hours, calculated by linear-up/log-down trapezoidal method. If the sample at 72 hours is missing, the activity at 72 hours will be interpolated or extrapolated using the last quantifiable activity and the terminal rate constant (lambda z).
Time Frame
Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours.
Title
Pharmacokinetics: Area Under the Concentration-time Curve From 0 to 168 Hours (AUC0-168h) for BAX 826
Description
AUC from time zero to exactly 168 hours, calculated by linear-up/log-down trapezoidal method. If the sample at 168 hours is missing, the activity at 168 hours was interpolated or extrapolated using the last quantifiable activity and the terminal rate constant (lambda z). This parameter will be calculated for BAX 826 only.
Time Frame
Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, 72, 96, 120, 144, and 168 hours.
Title
Comparison of Key Pharmacokinetic Parameters by Cohort
Description
The key pharmacokinetic parameters (Area under the concentration-time curve from 0 to infinity (AUC0-∞), Area under the concentration-time curve from 0 to 72 hours (AUC0-72h), Maximum plasma concentration (Cmax), Terminal half-life (t1/2), Mean residence time (MRT) and Total body clearance (CL)) for ADVATE and BAX 826 have been compared.
Time Frame
Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours.
Title
Summary of Assessment of Dose Proportionality for BAX 826
Description
Dose Proportionality for BAX 826 was calculated for the parameters Area under the concentration-time curve from 0 to infinity (AUC0-∞), Area under the concentration-time curve from time 0 to the last quantifiable time point (AUC0-last) and Maximum plasma concentration (Cmax).
Time Frame
Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, 72, 96, 120, 144, and 168 hours.
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Previously treated male participants aged 18 to 65 years (inclusive) at the time of screening
Diagnosis of severe hemophilia A (Factor VIII level <1%)
Previously treated with FVIII concentrates for ≥150 documented Exposure Days (EDs)
Karnofsky performance score of ≥60
Human immunodeficiency virus negative (HIV-); or HIV+ with stable disease
Hepatitis C virus negative (HCV-); or HCV+ with chronic stable hepatitis as assessed by the investigator
Able to understand and have provided written informed consent including signature on an informed consent form (ICF) approved by an ethics committee (EC)
Have provided written authorization for use and disclosure of protected health information
Agree to abide by the study schedule and to return for the required assessments
Willing and able to comply with the requirements of the protocol
Exclusion Criteria:
Detectable FVIII inhibitor at screening, with a titer ≥0.6 Bethesda Unit (BU)
Documented history of FVIII inhibitors with a titer ≥0.4 BU at any time prior to screening
Known clinical hypersensitivity towards mouse or hamster proteins or to polysialic acid (PSA)
Scheduled elective surgery during study participation
Severe chronic hepatic dysfunction
Severe renal impairment
Currently receiving, or has recently received (less than 3 months prior to study participation), or is scheduled to receive during the course of the study, other PSA-ylated drugs
Have received another investigational drug within 30 days prior to study entry and/or is scheduled to receive additional investigational drug during the course of the study in the context of another investigational drug study
Diagnosis of an inherited or acquired hemostatic defect other than hemophilia A
Currently receiving, or scheduled to receive during the course of the study, an immune-modulating drug other than antiretroviral chemotherapy
Has a clinically significant medical, psychiatric or cognitive illness or recreational drug/alcohol use that, in the opinion of the investigator, would affect the safety or compliance of the participant during the study
