Hemophilia APhase 3NCT02615691
A Study of PEGylated Recombinant Factor VIII (BAX855) in Previously Untreated Young Children With Severe Hemophilia A
A Phase 3 study testing PEGylated Recombinant Factor VIII and ITI in people with Hemophilia A, run by Baxalta now part of Shire at 91 sites in 23 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 5 years
- Conditions the study is for
- Hemophilia A
- What is being tested?
- PEGylated Recombinant Factor VIII and ITI
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 91 sitesin 23 countries
- Study dates
- 12 Nov 2015to 29 Oct 2024
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 5 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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]).
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
91 sites in 23 countries.
91 sites in 23 countries
United States20 sites
UMHS
Ann Arbor, Michigan, 48109-5008
Center for Advanced Pediatrics
Atlanta, Georgia, 30322
Novant Health Presbyterian Medical Center
Charlotte, North Carolina, 28204
Ann & Robert H. Lurie Children's H
Chicago, Illinois, 60611-2605
Cincinnati Children's Hospital
Cincinnati, Ohio, 45229-3039
Rainbow Babies/Childrens Htl
Cleveland, Ohio, 44106
Kaiser Permanente Oakland M.C.
Cupertino, California, 95014
Texas Tech University Health Sciences Center
El Paso, Texas, 79905
Univ Florida College Medicine
Gainesville, Florida, 17033-0850
Connecticut Children's Med Ctr
Hartford, Connecticut, 06106
Penn State MS Hershey Med Ctr
Hershey, Pennsylvania, 17033-0850
Texas Children's Hospital
Houston, Texas, 77030
New York Presbyterian Hospital
New York, New York, 10065
Kaiser Permanente Oakland M.C.
Oakland, California, 94611
Bleeding and Clotting Dis.Inst.
Peoria, Illinois, 61615
Phoenix Childrens Hospital
Phoenix, Arizona, 85016
Kaiser Permanente Oakland M.C.
Roseville, California, 95661
UC Davis Health System
Sacramento, California, 95817
Primary Children's Hospital
Salt Lake City, Utah, 84113
Wake Forest Baptist Medical Center
Winston-Salem, North Carolina, 27157
Turkey (Türkiye)8 sites
Acibadem Adana Hospital
Adana, 1130
Hacettepe Üniversitesi
Ankara, 06100
Akdeniz Universitesi
Antalya, 7058
Uludag Universitesi Tip Fakültesi
Bursa, 16059
Istanbul Üniversitesi Cerrahpaşa
Istanbul, 34098
Ege Universitesi Tip Fakultesi
Izmir, 35040
Erciyes Univers Tip Fakultesi
Kayseri, 38039
19 Mayis Universitesi
Samsun, 55319
Malaysia6 sites
Hospital Ampang
Ampang, Kuala Lumpur, 68000
Hospital Pulau Pinang
George Town, Pulau Pinang, 10990
Hospital HRPB
Ipoh, Perak, 30990
Hospital Kuala Lumpur
Kuala Lumpur, 50586
Hospital Umum Sarawak
Kuching, 93586
Hospital Sultanah Nur Zahirah
Terengganu, 20400
France5 sites
CHU CAEN Hopital Cote de Nacre
Caen, Calvados, 14033
Hopital Jeanne de Flandre - CHU Lille
Lille, 59037
Hopital Necker Enfants Malades
Paris, Paris, 75743
Essais cliniques CHU Rennes
Rennes, Ille Et Vilaine, 35033
CHU de Rouen
Rouen, 76031
Thailand5 sites
Siriraj Hospital
Bangkoknoi, Bangkok, 10700
Srinagarind Hospital
Muang, Changwat Khon Kaen, 40002
Maharaj Nakorn Chiang Mai
Muang, Chiang Mai, 50200
King Chulalongkorn Memorial
Patumwan, Bangkok, 10330
Ramathibodi Hospital
Ratchathewi, Bangkok, 10400
Belgium4 sites
HUDERF
Brussels, 1020
Cliniques Uni Saint-Luc
Brussels, 1200
Univ. Ziekenhuis Gent Apotheek
Ghent, 9000
Universitair Ziekenhuis Leuven
Leuven, 3000
Germany4 sites
Inst. f. Experimentelle
Bonn, 53127
Klinik F.Haematologie,Onkologie
Düsseldorf, 40225
Poliklinik PaediaHaematologie
Hamburg, 20246
Werlhof-Institut GmbH
Hanover, Lower Saxony, 30159
Italy4 sites
Presidio Ospedaliero F. Alessi
Catania, 95124
Azienda Ospedaliera Universitaria Careggi
Florence, 50134
Ospedale Maggiore Policlinico
Milan, 20122
