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

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%)

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.

Study Overview

• Status: Completed
• Conditions: Hemophilia A
• Intervention / Treatment: Biological: PEGylated Recombinant Factor VIII; Biological: ITI

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Medizinische Universitat Wien
• Belgium
  • Bruxelles, Belgium, 1020
    • Huderf
  • Bruxelles, Belgium, 1200
    • Cliniques Uni Saint-Luc
  • Gent, Belgium, 9000
    • Univ. Ziekenhuis Gent Apotheek
  • Leuven, Belgium, 3000
    • Universitair Ziekenhuis Leuven
• Bulgaria
  • Plovdiv, Bulgaria, 4000
    • UMHAT Sv. Georgi, EAD
  • Sofia, Bulgaria, 1527
    • SHAT Oncohaematology Diseases
  • Varna, Bulgaria, 9010
    • MHAT Sv. Marina, EAD
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z1
      • Kaye Edmonton Clinic
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster Health Science
• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet Copenhagen
• Finland
  • Helsinki, Finland, 00290
    • Helsinki Univ Hospital
• France
  • Lille Cedex, France, 59037
    • Hopital Jeanne de Flandre - CHU Lille
  • ROUEN Cedex, France, 76031
    • CHU de Rouen
  • Calvados
    • Caen cedex 9, Calvados, France, 14033
      • CHU CAEN Hopital Cote de Nacre
  • Ille Et Vilaine
    • Rennes cedex 09, Ille Et Vilaine, France, 35033
      • Essais cliniques CHU Rennes
  • Paris
    • Paris cedex 15, Paris, France, 75743
      • Hopital Necker Enfants Malades
• Germany
  • Bonn, Germany, 53127
    • Inst. f. Experimentelle
  • Duesseldorf, Germany, 40225
    • Klinik F.Haematologie,Onkologie
  • Hamburg, Germany, 20246
    • Poliklinik PaediaHaematologie
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30159
      • Werlhof-Institut GmbH
• Hong Kong
  • Hong Kong, Hong Kong
    • The University of Hong Kong Queen Mary Hospital
  • Shatin, Hong Kong
    • Chinese University of Hong Kong
• Hungary
  • Budapest, Hungary, 1086
    • Belgyogyaszat Onkohaematologia
  • Debrece, Hungary, 4032
    • Debreceni Egyetem
• Italy
  • Catania, Italy, 95124
    • Presidio Ospedaliero F. Alessi
  • Firenze, Italy, 50134
    • Azienda Ospedaliera Universitaria Careggi
  • Milano, Italy, 20122
    • Ospedale Maggiore Policlinico
  • Rome, Italy, 00144
    • Umberto I Pol. di Roma-Università di Roma La Sapienza
• Korea, Republic of
  • Daejeon, Korea, Republic of, 35233
    • Eulji University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei
  • Seoul, Korea, Republic of, 05278
    • Kyung Hee University Hospital
  • Ulsan, Korea, Republic of, 44033
    • Ulsan University Hospital
• Malaysia
  • Kuala Lumpur, Malaysia, 50586
    • Hospital Kuala Lumpur
  • Kuching, Malaysia, 93586
    • Hospital Umum Sarawak
  • Terengganu, Malaysia, 20400
    • Hospital Sultanah Nur Zahirah
  • Kuala Lumpur
    • Ampang, Kuala Lumpur, Malaysia, 68000
      • Hospital Ampang
  • Perak
    • Ipoh, Perak, Malaysia, 30990
      • Hospital HRPB
  • Pulau Pinang
    • Georgetown, Pulau Pinang, Malaysia, 10990
      • Hospital Pulau Pinang
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Universitair Medisch Centrum Groningen (UMCG)
• Norway
  • Oslo, Norway, N-0372
    • Oslo Universitetssykehus - Rikshospitalet
• Singapore
  • Singapore, Singapore, 117599
    • NUS YLL School of Medicine
  • Singapore, Singapore, 229899
    • KKH
• Spain
  • A Coruna, Spain, 15006
    • Hospital A Coruña
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Valladolid, Spain, 47012
    • Hospital Univ del Rio Hortega
  • Baleares
    • Palma de Mallorca, Baleares, Spain, 07120
      • Hospital Univ. Son Espases
• Taiwan
  • Kaohsiung, Taiwan, 80756
    • Kaohsiung Chung- Ho Memorial Hosp
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Taichung, Taiwan, 40705
    • Taichung Veterans General
  • Taipei City, Taiwan, 11490
    • Tri-Service General Hospital
• Thailand
  • Bangkok
    • Bangkoknoi, Bangkok, Thailand, 10700
      • Siriraj Hospital
    • Patumwan, Bangkok, Thailand, 10330
