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

NCT ID: NCT02615691

Last Updated: 2025-07-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-12
• Study Completion Date: 2024-10-29

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

PEGylated Recombinant Factor VIII

Intervention Type: BIOLOGICAL

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

ITI

Intervention Type: BIOLOGICAL

Immune tolerance induction therapy

Interventions

PEGylated Recombinant Factor VIII

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

Intervention Type: BIOLOGICAL

ITI

Immune tolerance induction therapy

Intervention Type: BIOLOGICAL

Other Intervention Names

ADYNOVATE; BAX 855; TAK-660

Eligibility Criteria

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.

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.

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.

• Maximum Eligible Age: 5 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda Development Center Americas, Inc.

INDUSTRY

Sponsor Role: collaborator

Baxalta now part of Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Phoenix Childrens Hospital

Phoenix, Arizona, United States

Kaiser Permanente Oakland M.C.

Cupertino, California, United States

Kaiser Permanente Oakland M.C.

Oakland, California, United States

Kaiser Permanente Oakland M.C.

Roseville, California, United States

UC Davis Health System

Sacramento, California, United States

Connecticut Children's Med Ctr

Hartford, Connecticut, United States

Univ Florida College Medicine

Gainesville, Florida, United States

Center for Advanced Pediatrics

Atlanta, Georgia, United States

Ann & Robert H. Lurie Children's H

Chicago, Illinois, United States

Bleeding and Clotting Dis.Inst.

Peoria, Illinois, United States

UMHS

Ann Arbor, Michigan, United States

New York Presbyterian Hospital

New York, New York, United States

Novant Health Presbyterian Medical Center

Charlotte, North Carolina, United States

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, United States

Cincinnati Children's Hospital

Cincinnati, Ohio, United States

Rainbow Babies/Childrens Htl

Cleveland, Ohio, United States

Penn State MS Hershey Med Ctr

Hershey, Pennsylvania, United States

Texas Tech University Health Sciences Center

El Paso, Texas, United States

Texas Children's Hospital

Houston, Texas, United States

Primary Children's Hospital

Salt Lake City, Utah, United States

Medizinische Universitat Wien

Vienna, , Austria

HUDERF

Brussels, , Belgium

Cliniques Uni Saint-Luc

Brussels, , Belgium

Univ. Ziekenhuis Gent Apotheek

Ghent, , Belgium

Universitair Ziekenhuis Leuven

Leuven, , Belgium

UMHAT Sv. Georgi, EAD

Plovdiv, , Bulgaria

SHAT Oncohaematology Diseases

Sofia, , Bulgaria

MHAT Sv. Marina, EAD

Varna, , Bulgaria

Kaye Edmonton Clinic

Edmonton, Alberta, Canada

McMaster Health Science

Hamilton, Ontario, Canada

Rigshospitalet Copenhagen

Copenhagen, , Denmark

Helsinki Univ Hospital

Helsinki, , Finland

CHU CAEN Hopital Cote de Nacre

Caen, Calvados, France

Essais cliniques CHU Rennes

Rennes, Ille Et Vilaine, France

Hopital Necker Enfants Malades

Paris, Paris, France

Hopital Jeanne de Flandre - CHU Lille

Lille, , France

CHU de Rouen

Rouen, , France

Werlhof-Institut GmbH

Hanover, Lower Saxony, Germany

Inst. f. Experimentelle

Bonn, , Germany

Klinik F.Haematologie,Onkologie

Düsseldorf, , Germany

Poliklinik PaediaHaematologie

Hamburg, , Germany

The University of Hong Kong Queen Mary Hospital

Hong Kong, , Hong Kong

Chinese University Of Hong Kong

Shatin, , Hong Kong

Belgyogyaszat Onkohaematologia

Budapest, , Hungary

Debreceni Egyetem

Debrece, , Hungary

Presidio Ospedaliero F. Alessi

Catania, , Italy

Azienda Ospedaliera Universitaria Careggi

Florence, , Italy

Ospedale Maggiore Policlinico

Milan, , Italy

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

Rome, , Italy

Hospital Ampang

Ampang, Kuala Lumpur, Malaysia

Hospital HRPB

Ipoh, Perak, Malaysia

Hospital Pulau Pinang

George Town, Pulau Pinang, Malaysia

Hospital Kuala Lumpur

Kuala Lumpur, , Malaysia

Hospital Umum Sarawak

Kuching, , Malaysia

Hospital Sultanah Nur Zahirah

Terengganu, , Malaysia

Universitair Medisch Centrum Groningen (UMCG)

Groningen, , Netherlands

Oslo Universitetssykehus - Rikshospitalet

Oslo, , Norway

NUS YLL School of Medicine

Singapore, , Singapore

KKH

Singapore, , Singapore

Eulji University Hospital

Daejeon, , South Korea

Severance Hospital, Yonsei

Seoul, , South Korea

Kyung Hee University Hospital

Seoul, , South Korea

Ulsan University Hospital

Ulsan, , South Korea

Hospital Univ. Son Espases

Palma de Mallorca, Balearic Islands, Spain

HOSPITAL A Coruna

A Coruña, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Univ del Rio Hortega

Valladolid, , Spain

Kaohsiung Chung- Ho Memorial Hosp

Kaohsiung City, , Taiwan

China Medical University Hospital

Taichung, , Taiwan

Taichung Veterans General

Taichung, , Taiwan

Tri-Service General Hospital

Taipei, , Taiwan

Siriraj Hospital

Bangkoknoi, Bangkok, Thailand

King Chulalongkorn Memorial

Patumwan, Bangkok, Thailand

Ramathibodi Hospital

Ratchathewi, Bangkok, Thailand

Srinagarind Hospital

Muang, Changwat Khon Kaen, Thailand

Maharaj Nakorn Chiang Mai

Muang, Chiang Mai, Thailand

Acibadem Adana Hospital

Adana, , Turkey (Türkiye)

Hacettepe Üniversitesi

Ankara, , Turkey (Türkiye)

Akdeniz Universitesi

Antalya, , Turkey (Türkiye)

Uludag Universitesi Tip Fakültesi

Bursa, , Turkey (Türkiye)

Istanbul Üniversitesi Cerrahpaşa

Istanbul, , Turkey (Türkiye)

Ege Universitesi Tip Fakultesi

Izmir, , Turkey (Türkiye)

Erciyes Univers Tip Fakultesi

Kayseri, , Turkey (Türkiye)

19 Mayis Universitesi

Samsun, , Turkey (Türkiye)

MI Cherkasy Reg Onc Dis of CRC

Cherkasy, , Ukraine

SI Institute of Blood Pathology and Transfusion Medicine of NAMSU

Lviv, , Ukraine

CI Zaporizhzhia Reg CCH of ZRC

Zaporizhzhia, , Ukraine

Royal Manchester Children's Hospital

Manchester, Greater Manchester, United Kingdom

Univ Hospital Southampton

Southampton, Hampshire, United Kingdom

Bristol Royal H. for Children

Bristol, , United Kingdom

Evelina Children's Hospital - St Thomas' Hospital

London, , United Kingdom

Countries

United States; Austria; Belgium; Bulgaria; Canada; Denmark; Finland; France; Germany; Hong Kong; Hungary; Italy; Malaysia; Netherlands; Norway; Singapore; South Korea; Spain; Taiwan; Thailand; Turkey (Türkiye); Ukraine; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 37646148 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://clinicaltrials.takeda.com/study-detail/5f6b5fc74db2bf003ab45e99

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

Other Identifiers

2015-002136-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

261203

Identifier Type: -

Identifier Source: org_study_id