NCT02210091

Brief Summary

The study purpose is:

  • To assess the incidence of FVIII inhibitory antibodies during 6 months of twice weekly prophylactic treatment with BAX 855 or 50 exposure days (EDs), whichever occurs last.
  • To compare pharmacokinetic (PK) parameters to ADVATE.
  • To assess hemostatic efficacy in prophylaxis and the treatment of bleeding episodes.
  • To evaluate safety and immunogenicity.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
75

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Oct 2014

Shorter than P25 for phase_3

Geographic Reach
11 countries

39 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 25, 2014

Completed
12 days until next milestone

First Posted

Study publicly available on registry

August 6, 2014

Completed
3 months until next milestone

Study Start

First participant enrolled

October 31, 2014

Completed
12 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 23, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 23, 2015

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

December 5, 2016

Completed
Last Updated

May 24, 2021

Status Verified

April 1, 2021

Enrollment Period

12 months

First QC Date

July 25, 2014

Results QC Date

December 2, 2016

Last Update Submit

April 30, 2021

Conditions

Outcome Measures

Primary Outcomes (1)

  • Number of Participants With Inhibitory Antibodies to Factor VIII (FVIII)

    Inhibitory antibodies to FVIII were measured using the Nijmegen modification of the Bethesda assay. Incidence of an FVIII inhibitory antibody was defined as an inhibitor level ≥0.6 Bethesda units \[BU\].

    After first exposure to BAX 855 until completion of study - approx. 6 months per participant.

Secondary Outcomes (22)

  • Annualized Bleeding Rate (ABR)

    During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last

  • Consumption of BAX 855: Number of Prophylactic Infusions Per Month Per Participant

    During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last

  • Consumption of BAX 855: Number of Prophylactic Infusions Per Year (Annualized) Per Participant

    During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last

  • Consumption of BAX 855: Weight-adjusted Dose of Prophylactic Infusions Per Month Per Participant

    During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last

  • Consumption of BAX 855: Weight-adjusted Dose of Prophylactic Infusions Per Year (Annualized) Per Participant

    During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last

  • +17 more secondary outcomes

Study Arms (2)

<6 years old

EXPERIMENTAL
Biological: Antihemophilic Factor (Recombinant) - Plasma/Albumin Free MethodBiological: PEGylated Recombinant Factor VIII

≥6 to <12 years

EXPERIMENTAL
Biological: Antihemophilic Factor (Recombinant) - Plasma/Albumin Free MethodBiological: PEGylated Recombinant Factor VIII

Interventions

Pharmacokinetic (PK) analysis of ADVATE

Also known as: ADVATE
<6 years old≥6 to <12 years

Pharmacokinetic (PK) analysis of BAX 855

Also known as: BAX 855
<6 years old≥6 to <12 years

Eligibility Criteria

AgeUp to 11 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • Severe hemophilia A (Factor VIII (FVIII) \<1%) determined by central laboratory.
  • \<12 years old at the time of screening.
  • Participants aged ≥6 to \<12 years of age have been previously treated with plasma-derived and/or recombinant Factor VIII (rFVIII) concentrate(s) for a minimum of 150 exposure days (EDs) (based on the participant's medical records).
  • Participants \<6 years of age have been previously treated with plasma-derived and/or rFVIII concentrate(s) for at least 50 EDs (based on the participant's medical records).
  • Participant is human immunodeficiency virus (HIV) negative; or HIV positive with stable disease and CD4+ count of ≥200 cells/mm\^3, as confirmed by central laboratory.
  • Participant and/or legal representative accepts prophylactic treatment over a period of 6 months.
  • Participant and/or the legal representative is willing and able to comply with the requirements of the protocol.

You may not qualify if:

  • Participant has detectable FVIII inhibitory antibodies (≥0.4 Bethesda Units (BU) using the Nijmegen modification of the Bethesda assay) as confirmed by central laboratory at screening.
  • Participant has a history of FVIII inhibitory antibodies (≥0.4 BU using the Nijmegen modification of the Bethesda assay or ≥0.6 BU using the Bethesda assay) at any time prior to screening.
  • Participant has known hypersensitivity towards mouse or hamster proteins, polyethylene glycol (PEG), or Tween 80.
  • 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's platelet count is \<100,000/μL.
  • Participant has severe chronic hepatic dysfunction (eg, ≥5 times upper limit of normal (ULN) alanine aminotransferase (ALT), as confirmed by central laboratory at screening, or a documented international normalized ratio (INR) \>1.5).
  • Participant has severe renal impairment (serum creatinine \>1.5 times ULN).
  • Participant is scheduled to receive during the course of the study, an immunomodulating drug (eg, corticosteroid agents at a dose equivalent to hydrocortisone \>10 mg/day, or α-interferon) other than anti-retroviral chemotherapy.
  • 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 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.
  • Participant 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.
  • Participant's legal representative is 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (39)

