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A Study of PEGylated Recombinant Factor VIII (BAX855) in Previously Untreated Young Children With Severe Hemophilia A

Primary Purpose

Hemophilia A

Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
PEGylated Recombinant Factor VIII
ITI
Sponsored by
Baxalta now part of Shire
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hemophilia A

Eligibility Criteria

undefined - 5 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria

  1. Participant is <6 years old at the time of screening.
  2. Participant is previously untreated with <3 exposure days (EDs) to ADVATE, BAX 855 or plasma transfusion at any time prior to screening.
  3. Participant has severe hemophilia A (Factor VIII (FVIII) <1%) as determined by the central laboratory, or a historical FVIII level <1% as determined at any local laboratory, optionally supported by an additional FVIII gene mutation consistent with severe hemophilia A.
  4. Participant is immune competent with a cluster of differentiation 4 (CD4+) count > 200 cells per cubic millimeter (mm^3), as confirmed by the central laboratory at screening.
  5. Parent or legally authorized representative is willing and able to comply with the requirements of the protocol.

Additional inclusion criteria for Part B (immune tolerance induction [ITI]).

  1. Parent or legal representative has/have voluntarily provided signed informed consent for ITI portion.
  2. Participant has a confirmed positive high titer inhibitor (> 5.00 Bethesda unit (BU)) or has a positive confirmed low titer inhibitor (greater than or equal to [>=] 0.6 BU) as determined by the central laboratory based on a second repeat blood sample with

    1. poorly controlled bleeding despite increased BAX 855 doses, or
    2. requires bypassing agents to treat bleeding.

Exclusion Criteria

  1. Participant has detectable FVIII inhibitory antibodies (>=0.6 BU using the Nijmegen modification of the Bethesda assay) as confirmed by central laboratory at screening.
  2. Participant has a history of FVIII inhibitory antibodies (>=0.6 BU using the Nijmegen modification of the Bethesda assay or the Bethesda assay) at any time prior to screening.
  3. Participant has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia A (eg, qualitative platelet defect or von Willebrand's disease).
  4. Participant has been previously treated with any type of FVIII concentrate other than ADVATE or BAX 855, or was administered ADVATE, BAX 855 or plasma transfusion for >=3 EDs at any time prior to screening.
  5. Participant receives > two EDs of ADVATE in total during the periods prior to enrollment and during the screening period, until the baseline infusion.
  6. The participant's weight is anticipated to be <5 kilogram (kg) at the baseline visit.
  7. Participant's platelet count is <100,000 per milliliter (mL).
  8. Participant has known hypersensitivity towards mouse or hamster proteins, polyethylene glycol (PEG) or Tween 80.
  9. Participant has severe chronic hepatic dysfunction (eg, >5 times upper limit of normal alanine aminotransferase [ALT], aspartate aminotransferase [AST], or a documented international normalized ratio [INR] >1.5) in his medical history or at the time of screening.
  10. Participant has severe renal impairment (serum creatinine >1.5 times the upper limit of normal).
  11. Participant has current or recent (<30 days) use of other PEGylated drugs prior to study participation or is scheduled to use such drugs during study participation.
  12. Participant is scheduled to receive during the course of the study a systemic immunomodulating drug (e.g. corticosteroid agents at a dose equivalent to hydrocortisone greater than 10 mg/day or α-interferon) other than anti-retroviral chemotherapy.
  13. Participant has participated in another clinical study involving an investigational product (IP) or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study.
  14. Parent or legally authorized representative has a medical, psychiatric, or cognitive illness or recreational drug/alcohol use that, in the opinion of the investigator, would affect participant safety or compliance.
  15. Parent, legally authorized representative or participant are a member of the team conducting this study or is in a dependent relationship with one of the study team members. Dependent relationships include close relatives (ie, children, partner/spouse, siblings, parents) as well as employees of the investigator or site personnel conducting the study.

Additional exclusion criteria for Part B (ITI)

  1. Spontaneous disappearance of the inhibitor prior to ITI.
  2. FVIII inhibitor titer >=0.6 BU is not confirmed by a second new blood sample and determined at the central laboratory.
  3. Inability or unwillingness to comply with the protocol.

