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

NCT02615691 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: 2612032015-002136-40
• Study Type: interventional
• Target: 120
• Locations: 23 countries
• Sites: 91

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.

Conditions

Hemophilia A

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (18)

• Number of Participants With Binding Immunoglobulin G (IgG) and Immunoglobulin M (IgM) Antibodies

  Throughout Part A of the study, approximately 5 years

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  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

  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

  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)

  Throughout Part A and Part B of the study, approximately 9 years

Study Arms (1)

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.

Biological: PEGylated Recombinant Factor VIII; Biological: ITI

Interventions

PEGylated Recombinant Factor VIII BIOLOGICAL

Polyethylene glycol (PEG)-ylated full-length recombinant FVIII (rFVIII).

Also known as: ADYNOVATE, BAX 855, TAK-660

All Participants

ITI BIOLOGICAL

Immune tolerance induction therapy

All Participants

Eligibility Criteria

• Age: Up to 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Baxalta now part of Shire: lead
• Takeda Development Center Americas, Inc.: collaborator

Study Sites (91)

Phoenix Childrens Hospital

Phoenix, Arizona, 85016, United States

Location

Kaiser Permanente Oakland M.C.

Cupertino, California, 95014, United States

Location

Kaiser Permanente Oakland M.C.

Oakland, California, 94611, United States

Location

Kaiser Permanente Oakland M.C.

Roseville, California, 95661, United States

Location

UC Davis Health System

Sacramento, California, 95817, United States

Location

Connecticut Children's Med Ctr

Hartford, Connecticut, 06106, United States

Location

Univ Florida College Medicine

Gainesville, Florida, 17033-0850, United States

Location

Center for Advanced Pediatrics

Atlanta, Georgia, 30322, United States

Location

Ann & Robert H. Lurie Children's H

Chicago, Illinois, 60611-2605, United States

Location

Bleeding and Clotting Dis.Inst.

Peoria, Illinois, 61615, United States

Location

UMHS

Ann Arbor, Michigan, 48109-5008, United States

Location

New York Presbyterian Hospital

New York, New York, 10065, United States

Location

Novant Health Presbyterian Medical Center

Charlotte, North Carolina, 28204, United States

Location

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229-3039, United States

Location

Rainbow Babies/Childrens Htl

Cleveland, Ohio, 44106, United States

Location

Penn State MS Hershey Med Ctr

Hershey, Pennsylvania, 17033-0850, United States

Location

Texas Tech University Health Sciences Center

El Paso, Texas, 79905, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

Location

Medizinische Universitat Wien

Vienna, 1090, Austria

Location

HUDERF

Brussels, 1020, Belgium

Location

Cliniques Uni Saint-Luc

Brussels, 1200, Belgium

Location

Univ. Ziekenhuis Gent Apotheek

Ghent, 9000, Belgium

Location

Universitair Ziekenhuis Leuven

Leuven, 3000, Belgium

Location

UMHAT Sv. Georgi, EAD

Plovdiv, 4000, Bulgaria

Location

SHAT Oncohaematology Diseases

Sofia, 1527, Bulgaria

Location

MHAT Sv. Marina, EAD

Varna, 9010, Bulgaria

Location

Kaye Edmonton Clinic

Edmonton, Alberta, T6G 1Z1, Canada

Location

McMaster Health Science

Hamilton, Ontario, L8N 3Z5, Canada

Location

Rigshospitalet Copenhagen

Copenhagen, 2100, Denmark

Location

Helsinki Univ Hospital

Helsinki, 00290, Finland

Location

CHU CAEN Hopital Cote de Nacre

Caen, Calvados, 14033, France

Location

Essais cliniques CHU Rennes

Rennes, Ille Et Vilaine, 35033, France

Location

Hopital Necker Enfants Malades

Paris, Paris, 75743, France

Location

Hopital Jeanne de Flandre - CHU Lille

Lille, 59037, France

Location

CHU de Rouen

Rouen, 76031, France

Location

Werlhof-Institut GmbH

Hanover, Lower Saxony, 30159, Germany

Location

Inst. f. Experimentelle

Bonn, 53127, Germany

Location

Klinik F.Haematologie,Onkologie

Düsseldorf, 40225, Germany

Location

Poliklinik PaediaHaematologie

Hamburg, 20246, Germany

Location

The University of Hong Kong Queen Mary Hospital

Hong Kong, Hong Kong

Location

Chinese University Of Hong Kong

Shatin, Hong Kong

Location

Belgyogyaszat Onkohaematologia

Budapest, 1086, Hungary

Location

Debreceni Egyetem

Debrece, 4032, Hungary

Location

Presidio Ospedaliero F. Alessi

Catania, 95124, Italy

Location

Azienda Ospedaliera Universitaria Careggi

Florence, 50134, Italy

Location

Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Umberto I Pol. di Roma-Università di Roma La Sapienza

