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Study Investigating a PEGylated Recombinant Factor VIII (BAX 855) for Hemophilia A (PROLONG-ATE Study)

Primary Purpose

Hemophilia A

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method
PEGylated Recombinant Factor VIII
PEGylated Recombinant Factor VIII
PEGylated Recombinant Factor VIII
Sponsored by
Baxalta now part of Shire
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Hemophilia A

Eligibility Criteria

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

Main Inclusion Criteria:

  • Participant and/or legal representative has/have voluntarily provided signed informed consent
  • Participant is 12 to 65 years old at the time of screening
  • Participant is male with severe hemophilia A (Factor VIII (FVIII) clotting activity < 1%) as confirmed by central laboratory at screening after the appropriate washout period or a documented FVIII clotting activity <1%
  • Participant has been previously treated with plasma-derived FVIII concentrates or recombinant FVIII for ≥150 documented exposure days (EDs)
  • Participant is currently receiving prophylaxis or on-demand therapy with FVIII
  • Participant is willing and able to comply with the requirements of the protocol

Main Exclusion Criteria:

  • Participant has detectable FVIII inhibitory antibodies (≥ 0.6 Bethesda Units (BU) using the Nijmegen modification of the Bethesda assay) as confirmed by central laboratory at screening
  • Participant has history of FVIII inhibitory antibodies (≥ 0.4 BU using the Nijmegen modification of the Bethesda assay or ≥ 0.6 BU using the Bethesda assay) at any time prior to screening
  • Participant has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia A (eg, qualitative platelet defect or von Willebrand's disease).

Sites / Locations

  • University of Colorado
  • University of Florida, College of Medicine
  • Children's Healthcare of Atlanta
  • Bleeding and Clotting Disorders Institute
  • University of Kentucky Medical Center
  • University of Louisville Hospital
  • Tulane University Medical School
  • Children's Mercy Hospitals & Clinics
  • Weill Cornell Medical College-New York Presbyterian Hospital
  • University of North Carolina Chapel Hill
  • Duke University Medical Center
  • Cincinnati Children's Hospital Medical Center
  • The Cleveland Clinic Foundation
  • Penn State Milton S. Hershey Medical Center
  • Palmetto Health
  • University of Utah Health Sciences Center
  • Puget Sound Blood Group
  • Royal Adelaide Hospital
  • The Alfred Hospital
  • Fremantle Hospital
  • Hollywood Specialist Centre
  • Landes-Frauen-und Kinderklinik Linz
  • AKH - Medizinische Universität Wien
  • SHAT of Oncohaematology Diseases
  • Fakultni nemocnice Brno
  • Fakultni nemocnice Olomouc
  • Fakultni nemocnice v Motole
  • Gerinnungszentrum Rhein-Ruhr
  • Vivantes Klinikum im Friedrichshain - Landsberger Allee
  • Universitaetsklinikum Hamburg-Eppendorf
  • Werlhof-Institut MVZ
  • Rambam Health Care Campus
  • Chaim Sheba Medical Center
  • Nagoya University Hospital
  • University of Occupational and Environmental Health Hospital
  • Hiroshima University Hospital
  • Hyogo College of Medicine Hospital
  • St. Marianna University School of Medicine Hospital
  • Nara Medical University Hospital
  • Tokyo Medical University Hospital
  • Ogikubo Hospital
  • Chonnam National University Hwasun Hospital
  • Pusan National University Hospital
  • Eulji University Hospital
  • Kyung hee University Hospital at Gangdong
  • Ulsan University Hospital
  • Vilnius University Hospital Santariskiu Clinics, Public Institution
  • Children's Hospital, Affiliate of Vilnius University Hospital Santariskiu Klinikos
  • Hospital Pulau Pinang
  • Hospital Tengku Ampuan Rahimah
  • Pusat Darah Negara
  • Academisch Medisch Centrum
  • Uniwersyteckie Centrum Kliniczne
  • Wojewodzki Szpital Specjalistyczny im.M.Kopernika w Lodzi
  • Sanador SRL
  • Hospital Universitari Son Espases
  • Complejo Hospitalario Universitario A Coruña
  • Hospital Regional Universitario de Malaga
  • Hospital Universitari i Politecnic La Fe
  • Skånes Universitetssjukhus, Malmö
  • Karolinska Universitetssjukhuset, Solna
  • Universitatsspital Zurich
  • Tri-Service General Hospital
  • SI V.K.Gusak Emergency and Reconstructive Surgery Institute of NAMSU Center of IT
  • SI Institute of Blood Pathology and Transfusion Medicine of NAMSU
  • Bristol Royal Hospital for Children
  • Royal Free Hospital
  • St Thomas' Hospital
  • Manchester Royal Infirmary
  • Royal Manchester Children's Hospital
  • Leicester Royal Infirmary
  • Churchill Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Prophylaxis

On-demand

Arm Description

Outcomes

Primary Outcome Measures

Annualized Bleeding Rate (ABR)
Comparisons between prophylactic and on-demand treatment were based on ABR estimates from a negative binomial regression model, taking into account the treatment regimen, target joints and age at screening, and duration of the observation period for efficacy.