Sites / Locations

  • Phoenix Childrens Hospital
  • Kaiser Permanente Oakland M.C.
  • Kaiser Permanente Oakland M.C.
  • Kaiser Permanente Oakland M.C.
  • UC Davis Health System
  • Connecticut Children's Med Ctr
  • Univ Florida College Medicine
  • Center for Advanced Pediatrics
  • Ann & Robert H. Lurie Children's H
  • Bleeding and Clotting Dis.Inst.
  • UMHS
  • New York Presbyterian Hospital
  • Novant Health Presbyterian Medical Center
  • Wake Forest Baptist Medical Center
  • Cincinnati Children's Hospital
  • Rainbow Babies/Childrens Htl
  • Penn State MS Hershey Med Ctr
  • Texas Tech University Health Sciences Center
  • Texas Children's Hospital
  • Primary Children's Hospital
  • Medizinische Universitat Wien
  • HUDERF
  • Cliniques Uni Saint-Luc
  • Univ. Ziekenhuis Gent Apotheek
  • Universitair Ziekenhuis Leuven
  • UMHAT Sv. Georgi, EAD
  • SHAT Oncohaematology Diseases
  • MHAT Sv. Marina, EAD
  • Kaye Edmonton Clinic
  • McMaster Health Science
  • Rigshospitalet Copenhagen
  • Helsinki Univ Hospital
  • CHU CAEN Hopital Cote de Nacre
  • Essais cliniques CHU Rennes
  • Hopital Necker Enfants Malades
  • Hopital Jeanne de Flandre - CHU Lille
  • CHU de Rouen
  • Werlhof-Institut GmbH
  • Inst. f. Experimentelle
  • Klinik F.Haematologie,Onkologie
  • Poliklinik PaediaHaematologie
  • The University of Hong Kong Queen Mary Hospital
  • Chinese University Of Hong Kong
  • Belgyogyaszat Onkohaematologia
  • Debreceni Egyetem
  • Presidio Ospedaliero F. Alessi
  • Azienda Ospedaliera Universitaria Careggi
  • Ospedale Maggiore Policlinico
  • Umberto I Pol. di Roma-Università di Roma La Sapienza
  • Eulji University Hospital
  • Severance Hospital, Yonsei
  • Kyung Hee University Hospital
  • Ulsan University Hospital
  • Hospital Ampang
  • Hospital HRPB
  • Hospital Pulau Pinang
  • Hospital Kuala Lumpur
  • Hospital Umum Sarawak
  • Hospital Sultanah Nur Zahirah
  • Universitair Medisch Centrum Groningen (UMCG)
  • Oslo Universitetssykehus - Rikshospitalet
  • NUS YLL School of Medicine
  • KKH
  • Hospital Univ. Son Espases
  • HOSPITAL A Coruna
  • Hospital Universitario La Paz
  • Hospital Univ del Rio Hortega
  • Kaohsiung Chung- Ho Memorial Hosp
  • China Medical University Hospital
  • Taichung Veterans General
  • Tri-Service General Hospital
  • Siriraj Hospital
  • King Chulalongkorn Memorial
  • Ramathibodi Hospital
  • Maharaj Nakorn Chiang Mai
  • Srinagarind Hospital
  • Acibadem Adana Hospital
  • Hacettepe Üniversitesi
  • Akdeniz Universitesi
  • Uludag Universitesi Tip Fakültesi
  • Istanbul Üniversitesi Cerrahpaşa
  • Ege Universitesi Tip Fakultesi
  • Erciyes Univers Tip Fakultesi
  • 19 Mayis Universitesi
  • MI Cherkasy Reg Onc Dis of CRC
  • SI Institute of Blood Pathology and Transfusion Medicine of NAMSU
  • CI Zaporizhzhia Reg CCH of ZRC
  • Royal Manchester Children's Hospital
  • Univ Hospital Southampton
  • Bristol Royal H. for Children
  • Evelina Children's Hospital - St Thomas' Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Previously untreated patients (PUPs)

Arm Description

Part A (Main Study): Participants age <3 years and not experienced two joint bleeds will receive on- demand treatment of 10-80 international unit per kilogram (IU/kg) of BAX 855 intravenously depending on the severity of the bleeding episode and age <3 years or after a maximum of two joint bleeds will receive prophylaxis treatment with dose of 25-80 IU/kg of BAX855 IV (based on investigator discretion) once weekly for up to 100 EDs. Part A (Surgery): In participants, the administration of BAX 855 will be individualized based on the participants IR and half-life. For major surgery to achieve the target level of 80-100% FVIII in plasma of normal FVIII level and for minor surgery >=30-60% FVIII levels for dental or other invasive surgery. Part B (Immune tolerance induction [ITI]): Participants will receive prophylaxis treatment of 100-200 IU/kg BAX 855 IV daily or 50 IU/kg three time in a week and will be reduced to twice weekly to maintain FVIII trough level of 1% for further 3 months.

Outcomes

Primary Outcome Measures

Number of Participants With FVIII Inhibitor Development
Number of participants who develop an inhibitor (at any time) confirmed by a central laboratory based on a second repeat blood sample draw within 2 weeks of site notification of an inhibitor and all participants who not developed an inhibitor and has greater than or equal to (>=) 100 exposure doses (EDs) when the sample for the last valid inhibitor test will be drawn.
Success Rate of Immune Tolerance Induction (ITI)
Success is defined as 1) a persistently negative inhibitor titer less than (<) 0.6 Bethesda unit (BU), 2) FVIII IR >=66% of the baseline value following a wash-out period of 84-96 hours, and 3) a FVIII half-life of >=6 hours.