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

University of Colorado

Denver, Colorado, 80220, United States

Location

University of Florida College of Medicine

Gainesville, Florida, 32610, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Cornell University

New Hyde Park, New York, 11040, United States

Location

New York Presbyterian Hospital-Weill

New York, New York, 10065, United States

Location

Cincinnati Childrens Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Nationwide Childrens Hospital

Columbus, Ohio, 43205, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

University of Utah

Salt Lake City, Utah, 84108, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

UMHAP Sveti Georgi EAD

Plovdiv, 4000, Bulgaria

Location

Specialized Hospital for Active Treatment of Oncohematological Diseases in Children

Sofia, 1527, Bulgaria

Location

Multiprofile Hospital for Active Treatment "Sveta Marina"

Varna, 9010, Bulgaria

Location

The Chinese University of Hong Kong

Shatin, New Territories, Hong Kong

Location

Hospital Pulau Pinang

George Town, Pulau Pinang, 10450, Malaysia

Location

Hospital Umum Sarawak

Kuching, Sarawak, 93586, Malaysia

Location

Hospital Sibu

Sibu, Sarawak, 96000, Malaysia

Location

Ampang Hospital

Ampang, Selangor, 68000, Malaysia

Location

Tengku Ampian Rahimah (TAR) Hospital

Klang, Selangor, 41200, Malaysia

Location

Academic Medical Centre

Amsterdam, 1105 NZ, Netherlands

Location

Eulji University Hosptial

Seo-gu, Daejeon, 302-799, South Korea

Location

Ulsan University Hosptial

Dong-gu, Ulsan, 682-714, South Korea

Location

Severance Hospital

Seoul, 134-727, South Korea

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario La Fe

Valencia, 460026, Spain

Location

Taichung Veterans General Hospital

Taichung, Xitun District, 40705, Taiwan

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

Istanbul University Faculty of Medicine, Department of Pediatric Immunology

Cerrahpaşa, Istanbul, 34098, Turkey (Türkiye)

Location

Ankara University Medical Faculty

Ankara, 06560, Turkey (Türkiye)

Location

Akdeniz Univesity Medical Faculty

Antalya, 07059, Turkey (Türkiye)

Location

Yuzuncu Yil University Medical Faculty

Van, 65000, Turkey (Türkiye)

Location

Institute of Blood Pathology and Transfusion Medicine of Academy of Medical Sciences of Ukraine

Lviv, 79044, Ukraine

Location

Birmingham Childrens Hospital NHS Trust

Birmingham, B4 6NH, United Kingdom

Location

St. Thomas's Hospital

London, SE1 7EH, United Kingdom

Location

Great Ormond Street Hospital For Children

London, WC1N 3JH, United Kingdom

Location

Royal Manchester Children's Hospital

Manchester, M13 9WL, United Kingdom

Location

Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

Location

Related Publications (1)

  • Mullins ES, Stasyshyn O, Alvarez-Roman MT, Osman D, Liesner R, Engl W, Sharkhawy M, Abbuehl BE. Extended half-life pegylated, full-length recombinant factor VIII for prophylaxis in children with severe haemophilia A. Haemophilia. 2017 Mar;23(2):238-246. doi: 10.1111/hae.13119. Epub 2016 Nov 27.

MeSH Terms

Conditions

Hemophilia A

Interventions

Factor VIIIBAX 855

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, InheritedBlood Coagulation DisordersHematologic DiseasesHemic and Lymphatic DiseasesCoagulation Protein DisordersHemorrhagic DisordersGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Blood Coagulation FactorsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsProtein PrecursorsBiological Factors

Results Point of Contact

Title
Study Director
Organization
Shire

Study Officials

  • Study Director

    Takeda

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 25, 2014

First Posted

August 6, 2014

Study Start

October 31, 2014

Primary Completion

October 23, 2015

Study Completion

October 23, 2015

Last Updated

May 24, 2021

Results First Posted

December 5, 2016

Record last verified: 2021-04

Data Sharing

IPD Sharing
Will share

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.

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.
More information

Locations