Secondary Outcome Measures

Rate of Success of BAX 855 for Treatment of Bleeding Episodes
Success in the control of bleeding was defined as a rating of excellent or good using the Efficacy Rating Scale for Treatment of Bleeding Episodes measured 24 hours after initiation of treatment for the bleeding episode. EXCELLENT: Full relief of pain and cessation of objective signs of bleeding (eg, swelling, tenderness, and decreased range of motion in the case of musculoskeletal hemorrhage) after a single infusion. No additional infusion is required for the control of bleeding. Administration of further infusions to maintain hemostasis would not affect this scoring. GOOD: Definite pain relief and/or improvement in signs of bleeding after a single infusion. Possibly requires more than 1 infusion for complete resolution. FAIR: Probable and/or slight relief of pain and slight improvement in signs of bleeding after a single infusion. Required more than 1 infusion for complete resolution. NONE: No improvement or condition worsens.
Average Number of BAX 855 Infusions Needed for the Treatment of Bleeding Episodes
Number of Participants With ≤1, 2, 3, 4, 5, 6, or >6 Month Time Intervals Between Bleeding Episodes or no Bleeding Episodes
Interval between Bleeds in months was calculated as: Observation period for efficacy (in days)/(number of bleeds)*(12/365.2425)
Weight-adjusted Consumption of BAX 855 - Per Prophylactic Infusion and Pharmacokinetic (PK) Infusion
Weight-adjusted Consumption of BAX 855 - Per Treatment of Bleeding Episode (BE) and Per BE for Maintenance of Hemostasis
Infusions per bleeding episode for maintenance of hemostasis only includes infusions following the resolution of a bleed to maintain hemostasis.
Percentage of Participants With Adverse Events
Adverse Events (AEs) and Serious Adverse Events (SAEs)
Immunogenicity - Number of Participants With Positive Inhibitory Antibodies to FVIII, Binding Antibodies to FVIII, PEG-VIII, PEG and Anti-CHO Antibodies at Study Completion/Termination
Number of participants who received BAX855, with immunogenicity data from study completion/termination visit. FVIII = factor VIII; PEG-VIII = polyethylene glycol-factor VIII; Anti-CHO = Anti-Chinese hamster ovary
Patient Reported Outcomes: Haemo-SYM Questionnaire, Change in Score From Baseline to End of Study
The HAEMO-SYM has two subscales: pain and bleeds. HAEMO-SYM subscale scores are calculated by taking the mean of the items in each subscale and transforming them to a 0 (none or absent) to 100 (very severe) scale. Given that higher scores indicate more severe symptoms on the Haemo-SYM and that the change scores were calculated as the value at study completion minus the value at baseline, a negative change score indicates an improvement (reduction in symptoms). Conversely, a positive change score indicates worsening symptoms.
Patient Reported Outcomes - Short Form (SF)-36, Change From Baseline to End of Study
Change from Baseline to End of Study for SF-36 Questionnaire is provided. Scores for individual SF-36 categories range from 0 to 100 with higher scores representing better health. Given that higher scores indicate better health-related quality of life (HRQoL) and that the change scores were calculated as the value at study completion minus the value at baseline, a negative change score indicates a worsening of HRQoL.
Pharmacokinetics (Pk) - Plasma Half-life (One-stage Clotting Assay)
Terminal half-life calculated as log_e2/λz where λz is the terminal elimination rate constant. Participants in the pharmacokinetic full analysis set (PKFAS) analysis set received an initial infusion of ADVATE for pharmacokinetic analysis (PK-1) followed by a washout period and an infusion of BAX 855 for a second pharmacokinetic analysis (PK-2). After at least 50 EDs of BAX 855, participants in the PK subgroup received another infusion of BAX 855 for pharmacokinetic analysis (PK-3).
Pharmacokinetics (Pk) - Mean Residence Time (One-stage Clotting Assay)
The mean residence time (MRT) w as calculated as total area under the moment curve divided by the total area under the curve starting from the begin of infusion (or the end of infusion if start time is not available). Participants in the pharmacokinetic full analysis set (PKFAS) analysis set received an initial infusion of ADVATE for pharmacokinetic analysis (PK-1) followed by a washout period and an infusion of BAX 855 for a second pharmacokinetic analysis (PK-2). After at least 50 EDs of BAX 855, participants in the PK subgroup received another infusion of BAX 855 for pharmacokinetic analysis (PK-3).
Pharmacokinetics (Pk) - Total Body Clearance (One-stage Clotting Assay)