Secondary Outcome Measures

Binding Immunoglobulin G (IgG) and Immunoglobulin M (IgM) Antibodies
Binding IgG and IgM antibodies to Factor VIII (FVIII), Factor VIII-Polyethylene glycol (PEG-FVIII) and Polyethylene glycol (PEG).
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is defined as any untoward medical occurrence in a participant administered an IP that does not necessarily have a causal relationship with the treatment. A SAE is any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to investigational product or not and at any dose) which results in death, is life-threatening, requires inpatient hospitalization, prolongation of hospitalization, is an important medical event. Number of participants with AEs and SAEs in both part A and part B will be assessed.
Number of Participants With Clinically Significant Changes in Vital Signs
Vital signs will be assessed based on body temperature, respiratory rate, blood pressure, and heart rate.
Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters
Clinical laboratory parameters includes hematology and clinical chemistry. Changes in laboratory values may be considered as AE if they are judged to be clinically significant.
Annualized Bleeding Rate (ABR) for Prophylactic and On-demand Treatment
ABR is assessed based upon each individual bleeding episode. A bleeding episode is defined as subjective (pain consistent with a joint bleed) or objective evidence of bleeding which may or may not require treatment with FVIII. Bleeding occurring at multiple locations related to the same injury (example, knee and ankle bleed following a fall) will be counted as a single bleeding episode. Total annualized bleed rate (spontaneous and traumatic bleeding episodes) will be reported.
Number of BAX 855 Infusions Needed for the Treatment of Bleeding Episodes
A bleeding episode is defined as subjective (pain consistent with a joint bleed) or objective evidence of bleeding which may or may not require treatment with FVIII. The number of BAX 855 infusions needed for each bleeding episode is determined by the participant, caregiver, clinician treating the participant, and is based upon the participant's response to treatment, using the Efficacy Rating Scale for Treatment of Bleeding Episodes.
Number of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Initiation of Treatment
The participant or caregiver rated the overall treatment response using a 4-point efficacy rating scale as Excellent: Full relief of pain and cessation of objective signs of bleeding after a single infusion and no additional infusion is required for the control of bleeding; Good: Definite pain relief and/or improvement in signs of bleeding after a single infusion and 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 and required more than 1 infusion for complete resolution and None: No improvement or condition worsens
Number of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Bleed Resolution
The participant or caregiver rated the overall treatment response using a 4-point efficacy rating scale as Excellent: Full relief of pain and cessation of objective signs of bleeding after a single infusion and no additional infusion is required for the control of bleeding; Good: Definite pain relief and/or improvement in signs of bleeding after a single infusion and 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 and required more than 1 infusion for complete resolution and None: No improvement or condition worsens.
Number of Participants With Weight-adjusted Consumption of BAX 855
Weight-adjusted consumption of BAX 855 will be determined based upon the record in participants diaries of the actual amount of BAX 855 infused, indication (treatment of bleeding episode, prophylaxis,surgery) and the participants weight, as measured in the clinic.
Number of Infusions During Weight-adjusted Consumption of BAX 855
The number of BAX 855 infusions needed for each bleeding episode is determined by the participant, caregiver, clinician treating the participant, and is based upon the participant's response to treatment, using the Efficacy Rating Scale for Treatment of Bleeding Episodes.
Number of Participants With Hemostatic Efficacy in Case of Surgery
The hemostatic efficacy will be assessed during and after any surgical or invasive procedures, and overall as a perioperative assessment.
Blood Loss Per Participant in Case of Surgery
The intraoperative blood loss will be measured by determining the volume of blood and fluid removal through suction into the collection container (waste box and/or cell saver) and the estimated blood loss into swabs and towels during the procedure, per the anesthesiologist's record. Post-operatively, blood loss will be determined by the drainage volume collected, which will mainly consist of drainage fluid via vacuum or gravity drain, as applicable.
Incremental Recovery (IR) of BAX 855
BAX 855 will be administered in participants for the determination of FVIII IR at the study site at baseline and every study visit other than study visits.
Half-life (T1/2) of BAX 855
The Half-life to determine FVIII half-life is an optional assessment that will be performed at baseline, Visit 1, or Visit 2.
Immune Tolerance Induction (ITI) - Rate of Partial Success and Failure of ITI
Partial success defined as which meet two of following criteria, 1) inhibitor titer <0.6 BU (confirmed by a central laboratory with a second blood specimen obtained within 2 months), 2) FVIII in vivo recovery >=66% of baseline value (confirmed within a two month period), and 3) FVIII half-life >=6 hours. Failure defined as the failure to meet the criteria for partial success.
Immune Tolerance Induction (ITI) - Annualized Bleeding Rate (ABR)
ABR is assessed based upon each individual bleeding episode. A bleeding episode is defined as subjective (pain consistent with a joint bleed) or objective evidence of bleeding which may or may not require treatment with FVIII. Bleeding occurring at multiple locations related to the same injury (example, knee and ankle bleed following a fall) will be counted as a single bleeding episode. Total annualized bleed rate (spontaneous and traumatic bleeding episodes) will be reported.
Immune Tolerance Induction (ITI) - Weight-adjusted Consumption of BAX 855 for Each ITI Regimen Employed
Weight-adjusted consumption of BAX 855 will be determined based upon the record in participant's diaries of the actual amount of BAX 855 infused, indication (treatment of bleeding episode, prophylaxis) and the participant's weight, as measured in the clinic.
Immune Tolerance Induction (ITI) - Catheter-related Complications
The frequency per subject and per subject-year of catheter-related complications will be calculated.
Immune Tolerance Induction (ITI) - Binding Immunoglobulin G (IgG) and Immunoglobulin M (IgM) Antibodies
Binding IgG and IgM antibodies to Factor VIII (FVIII), Factor VIII-Polyethylene glycol (PEG-FVIII) and Polyethylene glycol (PEG).