      • King Chulalongkorn Memorial
    • Ratchathewi, Bangkok, Thailand, 10400
      • Ramathibodi Hospital
  • Chiang Mai
    • Muang, Chiang Mai, Thailand, 50200
      • Maharaj Nakorn Chiang Mai
  • Khon Kaen
    • Muang, Khon Kaen, Thailand, 40002
      • Srinagarind Hospital
• Turkey
  • Adana, Turkey, 1130
    • Acibadem Adana Hospital
  • Ankara, Turkey, 06100
    • Hacettepe Universitesi
  • Antalya, Turkey, 7058
    • Akdeniz Universitesi
  • Bursa, Turkey, 16059
    • Uludag Universitesi Tip Fakultesi
  • Istanbul, Turkey, 34098
    • Istanbul Universitesi Cerrahpasa
  • Izmir, Turkey, 35040
    • Ege Universitesi Tip Fakultesi
  • Kayseri, Turkey, 38039
    • Erciyes Univers Tip Fakultesi
  • Samsun, Turkey, 55319
    • 19 Mayis Universitesi
• Ukraine
  • Cherkasy, Ukraine, 18009
    • MI Cherkasy Reg Onc Dis of CRC
  • Lviv, Ukraine, 79044
    • SI Institute of Blood Pathology and Transfusion Medicine of NAMSU
  • Zaporizhzhia, Ukraine, 69063
    • CI Zaporizhzhia Reg CCH of ZRC
• United Kingdom
  • Bristol, United Kingdom, BS2 8AE
    • Bristol Royal H. for Children
  • London, United Kingdom, SE1 7EH
    • Evelina Children's Hospital - St Thomas' Hospital
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom, M13 9WL
      • Royal Manchester Children's Hospital
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • Univ Hospital Southampton
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Childrens Hospital
  • California
    • Cupertino, California, United States, 95014
      • Kaiser Permanente Oakland M.C.
    • Oakland, California, United States, 94611
      • Kaiser Permanente Oakland M.C.
    • Roseville, California, United States, 95661
      • Kaiser Permanente Oakland M.C.
    • Sacramento, California, United States, 95817
      • UC Davis Health System
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Connecticut Children's Med Ctr
  • Florida
    • Gainesville, Florida, United States, 17033-0850
      • Univ Florida College Medicine
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Center for Advanced Pediatrics
  • Illinois
    • Chicago, Illinois, United States, 60611-2605
      • Ann & Robert H. Lurie Children's H
    • Peoria, Illinois, United States, 61615
      • Bleeding and Clotting Dis.Inst.
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-5008
      • UMHS
  • New York
    • New York, New York, United States, 10065
      • New York Presbyterian Hospital
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Novant Health Presbyterian Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229-3039
      • Cincinnati Children's Hospital
    • Cleveland, Ohio, United States, 44106
      • Rainbow Babies/Childrens Htl
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033-0850
      • Penn State MS Hershey Med Ctr
  • Texas
    • El Paso, Texas, United States, 79905
      • Texas Tech University Health Sciences Center
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Primary Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 5 years (Child)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: All Participants; Previously Untreated Patients (PUPs) < 6 years of age with severe hemophilia A (FVIII < 1%) and < 3 exposure days (EDs) to ADVATE, BAX 855 or plasma transfusion were enrolled in a single arm group. Part A (Main Study): Participants age <3 years - who had not experienced two joint bleeds received on-demand treatment of 10-80 international units per kilogram (IU/kg) intravenously (IV) depending on the severity of the bleeding episode; and - who experienced maximum of two joint bleeds received prophylaxis treatment with dose of 25-80 IU/kg of BAX 855 IV (based on investigator discretion) once weekly for up to 100 EDs. Part B (Immune tolerance induction [ITI] Portion): Participants who met the pre-defined Part B treatment criteria entered Part B of the study for ITI. Participants either received prophylaxis treatment of BAX 855 low dose 50 IU/kg IV, three times a week or high dose 100-200 IU/kg IV, daily at discretion of the investigator according to the institution's standard of care.