Clearance in dL/(kg.h) will be calculated as the dose in IU/kg divided by the total area under the curve starting from the begin of infusion (or the end of infusion if start time is not available). Participants in the pharmacokinetic full analysis set (PKFAS) analysis set received an initial infusion of ADVATE for pharmacokinetic analysis (PK-1) followed by a washout period and an infusion of BAX 855 for a second pharmacokinetic analysis (PK-2). After at least 50 EDs of BAX 855, participants in the PK subgroup received another infusion of BAX 855 for pharmacokinetic analysis (PK-3).
Pharmacokinetics (Pk) - Incremental Recovery Over Time (One-stage Clotting Assay)
Incremental recovery (IR) in (IU/dL)/ (IU/kg) calculated as: IR = (Cmax- (C pre-infusion)) / (Dose/kg), where C =concentration. Participants in the pharmacokinetic full analysis set (PKFAS) analysis set received an initial infusion of ADVATE for pharmacokinetic analysis (PK-1) followed by a washout period and an infusion of BAX 855 for a second pharmacokinetic analysis (PK-2). After at least 50 EDs of BAX 855, participants in the PK subgroup received another infusion of BAX 855 for pharmacokinetic analysis (PK-3).
Pharmacokinetics (Pk) - Area Under the Concentration Versus Time Curve From 0 to Infinity (AUC0-∞) (One-stage Clotting Assay)
Calculated by WinNonlin NCA (Model 201, calculation method: Linear Trapezoidal Linear/Log Interpolation). Participants in the pharmacokinetic full analysis set (PKFAS) analysis set received an initial infusion of ADVATE for pharmacokinetic analysis (PK-1) followed by a washout period and an infusion of BAX 855 for a second pharmacokinetic analysis (PK-2). After at least 50 EDs of BAX 855, participants in the PK subgroup received another infusion of BAX 855 for pharmacokinetic analysis (PK-3).
Pharmacokinetics (Pk) - Apparent Volume of Distribution at Steady State (Vss) (One-stage Clotting Assay)
The apparent volume of distribution at steady state (Vss) will be calculated as: Vss = Clearance * Mean Residence Time. Participants in the pharmacokinetic full analysis set (PKFAS) analysis set received an initial infusion of ADVATE for pharmacokinetic analysis (PK-1) followed by a washout period and an infusion of BAX 855 for a second pharmacokinetic analysis (PK-2). After at least 50 EDs of BAX 855, participants in the PK subgroup received another infusion of BAX 855 for pharmacokinetic analysis (PK-3).
Pharmacokinetics (Pk) - Maximum Plasma Concentration (Cmax) (One-stage Clotting Assay)
Participants in the pharmacokinetic full analysis set (PKFAS) analysis set received an initial infusion of ADVATE for pharmacokinetic analysis (PK-1) followed by a washout period and an infusion of BAX 855 for a second pharmacokinetic analysis (PK-2). After at least 50 EDs of BAX 855, participants in the PK subgroup received another infusion of BAX 855 for pharmacokinetic analysis (PK-3).
Pharmacokinetics (Pk) -Time to Maximum Concentration in Plasma (Tmax) (One-stage Clotting Assay)
Tmax in hours will be defined as the time to reach Cmax. Participants in the pharmacokinetic full analysis set (PKFAS) analysis set received an initial infusion of ADVATE for pharmacokinetic analysis (PK-1) followed by a washout period and an infusion of BAX 855 for a second pharmacokinetic analysis (PK-2). After at least 50 EDs of BAX 855, participants in the PK subgroup received another infusion of BAX 855 for pharmacokinetic analysis (PK-3).
Change in Vital Signs From Screening - Temperature
Change in Vital Signs From Screening - Pulse Rate
Change in Vital Signs From Screening - Respiratory Rate
Changes in Vital Signs From Screening - Blood Pressure
Systolic Blood Pressure (SBP) Diastolic Blood Pressure (DBP)
Changes in Clinical Chemistry Laboratory Assessments From Screening - Albumin and Protein
Changes in Clinical Chemistry Laboratory Assessments From Screening - Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase
Alkaline Phosphatase (Alk Phos); Alanine Aminotransferase (Ala Amino); Aspartate Aminotransferase (Asp Amino)
Changes in Clinical Chemistry Laboratory Assessments From Screening - Bicarbonate, Chloride, Glucose, Potassium, Sodium, Blood Urea Nitrogen (BUN)
Changes in Clinical Chemistry Laboratory Assessments From Screening - Creatinine, and Bilirubin
Changes in Hematology Laboratory Assessments From Screening - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, and Leukocytes
Changes in Hematology Laboratory Assessments From Screening - Hematocrit
Changes in Hematology Laboratory Assessments From Screening - Hemoglobin
Changes in Hematology Laboratory Assessments From Screening - Erythrocytes
Changes in Lipid Panel Assessments From Screening - Cholesterol; High Density Lipoprotein (HDL); Low Density Lipoprotein (LDL); Triglycerides; and Very Low Density Lipoprotein (VLDL)

