BAX 855 PK-guided Dosing

NCT02585960 | Completed Phase 3 Results

• 2 other identifiers: 2613032014-005477-37
• Study Type: interventional
• Target: 135
• Locations: 21 countries
• Sites: 82

Brief Summary

1. 1.To compare the efficacy and safety of pharmacokinetic (PK)-guided treatment with BAX 855 targeting FVIII trough levels of 1-3% and approximately 10% (8-12%)
2. 2.To further characterize pharmacokinetic (PK) and pharmacodynamic (PD) parameters of BAX 855

Conditions

Hemophilia A

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With a Total Annualized Bleeding Rate (ABR) of Zero for Second Six Months

  Annualized bleeding rate was determined by dividing the number of bleeds by observation period in years.

  Day 183 to Day 364 (6 months)

Secondary Outcomes (25)

• Total Annualized Bleeding Rate for Second Six Months

  Day 183 to Day 364 (6 months)

• Annualized Spontaneous Bleeding Rate for Second Six Months

  Day 183 to Day 364 (6 months)

• Annualized Traumatic Bleeding Rate for Second Six Months

  Day 183 to Day 364 (6 months)

• Annualized Joint Bleeding Rate (AJBR) for Second Six Months

  Day 183 to Day 364 (6 months)

• Total Weight-adjusted Consumption of BAX 855

  From start of study treatment up to 12 months (completion or termination)

Study Arms (3)

Pharmacokinetic (PK) evaluation of BAX 855

EXPERIMENTAL

Participants will first undergo an initial pharmacokinetic (PK) assessment. Following the PK assessment participants will be randomized to one of 2 dosing regimens.

Biological: PEGylated Recombinant Factor VIII

FVIII trough target 1-3%

EXPERIMENTAL

Standard treatment arm - PK-guided dosing schedule to achieve a Factor VIII (FVIII) trough of 1-3%

Biological: PEGylated Recombinant Factor VIII

FVIII trough target 8-12%

EXPERIMENTAL

Intensified treatment arm - PK-guided dosing schedule to achieve a Factor VIII (FVIII) trough of 8-12%

Biological: PEGylated Recombinant Factor VIII

Interventions

PEGylated Recombinant Factor VIII BIOLOGICAL

Pharmacokinetic (PK) evaluation

Also known as: BAX855, BAX 855

Pharmacokinetic (PK) evaluation of BAX 855

Eligibility Criteria

• Age: 12 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants transitioning from another BAX 855 study who meet ALL of the following criteria are eligible for this study:
• Participant has completed the end of study visit of a BAX 855 study or is transitioning from the ongoing Baxalta Continuation Study 261302.
• Participant is either receiving on-demand treatment or prophylactic treatment with BAX 855 and had an Annual Bleed Rate (ABR) of ≥ 2 documented and treated during the past 12 months.
• Participant is human immunodeficiency virus negative (HIV-); or HIV+ with stable disease and CD4+ count ≥ 200 cells/mm\^3, as confirmed by central laboratory.
• Participant is willing and able to comply with the requirements of the protocol.
• Newly recruited participants (ie not transitioning from another BAX 855 study) including BAX855 naïve participants who meet ALL of the following criteria are eligible for this study:
• Participant has severe hemophilia A (FVIII clotting activity \< 1%) as confirmed by central laboratory OR by historically documented FVIII clotting activity performed by a certified clinical laboratory, optionally supported by a FVIII gene mutation consistent with severe hemophilia A
• Participant has been previously treated with plasma-derived FVIII concentrates or recombinant FVIII for ≥ 150 documented exposure days (EDs)
• Participant is either receiving on-demand treatment or prophylactic treatment and had an annual bleeding rate of ≥ 2 documented and treated during the past 12 months.
• Participant has a Karnofsky performance score of ≥ 60 at screening
• Participant is HIV-; or HIV+ with stable disease and CD4+ count ≥ 200 cells/mm\^3, as confirmed by central laboratory at screening
• Participant is hepatitis C virus negative (HCV-) by antibody (if positive, additional PCR testing will be performed), as confirmed by central laboratory at screening; or HCV+ with chronic stable hepatitis
• If female of childbearing potential, participant presents with a negative urine pregnancy test and agrees to employ adequate birth control measures for the duration of the study
• Participant is willing and able to comply with the requirements of the protocol.