Biological: PEGylated Recombinant Factor VIII; Polyethylene glycol (PEG)-ylated full-length recombinant FVIII (rFVIII).; Other Names: BAX 855; ADYNOVATE; TAK-660; Biological: ITI; Immune tolerance induction therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With FVIII Inhibitor Development	Number of participants who developed 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 had not developed an inhibitor and had greater than or equal to (>=) 100 EDs when the sample for the last valid inhibitor test was drawn.	Throughout Part A of the study, approximately 5 years
Number of Participants With Success 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.	Up to 33 months in Part B of the study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Binding Immunoglobulin G (IgG) and Immunoglobulin M (IgM) Antibodies	Binding IgG and IgM antibodies to FVIII , Factor VIII-Polyethylene glycol (PEG-FVIII) and Polyethylene glycol (PEG) was assessed. A participant that received on-demand treatment first and then moved to prophylaxis treatment was counted for both on-demand and prophylaxis regimens. A participant that started with prophylaxis treatment was counted only for the prophylaxis regimen even if the participant received on-demand treatment while on the prophylaxis regimen. Visits and their approximate time in weeks after baseline visit for individual participants: Visit 1(Week 5), Visit 2 (Week 10), Visit 3 (Week 15), Visit 4 (Week 20), Visit 5 (Week 30), Visit 6 (Week 40), Visit 7 (Week 55), Visit 8 (Week 75) and Study Completion Visit (Weeks 100-110).	Throughout Part A of the study, approximately 5 years
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 investigational product (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 were assessed. A participant that received on-demand treatment first and then moved to prophylaxis treatment was counted for both on-demand and prophylaxis regimens. A participant that started with prophylaxis treatment was counted only for the prophylaxis regimen even if the participant received on-demand treatment while on the prophylaxis regimen.	Throughout Part A and Part B of the study, approximately 9 years
Number of Participants With At Least One Clinically Significant Changes in Vital Signs	Vital signs were assessed based on body temperature, respiratory rate, blood pressure, and heart rate.	Throughout Part A and Part B of the study, approximately 9 years
Number of Participants With At Least One Clinically Significant Changes in Clinical Laboratory Parameters	Clinical laboratory parameters included hematology and clinical chemistry. Changes in laboratory values could be considered as AE if they were judged to be clinically significant.	Throughout Part A and Part B of the study, approximately 9 years
Annualized Bleeding Rate (ABR) for Prophylactic and On-demand Treatment and Immune Tolerance Induction (ITI)	ABR was assessed based upon each individual bleeding episode. A bleeding episode was 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) was counted as a single bleeding episode. Mean total annualized bleed rate is reported. A participant that received on-demand treatment first and then moved to prophylaxis treatment was counted for both on-demand and prophylaxis regimens. A participant that started with prophylaxis treatment was counted only for the prophylaxis regimen even if the participant received on-demand treatment while on the prophylaxis regimen.	Throughout Part A and Part B of the study, approximately 9 years
Bleeding Episodes Categorized by Number of BAX 855 Infusions Required for Treatment	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 was 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 are categorized by number of infusions required to treat the bleeding episodes. A participant that received on-demand treatment first and then moved to prophylaxis treatment was counted for both on-demand and prophylaxis regimens. A participant that started with prophylaxis treatment was counted only for the prophylaxis regimen even if the participant received on-demand treatment while on the prophylaxis regimen.	Throughout Part A of the study, approximately 5 years