Full Information

First Posted
November 24, 2015
Last Updated
September 8, 2023
Sponsor
Baxalta now part of Shire
Collaborators
Takeda Development Center Americas, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02615691
Brief Title
A Study of PEGylated Recombinant Factor VIII (BAX855) in Previously Untreated Young Children With Severe Hemophilia A
Official Title
Phase 3, Prospective, Multi-center, Open Label Study to Investigate Safety, Immunogenicity and Hemostatic Efficacy of PEGylated Factor VIII (BAX 855) in Previously Untreated Patients (PUPs) < 6 Years With Severe Hemophilia A (FVIII < 1%)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 12, 2015 (Actual)
Primary Completion Date
October 31, 2024 (Anticipated)
Study Completion Date
October 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Baxalta now part of Shire
Collaborators
Takeda Development Center Americas, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study is for young children with severe hemophilia A who have previously not been treated with BAX855 or other FVIII concentrates. The main aim of the study is to check for side effects from treatment with BAX855. This includes the buildup of antibodies against FVIII which may stop BAX855 from working properly. Another aim is to learn how well BAX855 controls bleeding. In this study, the children can receive BAX855 either as preventative treatment (prophylaxis), or as needed to treat bleeding (on-demand). In case a participant develops antibodies, treatment will be provided as part of the study.