You may not qualify if:

• Participants transitioning from another BAX 855 study who meet ANY of the following criteria are not eligible for this study:
• Participant has developed a confirmed inhibitory antibody to FVIII with a titer of ≥ 0.6 BU using the Nijmegen modification of the Bethesda assay as determined at the central laboratory during the course of the previous BAX 855 study.
• Participant has been diagnosed with an acquired hemostatic defect other than hemophilia A.
• The participant's weight is \< 35 kg or \> 100 kg.
• Participant's platelet count is \< 100,000/mL.
• Participant has an abnormal renal function (serum creatinine \> 1.5 times the upper limit of normal).
• Participant has active hepatic disease with alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels ≥ 5 times the upper limit of normal.
• Participant is scheduled to receive 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 during the study.
• Participant has a clinically significant medical, psychiatric, or cognitive illness, or recreational drug/alcohol use that, in the opinion of the investigator, would affect participant's safety or compliance.
• Participant is planning to take part in any other clinical study during the course of the study.
• Participant 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.
• Newly recruited participants (ie not transitioning from another BAX 855 study) who meet ANY of the following criteria are not eligible for this study:
• 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 confirmed FVIII inhibitors with a titer ≥ 0.6 Bethesda Units (BU) (as determined by the Nijmegen modification of the Bethesda assay or the assay employed with the respective cut-off in the local laboratory) 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).

Sponsors & Collaborators

• Baxalta now part of Shire: lead
• Baxalta Innovations GmbH, now part of Shire: collaborator

Study Sites (83)

Phoenix Childrens Hospital

Phoenix, Arizona, 85016-7710, United States

Location

Arizona Hemophilia & Thrombosis Center, located within The University of Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

University of Florida College of Medicine

Gainesville, Florida, 32610, United States

Location

Emory University-ECC

Atlanta, Georgia, 30322, United States

Location

University of Kentucky Medical Center

Lexington, Kentucky, 40504, United States

Location

University of Louisville KCPCRU

Louisville, Kentucky, 40202, United States

Location

Tulane University

New Orleans, Louisiana, 70112, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198-5456, United States