Umberto I Pol. di Roma-Università di Roma La Sapienza
Rome, 00144
South Korea4 sites
Eulji University Hospital
Daejeon, 35233
Severance Hospital, Yonsei
Seoul, 03722
Kyung Hee University Hospital
Seoul, 05278
Ulsan University Hospital
Ulsan, 44033
Spain4 sites
HOSPITAL A Coruna
A Coruña, 15006
Hospital Universitario La Paz
Madrid, 28046
Hospital Univ. Son Espases
Palma de Mallorca, Balearic Islands, 07120
Hospital Univ del Rio Hortega
Valladolid, 47012
Taiwan4 sites
Kaohsiung Chung- Ho Memorial Hosp
Kaohsiung City, 80756
China Medical University Hospital
Taichung, 40447
Taichung Veterans General
Taichung, 40705
Tri-Service General Hospital
Taipei, 11490
United Kingdom4 sites
Bristol Royal H. for Children
Bristol, BS2 8AE
Evelina Children's Hospital - St Thomas' Hospital
London, SE1 7EH
Royal Manchester Children's Hospital
Manchester, Greater Manchester, M13 9WL
Univ Hospital Southampton
Southampton, Hampshire, SO16 6YD
Bulgaria3 sites
UMHAT Sv. Georgi, EAD
Plovdiv, 4000
SHAT Oncohaematology Diseases
Sofia, 1527
MHAT Sv. Marina, EAD
Varna, 9010
Ukraine3 sites
MI Cherkasy Reg Onc Dis of CRC
Cherkasy, 18009
SI Institute of Blood Pathology and Transfusion Medicine of NAMSU
Lviv, 79044
CI Zaporizhzhia Reg CCH of ZRC
Zaporizhzhya, 69063
Canada2 sites
Kaye Edmonton Clinic
Edmonton, Alberta, T6G 1Z1
McMaster Health Science
Hamilton, Ontario, L8N 3Z5
Hong Kong2 sites
The University of Hong Kong Queen Mary Hospital
Hong Kong
Chinese University Of Hong Kong
Shatin
Hungary2 sites
Belgyogyaszat Onkohaematologia
Budapest, 1086
Debreceni Egyetem
Debrece, 4032
Singapore2 sites
NUS YLL School of Medicine
Singapore, 117599
KKH
Singapore, 229899
Netherlands1 site
Universitair Medisch Centrum Groningen (UMCG)
Groningen, 9713 GZ
About this study
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%)
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.
- Conditions
- Hemophilia A
- Being tested
- PEGylated Recombinant Factor VIII, ITI
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PEGylated Recombinant Factor VIIIBiological
Also called ADYNOVATE, BAX 855, TAK-660
Polyethylene glycol (PEG)-ylated full-length recombinant FVIII (rFVIII).
ITIBiological
Immune tolerance induction therapy
| Study group | Role | What they receive |
|---|---|---|
| All Participants | Experimental | 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. Receives: Biological: PEGylated Recombinant Factor VIII; Biological: ITI |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Up to 33 months in Part B of the study
Secondary outcomes (18)
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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 33 months in Part B of the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2015 (estimated)
- Study start12 Nov 2015
- Primary completion29 Oct 2024
- Study completion29 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hemophilia AStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baxalta now part of Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Takeda Development Center Americas, Inc.
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02615691
- Sponsor's protocol ID
- 261203
- Other IDs
- 2015-002136-40, 2015
- Status last verified
- Jul 2025
- First submitted
- 24 Nov 2015
- Last updated
- 28 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Sidonio RF Jr, Thompson AA, Peyvandi F, Stasyshyn O, Yeoh SL, Sosothikul D, Antmen AB, Maggiore C, Engl W, Ewenstein B, Tangada S. Immunogenicity, safety, and efficacy of rurioctocog alfa pegol in previously untreated patients with severe hemophilia A: interim results from a phase 3, prospective, multicenter, open-label study. Expert Rev Hematol. 2023 Jul-Dec;16(10):793-801. doi: 10.1080/17474086.2023.2247160. Epub 2023 Sep 7.