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 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
120 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Previously untreated patients (PUPs)
Arm Type
Experimental
Arm Description
Part A (Main Study): Participants age <3 years and not experienced two joint bleeds will receive on- demand treatment of 10-80 international unit per kilogram (IU/kg) of BAX 855 intravenously depending on the severity of the bleeding episode and age <3 years or after a maximum of two joint bleeds will receive prophylaxis treatment with dose of 25-80 IU/kg of BAX855 IV (based on investigator discretion) once weekly for up to 100 EDs. Part A (Surgery): In participants, the administration of BAX 855 will be individualized based on the participants IR and half-life. For major surgery to achieve the target level of 80-100% FVIII in plasma of normal FVIII level and for minor surgery >=30-60% FVIII levels for dental or other invasive surgery. Part B (Immune tolerance induction [ITI]): Participants will receive prophylaxis treatment of 100-200 IU/kg BAX 855 IV daily or 50 IU/kg three time in a week and will be reduced to twice weekly to maintain FVIII trough level of 1% for further 3 months.
Intervention Type
Biological
Intervention Name(s)
PEGylated Recombinant Factor VIII
Other Intervention Name(s)
ADYNOVATE, BAX 855, TAK-660
Intervention Description
Polyethylene glycol (PEG)-ylated full-length recombinant FVIII (rFVIII).
Intervention Type
Biological
Intervention Name(s)
ITI
Intervention Description
Immune tolerance induction therapy
Primary Outcome Measure Information:
Title
Number of Participants With FVIII Inhibitor Development
Description
Number of participants who develop an inhibitor (at any time) confirmed by a central laboratory based on a second repeat blood sample draw within 2 weeks of site notification of an inhibitor and all participants who not developed an inhibitor and has greater than or equal to (>=) 100 exposure doses (EDs) when the sample for the last valid inhibitor test will be drawn.
Time Frame
Throughout Part A of the study, approximately 5 years
Title
Success Rate of Immune Tolerance Induction (ITI)
Description
Success is defined as 1) a persistently negative inhibitor titer less than (<) 0.6 Bethesda unit (BU), 2) FVIII IR >=66% of the baseline value following a wash-out period of 84-96 hours, and 3) a FVIII half-life of >=6 hours.
Time Frame
Up to 33 months
Secondary Outcome Measure Information:
Title
Binding Immunoglobulin G (IgG) and Immunoglobulin M (IgM) Antibodies
Description
Binding IgG and IgM antibodies to Factor VIII (FVIII), Factor VIII-Polyethylene glycol (PEG-FVIII) and Polyethylene glycol (PEG).
Time Frame
Throughout Part A of the study, approximately 5 years
Title
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
An AE is defined as any untoward medical occurrence in a participant administered an IP that does not necessarily have a causal relationship with the treatment. A SAE is any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to investigational product or not and at any dose) which results in death, is life-threatening, requires inpatient hospitalization, prolongation of hospitalization, is an important medical event. Number of participants with AEs and SAEs in both part A and part B will be assessed.
Time Frame
Throughout Part A and Part B of the study, approximately 7 years
Title
Number of Participants With Clinically Significant Changes in Vital Signs
Description
Vital signs will be assessed based on body temperature, respiratory rate, blood pressure, and heart rate.
Time Frame
Throughout Part A and Part B of the study, approximately 7 years
Title
Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters
Description
Clinical laboratory parameters includes hematology and clinical chemistry. Changes in laboratory values may be considered as AE if they are judged to be clinically significant.
Time Frame
Throughout Part A and Part B of the study, approximately 7 years
Title
Annualized Bleeding Rate (ABR) for Prophylactic and On-demand Treatment
Description
ABR is assessed based upon each individual bleeding episode. A bleeding episode is defined as subjective (pain consistent with a joint bleed) or objective evidence of bleeding which may or may not require treatment with FVIII. Bleeding occurring at multiple locations related to the same injury (example, knee and ankle bleed following a fall) will be counted as a single bleeding episode. Total annualized bleed rate (spontaneous and traumatic bleeding episodes) will be reported.
Time Frame
Throughout Part A of the study, approximately 5 years
Title
Number of BAX 855 Infusions Needed for the Treatment of Bleeding Episodes
Description
A bleeding episode is defined as subjective (pain consistent with a joint bleed) or objective evidence of bleeding which may or may not require treatment with FVIII. The number of BAX 855 infusions needed for each bleeding episode is determined by the participant, caregiver, clinician treating the participant, and is based upon the participant's response to treatment, using the Efficacy Rating Scale for Treatment of Bleeding Episodes.
Time Frame
Throughout Part A of the study, approximately 5 years
Title
Number of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Initiation of Treatment
Description
