A Study of PEGylated Recombinant Factor VIII (BAX855) in Previously Untreated Young Children With Severe Hemophilia A
Hemophilia A
About this trial
This is an interventional treatment trial for Hemophilia A
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.
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
Experimental
Previously untreated patients (PUPs)
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.