Is a family member or employee of the investigator
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
UMHAT "Sv. Georgi", EAD
City
Plovdiv
ZIP/Postal Code
4000
Country
Bulgaria
Facility Name
Werlhof-Institut
City
Hannover
State/Province
Niedersachsen
ZIP/Postal Code
30159
Country
Germany
Facility Name
Medizinische Hochschule Hannover
City
Hannover
State/Province
Niedersachsen
ZIP/Postal Code
30625
Country
Germany
Facility Name
Vivantes Klinikum im Friedrichshain - Landsberger Allee
City
Berlin
ZIP/Postal Code
10249
Country
Germany
Facility Name
Universitaetsklinikum des Saarlandes
City
Homburg
ZIP/Postal Code
66421
Country
Germany
Facility Name
Universitaetsklinikum Gießen
City
Marburg
ZIP/Postal Code
35043
Country
Germany
Facility Name
Semmelweis Egyetem AOK I.sz. Belgyogyaszati Klinika
City
Budapest
ZIP/Postal Code
1083
Country
Hungary
Facility Name
Presidio Ospedaliero di Castelfranco Veneto
City
Castelfranco Veneto
State/Province
Treviso
ZIP/Postal Code
31033
Country
Italy
Facility Name
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
City
Milano
ZIP/Postal Code
20122
Country
Italy
Facility Name
Policlinico Umberto I di Roma-Università di Roma La Sapienza
City
Roma
ZIP/Postal Code
00144
Country
Italy
Facility Name
Radboud University Nijmegen Medical Centre
City
Nijmegen
ZIP/Postal Code
6525 GA
Country
Netherlands
Facility Name
Erasmus Medisch Centrum
City
Rotterdam
ZIP/Postal Code
3015 AA
Country
Netherlands
Facility Name
Instytut Hematologii i Transfuzjologii
City
Warszawa
ZIP/Postal Code
02-776
Country
Poland
Facility Name
FSBI "Kirov SR Institute of Hematology and Blood Transfusion FMBA"
City
Kirov
ZIP/Postal Code
610027
Country
Russian Federation
Facility Name
FSBI "Hematological Research Center" MoH of RF
City
Moscow
ZIP/Postal Code
125167
Country
Russian Federation
Facility Name
SBEI HPE "Samara State Medical University" of the MoH of the RF
City
Samara
ZIP/Postal Code
443099
Country
Russian Federation
Facility Name
Complejo Hospitalario Universitario A Coruña
City
A Coruña
State/Province
La Coruña
ZIP/Postal Code
15006
Country
Spain
Facility Name
Hospital General Universitario de Alicante
City
Alicante
ZIP/Postal Code
03010
Country
Spain
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Universitario La Paz
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Hospital Regional Universitario de Malaga
City
Malaga
ZIP/Postal Code
29010
Country
Spain
Facility Name
Hospital Universitario Son Espases
City
Palma de Mallorca
ZIP/Postal Code
07120
Country
Spain
Facility Name
Royal Cornwall Hospital
City
Truro
State/Province
Cornwall
ZIP/Postal Code
TR1 3LJ
Country
United Kingdom
Facility Name
Royal London Hospital
City
London
State/Province
Greater London
ZIP/Postal Code
E1 1BB
Country
United Kingdom
Facility Name
Royal Free Hospital
City
London
State/Province
Greater London
ZIP/Postal Code
NW3 2QG
Country
United Kingdom
Facility Name
St Thomas' Hospital Centre for Haemostasis & Thrombosis
City
London
State/Province
Greater London
ZIP/Postal Code
SE1 7EH
Country
United Kingdom
Facility Name
Manchester Royal Infirmary
City
Manchester
State/Province
Greater Manchester
ZIP/Postal Code
M13 9WL
Country
United Kingdom
Facility Name
University Hospital of Wales
City
Cardiff
State/Province
West Glamorgan
ZIP/Postal Code
CF14 4XW
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
31778283
Citation
Tiede A, Allen G, Bauer A, Chowdary P, Collins P, Goldstein B, Jiang HJ, Kӧck K, Takacs I, Timofeeva M, Wolfsegger M, Srivastava S. SHP656, a polysialylated recombinant factor VIII (PSA-rFVIII): First-in-human study evaluating safety, tolerability and pharmacokinetics in patients with severe haemophilia A. Haemophilia. 2020 Jan;26(1):47-55. doi: 10.1111/hae.13878. Epub 2019 Nov 28.
Results Reference
derived
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BAX 826 Dose-Escalation Safety Study
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