The participant or caregiver rated the overall treatment response using a 4-point efficacy rating scale as Excellent: Full relief of pain and cessation of objective signs of bleeding after a single infusion and no additional infusion is required for the control of bleeding; Good: Definite pain relief and/or improvement in signs of bleeding after a single infusion and 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 and required more than 1 infusion for complete resolution and None: No improvement or condition worsens
Time Frame
24 hours after study drug administration
Title
Number of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Bleed Resolution
Description
The participant or caregiver rated the overall treatment response using a 4-point efficacy rating scale as Excellent: Full relief of pain and cessation of objective signs of bleeding after a single infusion and no additional infusion is required for the control of bleeding; Good: Definite pain relief and/or improvement in signs of bleeding after a single infusion and 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 and required more than 1 infusion for complete resolution and None: No improvement or condition worsens.
Time Frame
From start of study treatment up to bleed resolution (approximately 5 years)
Title
Number of Participants With Weight-adjusted Consumption of BAX 855
Description
Weight-adjusted consumption of BAX 855 will be determined based upon the record in participants diaries of the actual amount of BAX 855 infused, indication (treatment of bleeding episode, prophylaxis,surgery) and the participants weight, as measured in the clinic.
Time Frame
Throughout Part A of the study, approximately 5 years
Title
Number of Infusions During Weight-adjusted Consumption of BAX 855
Description
The number of BAX 855 infusions needed for each bleeding episode is determined by the participant, caregiver, clinician treating the participant, and is based upon the participant's response to treatment, using the Efficacy Rating Scale for Treatment of Bleeding Episodes.
Time Frame
Throughout Part A of the study, approximately 5 years
Title
Number of Participants With Hemostatic Efficacy in Case of Surgery
Description
The hemostatic efficacy will be assessed during and after any surgical or invasive procedures, and overall as a perioperative assessment.
Time Frame
Surgery Day 0 up to postoperative Day 14 or discharge (whichever occurs first)
Title
Blood Loss Per Participant in Case of Surgery
Description
The intraoperative blood loss will be measured by determining the volume of blood and fluid removal through suction into the collection container (waste box and/or cell saver) and the estimated blood loss into swabs and towels during the procedure, per the anesthesiologist's record. Post-operatively, blood loss will be determined by the drainage volume collected, which will mainly consist of drainage fluid via vacuum or gravity drain, as applicable.
Time Frame
Surgery Day 0 up to postoperative Day 14 or discharge (whichever occurs first)
Title
Incremental Recovery (IR) of BAX 855
Description
BAX 855 will be administered in participants for the determination of FVIII IR at the study site at baseline and every study visit other than study visits.
Time Frame
Pre-infusion within 30 minutes; and post-infusion at 15-30 minutes and 24-48 hours
Title
Half-life (T1/2) of BAX 855
Description
The Half-life to determine FVIII half-life is an optional assessment that will be performed at baseline, Visit 1, or Visit 2.
Time Frame
Pre-infusion, Post-infusion: 15-30 minutes and 24-48 hours
Title
Immune Tolerance Induction (ITI) - Rate of Partial Success and Failure of ITI
Description
Partial success defined as which meet two of following criteria, 1) inhibitor titer <0.6 BU (confirmed by a central laboratory with a second blood specimen obtained within 2 months), 2) FVIII in vivo recovery >=66% of baseline value (confirmed within a two month period), and 3) FVIII half-life >=6 hours. Failure defined as the failure to meet the criteria for partial success.
Time Frame
Up to 33 months
Title
Immune Tolerance Induction (ITI) - Annualized Bleeding Rate (ABR)
Description
ABR is assessed based upon each individual bleeding episode. A bleeding episode is defined as subjective (pain consistent with a joint bleed) or objective evidence of bleeding which may or may not require treatment with FVIII. Bleeding occurring at multiple locations related to the same injury (example, knee and ankle bleed following a fall) will be counted as a single bleeding episode. Total annualized bleed rate (spontaneous and traumatic bleeding episodes) will be reported.
Time Frame
Up to 33 months
Title
Immune Tolerance Induction (ITI) - Weight-adjusted Consumption of BAX 855 for Each ITI Regimen Employed
Description
Weight-adjusted consumption of BAX 855 will be determined based upon the record in participant's diaries of the actual amount of BAX 855 infused, indication (treatment of bleeding episode, prophylaxis) and the participant's weight, as measured in the clinic.
Time Frame
Up to 33 months
Title
Immune Tolerance Induction (ITI) - Catheter-related Complications
Description
The frequency per subject and per subject-year of catheter-related complications will be calculated.
Time Frame
Up to 33 months
Title
Immune Tolerance Induction (ITI) - Binding Immunoglobulin G (IgG) and Immunoglobulin M (IgM) Antibodies
Description
Binding IgG and IgM antibodies to Factor VIII (FVIII), Factor VIII-Polyethylene glycol (PEG-FVIII) and Polyethylene glycol (PEG).
Time Frame
Up to 33 months