Number of Bleeds by Overall Hemostatic Efficacy Rating at 24 Hours After Initiation of Treatment	The participant or caregiver rated overall treatment response using a 4-point efficacy rating scale as Excellent:Full relief of pain & cessation of objective signs of bleeding after single infusion & no additional infusion is required for the control of bleeding; Good:Definite pain relief &/or improvement in signs of bleeding after single infusion & possibly requires more than 1 infusion for complete resolution; Fair:Probable &/or slight relief of pain & slight improvement in signs of bleeding after single infusion & required more than 1 infusion for complete resolution & None:No improvement or condition worsens.Number of bleeds with each efficacy rating are reported.Participant that received on-demand treatment first & then moved to prophylaxis treatment was counted for both on-demand & prophylaxis regimens.Participant that started with prophylaxis treatment was counted only for the prophylaxis regimen even if the participant received on-demand treatment while on prophylaxis regimen.	At 24 hours after study drug administration during Part A of the study
Number of Bleeds by Overall Hemostatic Efficacy Rating at Bleed Resolution	The participant or caregiver rated overall treatment response using a 4-point efficacy rating scale as Excellent:Full relief of pain & cessation of objective signs of bleeding after single infusion & no additional infusion is required for the control of bleeding; Good:Definite pain relief &/or improvement in signs of bleeding after a single infusion & possibly requires more than 1 infusion for complete resolution; Fair:Probable &/or slight relief of pain & slight improvement in signs of bleeding after single infusion & required more than 1 infusion for complete resolution & None:No improvement or condition worse.Number of bleeds with each efficacy rating are reported.Participant that received on-demand treatment first & then moved to prophylaxis treatment was counted for both on-demand & prophylaxis regimens.Participant that started with prophylaxis treatment was counted only for prophylaxis regimen even if the participant received on-demand treatment while on prophylaxis regimen.	From start of study treatment up to bleed resolution throughout Part A of the study (up to approximately 5 years)
Weight-adjusted Consumption of BAX 855: Average Prophylactic Dose	Weight-adjusted consumption of BAX 855 was determined based upon the record in participants diaries of the actual amount of BAX 855 infused as measured in the clinic. Average dose per prophylactic infusion, per month and per year are reported as categories.	Throughout Part A of the study, approximately 5 years
Weight-adjusted Consumption of BAX 855: Average Number of Prophylactic Infusions	Weight-adjusted consumption of BAX 855 was determined based upon the record in participants diaries of the actual number of BAX 855 infusions as measured in the clinic. Average number of infusions per month and year are reported as categories.	Throughout Part A and Part B of the study, approximately 9 years
Weight-adjusted Consumption of BAX 855: Average Dose	Weight-adjusted consumption of BAX 855 was determined based upon the record in participants diaries of the actual amount of BAX 855 infused as measured in the clinic. Average dose to treat bleeding episode and average FVIII inhibitor treatment Dose [IU/kg] per Week, Month and per Year are reported as categories. A participant that received on-demand treatment first and then moved to prophylaxis treatment was counted for both on-demand and prophylaxis regimens. A participant that started with prophylaxis treatment was counted only for the prophylaxis regimen even if the participant received on-demand treatment while on the prophylaxis regimen.	Throughout Part A of the study, approximately 5 years