Full Information

First Posted
November 21, 2012
Last Updated
April 30, 2021
Sponsor
Baxalta now part of Shire
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1. Study Identification

Unique Protocol Identification Number
NCT01736475
Brief Title
Study Investigating a PEGylated Recombinant Factor VIII (BAX 855) for Hemophilia A (PROLONG-ATE Study)
Official Title
A Phase 2/3, Multi-Center, Open Label Study of Efficacy, Safety, and Pharmacokinetics of PEGylated Recombinant Factor VIII (BAX 855) Administered for Prophylaxis and Treatment of Bleeding in Previously Treated Patients With Severe Hemophilia A
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
January 31, 2013 (Actual)
Primary Completion Date
July 17, 2014 (Actual)
Study Completion Date
July 17, 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Baxalta now part of Shire

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
To assess efficacy and safety, including immunogenicity of BAX 855 administered as prophylaxis and as on-demand therapy in adult and adolescent (12-65 years) previously treated patients (PTPs) with severe hemophilia A To determine the pharmacokinetic (PK) parameters of BAX 855.

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
Prevention
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
159 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Prophylaxis
Arm Type
Experimental
Arm Title
On-demand
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method
Other Intervention Name(s)
ADVATE
Intervention Description
Pharmacokinetic (PK) evaluation of ADVATE
Intervention Type
Biological
Intervention Name(s)
PEGylated Recombinant Factor VIII
Other Intervention Name(s)
BAX 855
Intervention Description
Pharmacokinetic (PK) evaluation of BAX 855
Intervention Type
Biological
Intervention Name(s)
PEGylated Recombinant Factor VIII
Other Intervention Name(s)
BAX 855
Intervention Description
Prophylaxis treatment
Intervention Type
Biological
Intervention Name(s)
PEGylated Recombinant Factor VIII
Other Intervention Name(s)
BAX 855
Intervention Description
On-demand treatment
Primary Outcome Measure Information:
Title
Annualized Bleeding Rate (ABR)
Description
Comparisons between prophylactic and on-demand treatment were based on ABR estimates from a negative binomial regression model, taking into account the treatment regimen, target joints and age at screening, and duration of the observation period for efficacy.
Time Frame
9 months
Secondary Outcome Measure Information:
Title
Rate of Success of BAX 855 for Treatment of Bleeding Episodes
Description
Success in the control of bleeding was defined as a rating of excellent or good using the Efficacy Rating Scale for Treatment of Bleeding Episodes measured 24 hours after initiation of treatment for the bleeding episode. EXCELLENT: Full relief of pain and cessation of objective signs of bleeding (eg, swelling, tenderness, and decreased range of motion in the case of musculoskeletal hemorrhage) after a single infusion. No additional infusion is required for the control of bleeding. Administration of further infusions to maintain hemostasis would not affect this scoring. GOOD: Definite pain relief and/or improvement in signs of bleeding after a single infusion. Possibly requires more than 1 infusion for complete resolution. FAIR: Probable and/or slight relief of pain and slight improvement in signs of bleeding after a single infusion. Required more than 1 infusion for complete resolution. NONE: No improvement or condition worsens.
Time Frame
At least 50 exposure days or 6 months (±2 weeks), whichever occurs last, for the prophylaxis arm and 6 months (± 2 weeks) for the on-demand arm.
Title
Average Number of BAX 855 Infusions Needed for the Treatment of Bleeding Episodes
Time Frame
From first exposure to BAX 855 until the end of the study, [at least 50 exposure days or 6 months (±2 weeks), whichever occurs last, for the prophylaxis arm; and 6 months (± 2 weeks) for the on-demand arm].
Title
Number of Participants With ≤1, 2, 3, 4, 5, 6, or >6 Month Time Intervals Between Bleeding Episodes or no Bleeding Episodes
Description
Interval between Bleeds in months was calculated as: Observation period for efficacy (in days)/(number of bleeds)*(12/365.2425)
Time Frame
From first exposure to BAX 855 until the end of the study, [at least 50 exposure days or 6 months (±2 weeks), whichever occurs last, for the prophylaxis arm; and 6 months (± 2 weeks) for the on-demand arm].
Title
Weight-adjusted Consumption of BAX 855 - Per Prophylactic Infusion and Pharmacokinetic (PK) Infusion
Time Frame
Prophylactic Infusion: ≥50 exposure days or 6 months (±2 weeks), whichever occurs last. PK Infusion: PK #1 Pre-infusion within 30 minutes; Post-infusion 10 min, and 0.5, 1, 3, 6, 24, 32, 48, 56 hours (h). PK #2 also at Post-infusion 96h
Title
Weight-adjusted Consumption of BAX 855 - Per Treatment of Bleeding Episode (BE) and Per BE for Maintenance of Hemostasis
Description
Infusions per bleeding episode for maintenance of hemostasis only includes infusions following the resolution of a bleed to maintain hemostasis.
Time Frame
Treatment of Bleeding Episode (BE): Minor/Moderate BE every 12 to 24 hours until bleeding is resolved; Major BE every 8 to 12 hours until bleeding is resolved. Per BE for Maintenance of Hemostasis: within 48 hours after bleeding episode resolution.
Title
Percentage of Participants With Adverse Events
Description
Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame
From first exposure to BAX 855 until the end of the study, [at least 50 exposure days or 6 months (±2 weeks), whichever occurs last, for the prophylaxis arm; and 6 months (± 2 weeks) for the on-demand arm].