10. Eligibility

Sex
All
Maximum Age & Unit of Time
5 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Participant is <6 years old at the time of screening. Participant is previously untreated with <3 exposure days (EDs) to ADVATE, BAX 855 or plasma transfusion at any time prior to screening. Participant has severe hemophilia A (Factor VIII (FVIII) <1%) as determined by the central laboratory, or a historical FVIII level <1% as determined at any local laboratory, optionally supported by an additional FVIII gene mutation consistent with severe hemophilia A. Participant is immune competent with a cluster of differentiation 4 (CD4+) count > 200 cells per cubic millimeter (mm^3), as confirmed by the central laboratory at screening. Parent or legally authorized representative is willing and able to comply with the requirements of the protocol. Additional inclusion criteria for Part B (immune tolerance induction [ITI]). Parent or legal representative has/have voluntarily provided signed informed consent for ITI portion. Participant has a confirmed positive high titer inhibitor (> 5.00 Bethesda unit (BU)) or has a positive confirmed low titer inhibitor (greater than or equal to [>=] 0.6 BU) as determined by the central laboratory based on a second repeat blood sample with poorly controlled bleeding despite increased BAX 855 doses, or requires bypassing agents to treat bleeding. Exclusion Criteria Participant has detectable FVIII inhibitory antibodies (>=0.6 BU using the Nijmegen modification of the Bethesda assay) as confirmed by central laboratory at screening. Participant has a history of FVIII inhibitory antibodies (>=0.6 BU using the Nijmegen modification of the Bethesda assay or 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). Participant has been previously treated with any type of FVIII concentrate other than ADVATE or BAX 855, or was administered ADVATE, BAX 855 or plasma transfusion for >=3 EDs at any time prior to screening. Participant receives > two EDs of ADVATE in total during the periods prior to enrollment and during the screening period, until the baseline infusion. The participant's weight is anticipated to be <5 kilogram (kg) at the baseline visit. Participant's platelet count is <100,000 per milliliter (mL). Participant has known hypersensitivity towards mouse or hamster proteins, polyethylene glycol (PEG) or Tween 80. Participant has severe chronic hepatic dysfunction (eg, >5 times upper limit of normal alanine aminotransferase [ALT], aspartate aminotransferase [AST], or a documented international normalized ratio [INR] >1.5) in his medical history or at the time of screening. Participant has severe renal impairment (serum creatinine >1.5 times the upper limit of normal). Participant has current or recent (<30 days) use of other PEGylated drugs prior to study participation or is scheduled to use such drugs during study participation. Participant is scheduled to receive during the course of the study a systemic immunomodulating drug (e.g. corticosteroid agents at a dose equivalent to hydrocortisone greater than 10 mg/day or α-interferon) other than anti-retroviral chemotherapy. Participant has participated in another clinical study involving an investigational product (IP) or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study. Parent or legally authorized representative has a medical, psychiatric, or cognitive illness or recreational drug/alcohol use that, in the opinion of the investigator, would affect participant safety or compliance. Parent, legally authorized representative or participant are a member of the team conducting this study or is in a dependent relationship with one of the study team members. Dependent relationships include close relatives (ie, children, partner/spouse, siblings, parents) as well as employees of the investigator or site personnel conducting the study. Additional exclusion criteria for Part B (ITI) Spontaneous disappearance of the inhibitor prior to ITI. FVIII inhibitor titer >=0.6 BU is not confirmed by a second new blood sample and determined at the central laboratory. Inability or unwillingness to comply with the protocol.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
Phoenix Childrens Hospital
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85016
Country
United States
Facility Name
Kaiser Permanente Oakland M.C.
City
Cupertino
State/Province
California
ZIP/Postal Code
95014
Country
United States
Facility Name
Kaiser Permanente Oakland M.C.
City
Oakland
State/Province
California
ZIP/Postal Code
94611
Country
United States
Facility Name
Kaiser Permanente Oakland M.C.
City
Roseville
State/Province
California
ZIP/Postal Code
95661
Country
United States
Facility Name
UC Davis Health System
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Connecticut Children's Med Ctr
City
Hartford
State/Province
Connecticut
ZIP/Postal Code
06106
Country
United States
Facility Name
Univ Florida College Medicine
City
Gainesville
State/Province
Florida
ZIP/Postal Code
17033-0850
Country
United States
Facility Name
Center for Advanced Pediatrics
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Ann & Robert H. Lurie Children's H
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611-2605
Country
United States
Facility Name
Bleeding and Clotting Dis.Inst.
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61615
Country
United States
Facility Name
UMHS
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109-5008
Country
United States
Facility Name
New York Presbyterian Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Novant Health Presbyterian Medical Center
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
Wake Forest Baptist Medical Center
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
Cincinnati Children's Hospital
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229-3039
Country
United States
Facility Name
Rainbow Babies/Childrens Htl
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Penn State MS Hershey Med Ctr
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033-0850
Country
United States
Facility Name
Texas Tech University Health Sciences Center
City
El Paso
State/Province
Texas
ZIP/Postal Code
79905
Country
United States
Facility Name
Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Primary Children's Hospital
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84113
Country
United States
Facility Name
Medizinische Universitat Wien
City
Vienna
ZIP/Postal Code
1090
Country
Austria
Facility Name
HUDERF
City
Bruxelles
ZIP/Postal Code
1020
Country
Belgium
Facility Name
Cliniques Uni Saint-Luc
City
Bruxelles
ZIP/Postal Code
1200
Country
Belgium
Facility Name
Univ. Ziekenhuis Gent Apotheek
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Universitair Ziekenhuis Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
UMHAT Sv. Georgi, EAD
City
Plovdiv
ZIP/Postal Code
4000
Country
Bulgaria
Facility Name