PubMed 37646148
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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%)
- ClinicalTrials.gov ID
- NCT02615691
- Acronym / sponsor ID
- 261203
- Conditions
- Hemophilia A
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- Baxalta now part of ShireIndustry (pharma, biotech, devices)
- Collaborators
- Takeda Development Center Americas, Inc.
- Study start
- 12 Nov 2015 (actual)
- Primary completion
- 29 Oct 2024 (actual)
- Study completion
- 29 Oct 2024 (actual)
- First posted
- 26 Nov 2015 (estimated)
- Results
- Posted 28 Jul 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All Participants | Experimental | Biological: PEGylated Recombinant Factor VIII, Biological: ITIPreviously 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. |
Who may qualify
- Ages
- Up to 5 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PEGylated Recombinant Factor VIIIAlso: ADYNOVATE, BAX 855, TAK-660Polyethylene glycol (PEG)-ylated full-length recombinant FVIII (rFVIII). | Biological | All Participants |
| ITIImmune tolerance induction therapy | Biological | All Participants |
Primary outcome
Number of Participants With FVIII Inhibitor Development
Time frame: Throughout Part A of the study, approximately 5 years
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.
Number of Participants With Success of Immune Tolerance Induction (ITI)
Time frame: Up to 33 months in Part B of the study
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.
18 secondary outcomes
Number of Participants With Binding Immunoglobulin G (IgG) and Immunoglobulin M (IgM) Antibodies
Time frame: Throughout Part A of the study, approximately 5 years
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: Throughout Part A and Part B of the study, approximately 9 years
Bleeding Episodes Categorized by Number of BAX 855 Infusions Required for Treatment
Time frame: Throughout Part A of the study, approximately 5 years
Number of Bleeds by Overall Hemostatic Efficacy Rating at 24 Hours After Initiation of Treatment
Time frame: At 24 hours after study drug administration during Part A of the study
Number of Bleeds by Overall Hemostatic Efficacy Rating at Bleed Resolution
Time frame: 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
Time frame: Throughout Part A of the study, approximately 5 years
Weight-adjusted Consumption of BAX 855: Average Number of Prophylactic Infusions
Time frame: Throughout Part A and Part B of the study, approximately 9 years
Weight-adjusted Consumption of BAX 855: Average Dose
Time frame: Throughout Part A of the study, approximately 5 years
Number of Participants by Hemostatic Efficacy Rating in Case of Surgery
Time frame: Surgery Day 0 up to postoperative Day 14 or discharge (whichever occurs first)
Blood Loss Per Participant in Case of Surgery
Time frame: Surgery Day 0 up to postoperative Day 14 or discharge (whichever occurs first)
Incremental Recovery (IR) of BAX 855
Time frame: 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
Time frame: 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
Time frame: Up to 33 months in Part B of the study
Immune Tolerance Induction (ITI) - Number of Participants With At Least One Catheter-related Complication
Time frame: 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
Time frame: Up to 33 months in Part B of the study
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37646148Sidonio RF Jr, Thompson AA, Peyvandi F, Stasyshyn O, Yeoh SL, Sosothikul D, Antmen AB, Maggiore C, Engl W, Ewenstein B, Tangada S. Immunogenicity, safety, and efficacy of rurioctocog alfa pegol in previously untreated patients with severe hemophilia A: interim results from a phase 3, prospective, multicenter, open-label study. Expert Rev Hematol. 2023 Jul-Dec;16(10):793-801. doi: 10.1080/17474086.2023.2247160. Epub 2023 Sep 7.
- To obtain more information on the study, click here/on this linkLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Takeda
91 sites in 23 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing PEGylated Recombinant Factor VIII and ITI in people with Hemophilia A, run by Baxalta now part of Shire at 91 sites in 23 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 91 sites in United States, Turkey (Türkiye), Malaysia, France, Thailand and 18 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With FVIII Inhibitor Development (time frame: Throughout Part A of the study, approximately 5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02615691, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2025.