Title
Immunogenicity - Number of Participants With Positive Inhibitory Antibodies to FVIII, Binding Antibodies to FVIII, PEG-VIII, PEG and Anti-CHO Antibodies at Study Completion/Termination
Description
Number of participants who received BAX855, with immunogenicity data from study completion/termination visit. FVIII = factor VIII; PEG-VIII = polyethylene glycol-factor VIII; Anti-CHO = Anti-Chinese hamster ovary
Time Frame
From first exposure to BAX 855 until the end of the study, [at least 50 exposure days or 6 months (±2 weeks), whichever occurs last, for the prophylaxis arm; and 6 months (± 2 weeks) for the on-demand arm].
Title
Patient Reported Outcomes: Haemo-SYM Questionnaire, Change in Score From Baseline to End of Study
Description
The HAEMO-SYM has two subscales: pain and bleeds. HAEMO-SYM subscale scores are calculated by taking the mean of the items in each subscale and transforming them to a 0 (none or absent) to 100 (very severe) scale. Given that higher scores indicate more severe symptoms on the Haemo-SYM and that the change scores were calculated as the value at study completion minus the value at baseline, a negative change score indicates an improvement (reduction in symptoms). Conversely, a positive change score indicates worsening symptoms.
Time Frame
Baseline; and end of study visit [at least 50 exposure days or 6 months (±2 weeks), whichever occurs last, for the prophylaxis arm and 6 months (± 2 weeks) for the on-demand arm].
Title
Patient Reported Outcomes - Short Form (SF)-36, Change From Baseline to End of Study
Description
Change from Baseline to End of Study for SF-36 Questionnaire is provided. Scores for individual SF-36 categories range from 0 to 100 with higher scores representing better health. Given that higher scores indicate better health-related quality of life (HRQoL) and that the change scores were calculated as the value at study completion minus the value at baseline, a negative change score indicates a worsening of HRQoL.
Time Frame
Baseline; and end of study visit [at least 50 exposure days or 6 months (±2 weeks), whichever occurs last, for the prophylaxis arm and 6 months (± 2 weeks) for the on-demand arm]
Title
Pharmacokinetics (Pk) - Plasma Half-life (One-stage Clotting Assay)
Description
Terminal half-life calculated as log_e2/λz where λz is the terminal elimination rate constant. Participants in the pharmacokinetic full analysis set (PKFAS) analysis set received an initial infusion of ADVATE for pharmacokinetic analysis (PK-1) followed by a washout period and an infusion of BAX 855 for a second pharmacokinetic analysis (PK-2). After at least 50 EDs of BAX 855, participants in the PK subgroup received another infusion of BAX 855 for pharmacokinetic analysis (PK-3).
Time Frame
Within 30 minutes prior to start of infusion; and post-infusion at 10, 30 minutes, and 1, 3, 6, 9, 24, 32, 48, 56, 72 (PK2 and PK3 only), and 96 hours (PK2 and PK3 only).
Title
Pharmacokinetics (Pk) - Mean Residence Time (One-stage Clotting Assay)
Description
The mean residence time (MRT) w as calculated as total area under the moment curve divided by the total area under the curve starting from the begin of infusion (or the end of infusion if start time is not available). Participants in the pharmacokinetic full analysis set (PKFAS) analysis set received an initial infusion of ADVATE for pharmacokinetic analysis (PK-1) followed by a washout period and an infusion of BAX 855 for a second pharmacokinetic analysis (PK-2). After at least 50 EDs of BAX 855, participants in the PK subgroup received another infusion of BAX 855 for pharmacokinetic analysis (PK-3).
Time Frame
Within 30 minutes prior to start of infusion; and post-infusion at 10, 30 minutes, and 1, 3, 6, 9, 24, 32, 48, 56, 72 (PK2 and PK3 only), and 96 hours (PK2 and PK3 only).
Title
Pharmacokinetics (Pk) - Total Body Clearance (One-stage Clotting Assay)
Description
Clearance in dL/(kg.h) will be calculated as the dose in IU/kg divided by the total area under the curve starting from the begin of infusion (or the end of infusion if start time is not available). Participants in the pharmacokinetic full analysis set (PKFAS) analysis set received an initial infusion of ADVATE for pharmacokinetic analysis (PK-1) followed by a washout period and an infusion of BAX 855 for a second pharmacokinetic analysis (PK-2). After at least 50 EDs of BAX 855, participants in the PK subgroup received another infusion of BAX 855 for pharmacokinetic analysis (PK-3).
Time Frame
Within 30 minutes prior to start of infusion; and post-infusion at 10, 30 minutes, and 1, 3, 6, 9, 24, 32, 48, 56, 72 (PK2 and PK3 only), and 96 hours (PK2 and PK3 only).
Title
Pharmacokinetics (Pk) - Incremental Recovery Over Time (One-stage Clotting Assay)
Description
Incremental recovery (IR) in (IU/dL)/ (IU/kg) calculated as: IR = (Cmax- (C pre-infusion)) / (Dose/kg), where C =concentration. Participants in the pharmacokinetic full analysis set (PKFAS) analysis set received an initial infusion of ADVATE for pharmacokinetic analysis (PK-1) followed by a washout period and an infusion of BAX 855 for a second pharmacokinetic analysis (PK-2). After at least 50 EDs of BAX 855, participants in the PK subgroup received another infusion of BAX 855 for pharmacokinetic analysis (PK-3).
Time Frame
Within 30 minutes prior to start of infusion; and post-infusion at 10, 30 minutes, and 1, 3, 6, 9, 24, 32, 48, 56, 72 (PK2 and PK3 only), and 96 hours (PK2 and PK3 only).
Title