SHAT Oncohaematology Diseases
City
Sofia
ZIP/Postal Code
1527
Country
Bulgaria
Facility Name
MHAT Sv. Marina, EAD
City
Varna
ZIP/Postal Code
9010
Country
Bulgaria
Facility Name
Kaye Edmonton Clinic
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z1
Country
Canada
Facility Name
McMaster Health Science
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 3Z5
Country
Canada
Facility Name
Rigshospitalet Copenhagen
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Facility Name
Helsinki Univ Hospital
City
Helsinki
ZIP/Postal Code
00290
Country
Finland
Facility Name
CHU CAEN Hopital Cote de Nacre
City
Caen cedex 9
State/Province
Calvados
ZIP/Postal Code
14033
Country
France
Facility Name
Essais cliniques CHU Rennes
City
Rennes cedex 09
State/Province
Ille Et Vilaine
ZIP/Postal Code
35033
Country
France
Facility Name
Hopital Necker Enfants Malades
City
Paris cedex 15
State/Province
Paris
ZIP/Postal Code
75743
Country
France
Facility Name
Hopital Jeanne de Flandre - CHU Lille
City
Lille Cedex
ZIP/Postal Code
59037
Country
France
Facility Name
CHU de Rouen
City
ROUEN Cedex
ZIP/Postal Code
76031
Country
France
Facility Name
Werlhof-Institut GmbH
City
Hannover
State/Province
Niedersachsen
ZIP/Postal Code
30159
Country
Germany
Facility Name
Inst. f. Experimentelle
City
Bonn
ZIP/Postal Code
53127
Country
Germany
Facility Name
Klinik F.Haematologie,Onkologie
City
Duesseldorf
ZIP/Postal Code
40225
Country
Germany
Facility Name
Poliklinik PaediaHaematologie
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
The University of Hong Kong Queen Mary Hospital
City
Hong Kong
Country
Hong Kong
Facility Name
Chinese University Of Hong Kong
City
Shatin
Country
Hong Kong
Facility Name
Belgyogyaszat Onkohaematologia
City
Budapest
ZIP/Postal Code
1086
Country
Hungary
Facility Name
Debreceni Egyetem
City
Debrece
ZIP/Postal Code
4032
Country
Hungary
Facility Name
Presidio Ospedaliero F. Alessi
City
Catania
ZIP/Postal Code
95124
Country
Italy
Facility Name
Azienda Ospedaliera Universitaria Careggi
City
Firenze
ZIP/Postal Code
50134
Country
Italy
Facility Name
Ospedale Maggiore Policlinico
City
Milano
ZIP/Postal Code
20122
Country
Italy
Facility Name
Umberto I Pol. di Roma-Università di Roma La Sapienza
City
Rome
ZIP/Postal Code
00144
Country
Italy
Facility Name
Eulji University Hospital
City
Daejeon
ZIP/Postal Code
35233
Country
Korea, Republic of
Facility Name
Severance Hospital, Yonsei
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Kyung Hee University Hospital
City
Seoul
ZIP/Postal Code
05278
Country
Korea, Republic of
Facility Name
Ulsan University Hospital
City
Ulsan
ZIP/Postal Code
44033
Country
Korea, Republic of
Facility Name
Hospital Ampang
City
Ampang
State/Province
Kuala Lumpur
ZIP/Postal Code
68000
Country
Malaysia
Facility Name
Hospital HRPB
City
Ipoh
State/Province
Perak
ZIP/Postal Code
30990
Country
Malaysia
Facility Name
Hospital Pulau Pinang
City
Georgetown
State/Province
Pulau Pinang
ZIP/Postal Code
10990
Country
Malaysia
Facility Name
Hospital Kuala Lumpur
City
Kuala Lumpur
ZIP/Postal Code
50586
Country
Malaysia
Facility Name
Hospital Umum Sarawak
City
Kuching
ZIP/Postal Code
93586
Country
Malaysia
Facility Name
Hospital Sultanah Nur Zahirah
City
Terengganu
ZIP/Postal Code
20400
Country
Malaysia
Facility Name
Universitair Medisch Centrum Groningen (UMCG)
City
Groningen
ZIP/Postal Code
9713 GZ
Country
Netherlands
Facility Name
Oslo Universitetssykehus - Rikshospitalet
City
Oslo
ZIP/Postal Code
N-0372
Country
Norway
Facility Name
NUS YLL School of Medicine
City
Singapore
ZIP/Postal Code
117599
Country
Singapore
Facility Name
KKH
City
Singapore
ZIP/Postal Code
229899
Country
Singapore
Facility Name
Hospital Univ. Son Espases
City
Palma de Mallorca
State/Province
Baleares
ZIP/Postal Code
07120
Country
Spain
Facility Name
HOSPITAL A Coruna
City
A Coruna
ZIP/Postal Code
15006
Country
Spain
Facility Name
Hospital Universitario La Paz
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Hospital Univ del Rio Hortega
City
Valladolid
ZIP/Postal Code
47012
Country
Spain
Facility Name
Kaohsiung Chung- Ho Memorial Hosp
City
Kaohsiung
ZIP/Postal Code
80756
Country
Taiwan
Facility Name
China Medical University Hospital
City
Taichung
ZIP/Postal Code
40447
Country
Taiwan
Facility Name
Taichung Veterans General
City
Taichung
ZIP/Postal Code
40705
Country
Taiwan
Facility Name
Tri-Service General Hospital
City
Taipei City
ZIP/Postal Code
11490
Country
Taiwan
Facility Name
Siriraj Hospital
City
Bangkoknoi
State/Province
Bangkok
ZIP/Postal Code
10700
Country
Thailand
Facility Name
King Chulalongkorn Memorial
City
Patumwan
State/Province
Bangkok
ZIP/Postal Code
10330
Country
Thailand
Facility Name
Ramathibodi Hospital
City
Ratchathewi
State/Province
Bangkok
ZIP/Postal Code
10400
Country
Thailand
Facility Name
Maharaj Nakorn Chiang Mai
City
Muang
State/Province
Chiang Mai
ZIP/Postal Code
50200
Country
Thailand
Facility Name
Srinagarind Hospital
City
Muang
State/Province
Khon Kaen
ZIP/Postal Code
40002
Country
Thailand
Facility Name
Acibadem Adana Hospital
City
Adana
ZIP/Postal Code
1130
Country
Turkey
Facility Name
Hacettepe Üniversitesi
City
Ankara
ZIP/Postal Code
06100
Country
Turkey
Facility Name
Akdeniz Universitesi
City
Antalya
ZIP/Postal Code
7058
Country
Turkey
Facility Name
Uludag Universitesi Tip Fakültesi
City
Bursa
ZIP/Postal Code
16059
Country
Turkey
Facility Name
Istanbul Üniversitesi Cerrahpaşa
City
Istanbul
ZIP/Postal Code
34098
Country
Turkey
Facility Name
Ege Universitesi Tip Fakultesi
City
Izmir
ZIP/Postal Code
35040
Country
Turkey
Facility Name
Erciyes Univers Tip Fakultesi
City
Kayseri
ZIP/Postal Code
38039
Country
Turkey
Facility Name
19 Mayis Universitesi
City
Samsun
ZIP/Postal Code
55319
Country
Turkey
Facility Name
MI Cherkasy Reg Onc Dis of CRC
City
Cherkasy
ZIP/Postal Code
18009
Country
Ukraine
Facility Name
SI Institute of Blood Pathology and Transfusion Medicine of NAMSU
City
Lviv
ZIP/Postal Code
79044
Country
Ukraine
Facility Name
CI Zaporizhzhia Reg CCH of ZRC
City
Zaporizhzhia
ZIP/Postal Code
69063
Country
Ukraine
Facility Name
Royal Manchester Children's Hospital
City
Manchester
State/Province
Greater Manchester
ZIP/Postal Code
M13 9WL
Country
United Kingdom
Facility Name
Univ Hospital Southampton
City
Southampton
State/Province
Hampshire
ZIP/Postal Code
SO16 6YD
Country
United Kingdom
Facility Name
Bristol Royal H. for Children
City
Bristol
ZIP/Postal Code
BS2 8AE
Country
United Kingdom
Facility Name
Evelina Children's Hospital - St Thomas' Hospital
City
London
ZIP/Postal Code
SE1 7EH
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
Links:
URL
https://clinicaltrials.takeda.com/study-detail/5f6b5fc74db2bf003ab45e99
Description
To obtain more information on the study, click here/on this link

Learn more about this trial

A Study of PEGylated Recombinant Factor VIII (BAX855) in Previously Untreated Young Children With Severe Hemophilia A

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