Rome, 00144, Italy

Location

Hospital Ampang

Ampang, Kuala Lumpur, 68000, Malaysia

Location

Hospital HRPB

Ipoh, Perak, 30990, Malaysia

Location

Hospital Pulau Pinang

George Town, Pulau Pinang, 10990, Malaysia

Location

Hospital Kuala Lumpur

Kuala Lumpur, 50586, Malaysia

Location

Hospital Umum Sarawak

Kuching, 93586, Malaysia

Location

Hospital Sultanah Nur Zahirah

Terengganu, 20400, Malaysia

Location

Universitair Medisch Centrum Groningen (UMCG)

Groningen, 9713 GZ, Netherlands

Location

Oslo Universitetssykehus - Rikshospitalet

Oslo, N-0372, Norway

Location

NUS YLL School of Medicine

Singapore, 117599, Singapore

Location

KKH

Singapore, 229899, Singapore

Location

Eulji University Hospital

Daejeon, 35233, South Korea

Location

Severance Hospital, Yonsei

Seoul, 03722, South Korea

Location

Kyung Hee University Hospital

Seoul, 05278, South Korea

Location

Ulsan University Hospital

Ulsan, 44033, South Korea

Location

Hospital Univ. Son Espases

Palma de Mallorca, Balearic Islands, 07120, Spain

Location

HOSPITAL A Coruna

A Coruña, 15006, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Univ del Rio Hortega

Valladolid, 47012, Spain

Location

Kaohsiung Chung- Ho Memorial Hosp

Kaohsiung City, 80756, Taiwan

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

Taichung Veterans General

Taichung, 40705, Taiwan

Location

Tri-Service General Hospital

Taipei, 11490, Taiwan

Location

Siriraj Hospital

Bangkoknoi, Bangkok, 10700, Thailand

Location

King Chulalongkorn Memorial

Patumwan, Bangkok, 10330, Thailand

Location

Ramathibodi Hospital

Ratchathewi, Bangkok, 10400, Thailand

Location

Srinagarind Hospital

Muang, Changwat Khon Kaen, 40002, Thailand

Location

Maharaj Nakorn Chiang Mai

Muang, Chiang Mai, 50200, Thailand

Location

Acibadem Adana Hospital

Adana, 1130, Turkey (Türkiye)

Location

Hacettepe Üniversitesi

Ankara, 06100, Turkey (Türkiye)

Location

Akdeniz Universitesi

Antalya, 7058, Turkey (Türkiye)

Location

Uludag Universitesi Tip Fakültesi

Bursa, 16059, Turkey (Türkiye)

Location

Istanbul Üniversitesi Cerrahpaşa

Istanbul, 34098, Turkey (Türkiye)

Location

Ege Universitesi Tip Fakultesi

Izmir, 35040, Turkey (Türkiye)

Location

Erciyes Univers Tip Fakultesi

Kayseri, 38039, Turkey (Türkiye)

Location

19 Mayis Universitesi

Samsun, 55319, Turkey (Türkiye)

Location

MI Cherkasy Reg Onc Dis of CRC

Cherkasy, 18009, Ukraine

Location

SI Institute of Blood Pathology and Transfusion Medicine of NAMSU

Lviv, 79044, Ukraine

Location

CI Zaporizhzhia Reg CCH of ZRC

Zaporizhzhia, 69063, Ukraine

Location

Royal Manchester Children's Hospital

Manchester, Greater Manchester, M13 9WL, United Kingdom

Location

Univ Hospital Southampton

Southampton, Hampshire, SO16 6YD, United Kingdom

Location

Bristol Royal H. for Children

Bristol, BS2 8AE, United Kingdom

Location

Evelina Children's Hospital - St Thomas' Hospital

London, SE1 7EH, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 37646148 DERIVED

Related Links

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

MeSH Terms

Conditions

Hemophilia A

Interventions

BAX 855

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2015
• First Posted: November 26, 2015
• Study Start: November 12, 2015
• Primary Completion: October 29, 2024
• Study Completion: October 29, 2024
• Last Updated: July 28, 2025
• Results First Posted: July 28, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.

Locations

TH (5); CA (2); DE (4); HK (2); SG (2); MY (6); NO (1); TU (8); FR (5); ES (4); AU (1); GB (4); TW (4); HU (2); BE (4); IT (4); KR (4); DK (1); FI (1); BU (3); UA (3); NL (1); US (20)