Pharmacokinetics (Pk) - Area Under the Concentration Versus Time Curve From 0 to Infinity (AUC0-∞) (One-stage Clotting Assay)
Description
Calculated by WinNonlin NCA (Model 201, calculation method: Linear Trapezoidal Linear/Log Interpolation). Participants in the pharmacokinetic full analysis set (PKFAS) analysis set received an initial infusion of ADVATE for pharmacokinetic analysis (PK-1) followed by a washout period and an infusion of BAX 855 for a second pharmacokinetic analysis (PK-2). After at least 50 EDs of BAX 855, participants in the PK subgroup received another infusion of BAX 855 for pharmacokinetic analysis (PK-3).
Time Frame
Within 30 minutes prior to start of infusion; and post-infusion at 10, 30 minutes, and 1, 3, 6, 9, 24, 32, 48, 56, 72 (PK2 and PK3 only), and 96 hours (PK2 and PK3 only).
Title
Pharmacokinetics (Pk) - Apparent Volume of Distribution at Steady State (Vss) (One-stage Clotting Assay)
Description
The apparent volume of distribution at steady state (Vss) will be calculated as: Vss = Clearance * Mean Residence Time. Participants in the pharmacokinetic full analysis set (PKFAS) analysis set received an initial infusion of ADVATE for pharmacokinetic analysis (PK-1) followed by a washout period and an infusion of BAX 855 for a second pharmacokinetic analysis (PK-2). After at least 50 EDs of BAX 855, participants in the PK subgroup received another infusion of BAX 855 for pharmacokinetic analysis (PK-3).
Time Frame
Within 30 minutes prior to start of infusion; and post-infusion at 10, 30 minutes, and 1, 3, 6, 9, 24, 32, 48, 56, 72 (PK2 and PK3 only), and 96 hours (PK2 and PK3 only).
Title
Pharmacokinetics (Pk) - Maximum Plasma Concentration (Cmax) (One-stage Clotting Assay)
Description
Participants in the pharmacokinetic full analysis set (PKFAS) analysis set received an initial infusion of ADVATE for pharmacokinetic analysis (PK-1) followed by a washout period and an infusion of BAX 855 for a second pharmacokinetic analysis (PK-2). After at least 50 EDs of BAX 855, participants in the PK subgroup received another infusion of BAX 855 for pharmacokinetic analysis (PK-3).
Time Frame
Within 30 minutes prior to start of infusion; and post-infusion at 10, 30 minutes, and 1, 3, 6, 9, 24, 32, 48, 56, 72 (PK2 and PK3 only), and 96 hours (PK2 and PK3 only).
Title
Pharmacokinetics (Pk) -Time to Maximum Concentration in Plasma (Tmax) (One-stage Clotting Assay)
Description
Tmax in hours will be defined as the time to reach Cmax. Participants in the pharmacokinetic full analysis set (PKFAS) analysis set received an initial infusion of ADVATE for pharmacokinetic analysis (PK-1) followed by a washout period and an infusion of BAX 855 for a second pharmacokinetic analysis (PK-2). After at least 50 EDs of BAX 855, participants in the PK subgroup received another infusion of BAX 855 for pharmacokinetic analysis (PK-3).
Time Frame
Within 30 minutes prior to start of infusion; and post-infusion at 10, 30 minutes, and 1, 3, 6, 9, 24, 32, 48, 56, 72 (PK2 and PK3 only), and 96 hours (PK2 and PK3 only).
Title
Change in Vital Signs From Screening - Temperature
Time Frame
Screening, week 2, week 4, exposure day 10-15, month 3, study completion/termination
Title
Change in Vital Signs From Screening - Pulse Rate
Time Frame
Screening, week 2, week 4, exposure day 10-15, month 3, study completion/termination
Title
Change in Vital Signs From Screening - Respiratory Rate
Time Frame
Screening, week 2, week 4, exposure day 10-15, month 3, study completion/termination
Title
Changes in Vital Signs From Screening - Blood Pressure
Description
Systolic Blood Pressure (SBP) Diastolic Blood Pressure (DBP)
Time Frame
Screening, week 2, week 4, exposure day 10-15, month 3, study completion/termination
Title
Changes in Clinical Chemistry Laboratory Assessments From Screening - Albumin and Protein
Time Frame
Screening, week 2, week 4, month 3, study completion/termination
Title
Changes in Clinical Chemistry Laboratory Assessments From Screening - Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase
Description
Alkaline Phosphatase (Alk Phos); Alanine Aminotransferase (Ala Amino); Aspartate Aminotransferase (Asp Amino)
Time Frame
Screening, week 2, week 4, month 3, study completion/termination
Title
Changes in Clinical Chemistry Laboratory Assessments From Screening - Bicarbonate, Chloride, Glucose, Potassium, Sodium, Blood Urea Nitrogen (BUN)
Time Frame
Screening, week 2, week 4, month 3, study completion/termination
Title
Changes in Clinical Chemistry Laboratory Assessments From Screening - Creatinine, and Bilirubin
Time Frame
Screening, week 2, week 4, month 3, study completion/termination
Title
Changes in Hematology Laboratory Assessments From Screening - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, and Leukocytes
Time Frame
Screening, week 2, week 4, month 3, study completion/termination
Title
Changes in Hematology Laboratory Assessments From Screening - Hematocrit
Time Frame
Screening, week 2, week 4, month 3, study completion/termination
Title
Changes in Hematology Laboratory Assessments From Screening - Hemoglobin
Time Frame
Screening, week 2, week 4, month 3, study completion/termination
Title
Changes in Hematology Laboratory Assessments From Screening - Erythrocytes
Time Frame
Screening, week 2, week 4, month 3, study completion/termination
Title
Changes in Lipid Panel Assessments From Screening - Cholesterol; High Density Lipoprotein (HDL); Low Density Lipoprotein (LDL); Triglycerides; and Very Low Density Lipoprotein (VLDL)
Time Frame
Screening, week 2, week 4, month 3, study completion/termination