Number of Participants by Hemostatic Efficacy Rating in Case of Surgery	Hemostatic efficacy was assessed during & after any surgical or invasive procedures,& overall as a perioperative assessment.Operating surgeon assessed hemostatic efficacy compared to that expected for the type of procedure performed in non-hemophilic population,prior to discharge from recovery room(intraoperative),on postoperative Day 1 & at discharge or 14 days post-surgery(perioperative).Participants rated efficacy using following ratings:1.Excellent:Postoperative blood loss was ≤100% than expected;2.Good:Postoperative blood loss was up to 50% more (101-150%) than expected;3.Fair:Postoperative blood loss was more than 50% (>150%) of that expected;4.None:Significant postoperative bleeding that was result of inadequate therapeutic response despite proper dosing,necessitating rescue therapy.Perioperative ratings also considered amount of blood components required for transfusions compared to expected.Participant-provided ratings for each of the assessments are reported as categories.	Surgery Day 0 up to postoperative Day 14 or discharge (whichever occurs first)
Blood Loss Per Participant in Case of Surgery	The intraoperative blood loss was 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 was determined by the drainage volume collected, which mainly consisted of drainage fluid via vacuum or gravity drain, as applicable. The assessment was done for the intra-operative time period (prior to discharge from recovery room) and for the post-operative time period (from completion of the procedure until approximately 24 hours post-surgery).	Surgery Day 0 up to postoperative Day 14 or discharge (whichever occurs first)
Incremental Recovery (IR) of BAX 855	BAX 855 was administered in participants for the determination of FVIII IR at study site at baseline & every study visit other than study visits at 5 EDs, 15 EDs & 30 EDs. FVIII assays were done using following methods:1-stage clotting FVIII activity & FVIII chromogenic activity. Data is reported for each of these methods as categories per visit. Study Completion assessment was conducted at end of the Main Study & again at end of the ITI portion. Thus, more number of participants were analyzed at study completion visit than those who actually completed the overall study. IR is reported as a ratio of (IU/deciliter [dL])/(IU/kg), calculated as: IR = (Cmax- (C pre-infusion)) / (IU/kg), where C=concentration. Visits and their approximate time in weeks after baseline visit for individual participants: Visit 1 (Week 5), Visit 2 (Week 10), Visit 3 (Week 15), Visit 4 (Week 20), Visit 5 (Week 30), Visit 6 (Week 40), Visit 7 (Week 55), Visit 8 (Week 75) & Study Completion Visit (Weeks 100-110).	Baseline up to Study Completion (Up to 5 years in Part A and up to 3.5 years in Part B)
Half-life (T1/2) of BAX 855	The Half-life to determine FVIII half-life was an optional assessment that was planned to be performed at baseline, Visit 1, or Visit 2.	Pre-infusion, Post-infusion: 15-30 minutes and 24-48 hours at Baseline
Immune Tolerance Induction (ITI) - Number of Participants With 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.	Up to 33 months in Part B of the study
Immune Tolerance Induction (ITI) - Number of Participants With At Least One Catheter-related Complication	Number of participants with catheter-related complications are reported.	Up to 33 months in Part B of the study
Immune Tolerance Induction (ITI) - Number of Participants With 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) are reported as categories per visit.	Up to 33 months in Part B of the study

Collaborators and Investigators

• Sponsor: Baxalta now part of Shire
• Collaborators: Takeda Development Center Americas, Inc.
• Investigators: Study Director: Study Director, Takeda

Publications and helpful links

Helpful Links

• To obtain more information on the study, click here/on this link

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2015
• Primary Completion (Actual): October 29, 2024
• Study Completion (Actual): October 29, 2024

Study Registration Dates

• First Submitted: November 24, 2015
• First Submitted That Met QC Criteria: November 24, 2015
• First Posted (Estimated): November 26, 2015

Study Record Updates

• Last Update Posted (Actual): July 28, 2025
• Last Update Submitted That Met QC Criteria: July 25, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemophilia A; Coagulants; BAX 855; Factor VIII
• Other Study ID Numbers: 261203; 2015-002136-40 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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 Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No