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Main Inclusion Criteria: Participant and/or legal representative has/have voluntarily provided signed informed consent Participant is 12 to 65 years old at the time of screening Participant is male with severe hemophilia A (Factor VIII (FVIII) clotting activity < 1%) as confirmed by central laboratory at screening after the appropriate washout period or a documented FVIII clotting activity <1% Participant has been previously treated with plasma-derived FVIII concentrates or recombinant FVIII for ≥150 documented exposure days (EDs) Participant is currently receiving prophylaxis or on-demand therapy with FVIII Participant is willing and able to comply with the requirements of the protocol Main Exclusion Criteria: Participant has detectable FVIII inhibitory antibodies (≥ 0.6 Bethesda Units (BU) using the Nijmegen modification of the Bethesda assay) as confirmed by central laboratory at screening Participant has history of FVIII inhibitory antibodies (≥ 0.4 BU using the Nijmegen modification of the Bethesda assay or ≥ 0.6 BU using the Bethesda assay) at any time prior to screening Participant has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia A (eg, qualitative platelet defect or von Willebrand's disease).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
University of Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
University of Florida, College of Medicine
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Children's Healthcare of Atlanta
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Bleeding and Clotting Disorders Institute
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61614
Country
United States
Facility Name
University of Kentucky Medical Center
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40504
Country
United States
Facility Name
University of Louisville Hospital
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Tulane University Medical School
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70124
Country
United States
Facility Name
Children's Mercy Hospitals & Clinics
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
66211
Country
United States
Facility Name
Weill Cornell Medical College-New York Presbyterian Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
University of North Carolina Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
The Cleveland Clinic Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Penn State Milton S. Hershey Medical Center
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
Palmetto Health
City
Columbia
State/Province
South Carolina
ZIP/Postal Code
29203
Country
United States
Facility Name
University of Utah Health Sciences Center
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
Puget Sound Blood Group
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Royal Adelaide Hospital
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
The Alfred Hospital
City
Clayton
State/Province
Victoria
ZIP/Postal Code
3168
Country
Australia
Facility Name
Fremantle Hospital
City
Fremantle
State/Province
Western Australia
ZIP/Postal Code
6160
Country
Australia
Facility Name
Hollywood Specialist Centre
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Name
Landes-Frauen-und Kinderklinik Linz
City
Linz
ZIP/Postal Code
4020
Country
Austria
Facility Name
AKH - Medizinische Universität Wien
City
Vienna
ZIP/Postal Code
1090
Country
Austria
Facility Name
SHAT of Oncohaematology Diseases
City
Sofia
ZIP/Postal Code
1527
Country
Bulgaria
Facility Name
Fakultni nemocnice Brno
City
Brno
ZIP/Postal Code
61300
Country
Czechia
Facility Name
Fakultni nemocnice Olomouc
City
Olomouc
ZIP/Postal Code
775 20
Country
Czechia
Facility Name
Fakultni nemocnice v Motole
City
Praha 5
ZIP/Postal Code
150 06
Country
Czechia
Facility Name
Gerinnungszentrum Rhein-Ruhr
City
Duisburg
State/Province
Nordrhein Westfalen
ZIP/Postal Code
47051
Country
Germany
Facility Name
Vivantes Klinikum im Friedrichshain - Landsberger Allee
City
Berlin
ZIP/Postal Code
10249
Country
Germany
Facility Name
Universitaetsklinikum Hamburg-Eppendorf
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Werlhof-Institut MVZ
City
Hannover
ZIP/Postal Code
30159
Country
Germany
Facility Name
Rambam Health Care Campus
City
Haifa
ZIP/Postal Code
3109601
Country
Israel
Facility Name
Chaim Sheba Medical Center
City
Tel Aviv
ZIP/Postal Code
64239
Country
Israel
Facility Name
Nagoya University Hospital
City
Nagoya-shi
State/Province
Aichi-Ken
ZIP/Postal Code
466-8560
Country
Japan
Facility Name
University of Occupational and Environmental Health Hospital
City
Kitakyushu-shi
State/Province
Fukuoka-Ken
ZIP/Postal Code
807-8556
Country
Japan
Facility Name
Hiroshima University Hospital
City
Hiroshima-shi
State/Province
Hiroshima-Ken
ZIP/Postal Code
734-8551
Country
Japan
Facility Name
Hyogo College of Medicine Hospital
City
Nishinomiya-shi
State/Province
Hyogo-Ken
ZIP/Postal Code
663-8501
Country
Japan
Facility Name
St. Marianna University School of Medicine Hospital
City
Kawasaki-shi
State/Province
Kanagawa-Ken
ZIP/Postal Code
216-8511
Country
Japan
Facility Name
Nara Medical University Hospital
City
Kashihara-shi
State/Province
Nara-Ken
ZIP/Postal Code
634-8522
Country
Japan
Facility Name
Tokyo Medical University Hospital
City
Shinjuku-ku
State/Province
Tokyo-To
ZIP/Postal Code
160-0023
Country
Japan
Facility Name
Ogikubo Hospital
City
Suginami-ku
State/Province
Tokyo-To
ZIP/Postal Code
167-8515
Country
Japan
Facility Name
Chonnam National University Hwasun Hospital
City
Hwasun
State/Province
Jeollanam-do
ZIP/Postal Code
519-763
Country
Korea, Republic of
Facility Name
Pusan National University Hospital
City
Busan
ZIP/Postal Code
602-739
Country
Korea, Republic of
Facility Name
Eulji University Hospital
City
Daejeon
ZIP/Postal Code
302-120
Country
Korea, Republic of
Facility Name
Kyung hee University Hospital at Gangdong
City
Seoul
ZIP/Postal Code
134-727
Country
Korea, Republic of
Facility Name
Ulsan University Hospital
City
Ulsan
ZIP/Postal Code
682-714
Country
Korea, Republic of
Facility Name
Vilnius University Hospital Santariskiu Clinics, Public Institution
City
Vilnius
ZIP/Postal Code
08661
Country
Lithuania
Facility Name
Children's Hospital, Affiliate of Vilnius University Hospital Santariskiu Klinikos
City
Vilnius
ZIP/Postal Code
LT-08406
Country
Lithuania
Facility Name
Hospital Pulau Pinang
City
George Town
State/Province
Pulau Pinang
ZIP/Postal Code
10990
Country
Malaysia
Facility Name
Hospital Tengku Ampuan Rahimah
City
Klang
State/Province
Selangor
ZIP/Postal Code
41200
Country
Malaysia
Facility Name
Pusat Darah Negara
City
Kuala Lumpur
ZIP/Postal Code
50400
Country
Malaysia
Facility Name
Academisch Medisch Centrum
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
Facility Name
Uniwersyteckie Centrum Kliniczne
City
Gdansk
ZIP/Postal Code
80-952
Country
Poland
Facility Name
Wojewodzki Szpital Specjalistyczny im.M.Kopernika w Lodzi
City
Lodz
ZIP/Postal Code
93-510
Country
Poland
Facility Name
Sanador SRL
City
Bucuresti
ZIP/Postal Code
011026
Country
Romania
Facility Name
Hospital Universitari Son Espases
City
Palma de Mallorca
State/Province
Baleares
ZIP/Postal Code
07010
Country
Spain
Facility Name
Complejo Hospitalario Universitario A Coruña
City
A Coruña
State/Province
La Coruña
ZIP/Postal Code
15006
Country
Spain
Facility Name
Hospital Regional Universitario de Malaga
City
Malaga
State/Province
Málaga
ZIP/Postal Code
29010
Country
Spain
Facility Name
Hospital Universitari i Politecnic La Fe
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Facility Name
Skånes Universitetssjukhus, Malmö
City
Malmö
ZIP/Postal Code
20502
Country
Sweden
Facility Name
Karolinska Universitetssjukhuset, Solna
City
Stockholm
ZIP/Postal Code
17176
Country
Sweden
Facility Name
Universitatsspital Zurich
City
Zurich
ZIP/Postal Code
8091
Country
Switzerland
Facility Name
Tri-Service General Hospital
City
Taipei
ZIP/Postal Code
11490
Country
Taiwan
Facility Name
SI V.K.Gusak Emergency and Reconstructive Surgery Institute of NAMSU Center of IT
City
Donetsk
ZIP/Postal Code
83045
Country
Ukraine
Facility Name
SI Institute of Blood Pathology and Transfusion Medicine of NAMSU
City
Lviv
ZIP/Postal Code
79044
Country
Ukraine
Facility Name
Bristol Royal Hospital for Children
City
Bristol
State/Province
Avon
ZIP/Postal Code
BS2 8BJ
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
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
Royal Manchester Children's Hospital
City
Manchester
State/Province
Greater Manchester
ZIP/Postal Code
M13 9WL
Country
United Kingdom
Facility Name
Leicester Royal Infirmary
City
Leicester
State/Province
Leicestershire
ZIP/Postal Code
LE1 5WW
Country
United Kingdom
Facility Name
Churchill Hospital
City
Oxford
State/Province
Oxfordshire
ZIP/Postal Code
OX3 7LJ
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
IPD Sharing Access Criteria
IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
IPD Sharing URL
https://vivli.org/ourmember/takeda/
Citations:
PubMed Identifier
26157075
Citation
Konkle BA, Stasyshyn O, Chowdary P, Bevan DH, Mant T, Shima M, Engl W, Dyck-Jones J, Fuerlinger M, Patrone L, Ewenstein B, Abbuehl B. Pegylated, full-length, recombinant factor VIII for prophylactic and on-demand treatment of severe hemophilia A. Blood. 2015 Aug 27;126(9):1078-85. doi: 10.1182/blood-2015-03-630897. Epub 2015 Jul 8.
Results Reference
derived

Learn more about this trial

Study Investigating a PEGylated Recombinant Factor VIII (BAX 855) for Hemophilia A (PROLONG-ATE Study)

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