Location

Gulf States Hemophilia Centre

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

University of Washington

Seattle, Washington, 98104, United States

Location

Royal Brisbane Women's Hospital

Herston, Queensland, 4006, Australia

Location

The Perth Blood Institute

Nedlands, Western Australia, 6009, Australia

Location

AKH - Medizinische Universität Wien

Vienna, 1090, Austria

Location

UMHAT "Sv. Georgi", EAD

Plovdiv, 4002, Bulgaria

Location

UMHAT 'Tsaritsa Yoanna - ISUL', EAD

Sofia, 1527, Bulgaria

Location

MHAT 'Sv. Marina', EAD, Clinic of Clinical Hematology

Varna, 9010, Bulgaria

Location

CHU Nice- Service hematologie

Nice, Alpes Maritimes, 06200, France

Location

Hôpital Morvan

Brest, Finistere, 29609, France

Location

CHU Rennes - Hopital Pontchaillou

Rennes, Ille Et Vilaine, 35033, France

Location

CHU de Caen - Hôpital Côte de Nacre

Caen, 14003, France

Location

CHU Charles Nicolle

Rouen, 76031, France

Location

HZRM Hamophilie Zentrum Rhein Main GmbH

Mörfelden-Walldorf, Hesse, 65446, Germany

Location

Inst. f. Experimentelle Hamatologie u. Transfusionsmedizin

Bonn, North Rhine-Westphalia, 53127, Germany

Location

COAGULATION RESEARCH CENTRE GmbH

Duisburg, North Rhine-Westphalia, 47051, Germany

Location

Hamophiliezentrum/Gerinnungssprechstunde

Berlin, 10249, Germany

Location

MVZ Labor Dr. Reising-Ackermann

Leipzig, 04289, Germany

Location

University of Hong Kong

Hong Kong, Hong Kong

Location

Prince of Wales Hospital

Shatin, 00000, Hong Kong

Location

Magyar Honvedseg EK

Budapest, 1134, Hungary

Location

DE OEC Belgyógyászati Int

Debrecen, 4032, Hungary

Location

PTE ÁOK

Pécs, 7624, Hungary

Location

Chaim Sheba Medical Center

Tel Litwinsky, 5262000, Israel

Location

UOC Ematologia, Azienda ULSS 8 Asolo, Regione Veneto

Castelfranco Veneto, Treviso, 31033, Italy

Location

Presidio Osped. Ferrarotto

Catania, 90124, Italy

Location

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

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

Roma, 00144, Italy

Location

Fondazione Policlinico Universitario A. Gemelli

Roma, 00168, Italy

Location

AOU Citta della Salute e della Scienza - Presidio Molinette

Torino, 10126, Italy

Location

ULSS n. 6 "Vicenza"

Vicenza, 36100, Italy

Location

Hospital Ampang

Ampang, Kuala Lumpur, 68000, Malaysia

Location

Hospital Queen Elizabeth

Kota Kinabalu, Sabah, 88586, Malaysia

Location

Hospital Kuala Lumpur

Kuala Lumpur, 50586, Malaysia

Location

Hospital Melaka

Malacca, 75400, Malaysia

Location

Hospital Pulau Pinang

Pulau Pinang, 10450, Malaysia

Location

Oslo Universitetssykehus HF

Oslo, 0372, Norway

Location

Wojewodzki Szpital Specjalistyczny im. Mikolaja Kopernika, Klinika Hematologii

Lodz, 93-510, Poland

Location

Alvamed

Poznan, 61-828, Poland

Location

Instytut Hematologii Ii Transfuzjologii

Warsaw, 02-776, Poland

Location

SP Szpital Kliniczny Nr 1 we Wroclawiu

Wroclaw, 50-367, Poland

Location

Spitalul Clinic Judetean de Urgenta Brasov

Brasov, 500365, Romania

Location

Institutul Oncologic ClNa.

Cluj-Napoca, 400124, Romania

Location

National University Hospital

Singapore, 119074, Singapore

Location

Singapore General Hospital- Parent

Singapore, 169608, Singapore

Location

KK Women's And Children's Hospital

Singapore, 229899, Singapore

Location

Hospital Universitari Son Espases

Palma de Mallorca, Balearic Islands, 07010, Spain

Location

Complejo Hospitalario Universitario A Coruña

A Coruña, La Coruña, 15006, Spain

Location

Hospital Regional Universitario de Malaga

Málaga, Málaga, 29010, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Sahlgrenska Universitetssjukhuset

Gothenburg, S-41345, Sweden

Location

Karolinska Universitetssjukhuset

Stockholm, 17176, Sweden

Location

Universitätsspital Zürich

Zurich, 8091, Switzerland

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

Tri-Service General Hospital

Taipei, 11490, Taiwan

Location

Acibadem Hastanesi

Adana, 01130, Turkey (Türkiye)

Location

Akdeniz University

Antalya, 07070, Turkey (Türkiye)

Location

Istanbul University

Istanbul, 34098, Turkey (Türkiye)

Location

Ege University

Izmir, 35040, Turkey (Türkiye)

Location

NChSH Okhmatdyt of MoHU Center of Children Oncohematology and Bone Marrow Transplantation

Kyiv, 1135, Ukraine

Location

Kyiv CCH #9 Dept of Surgery City SPC of Diagnostics & Treatment of Patients with HP

Kyiv, 4112, Ukraine

Location

SI Institute of Blood Pathology and Transfusion Medicine of NAMSU

Lviv, 79044, Ukraine

Location

M.V. Sklifosovskyi Poltava RCH Dept of Gematology HSEIU Ukrainian Medical Stomatological Academy

Poltava, 36011, Ukraine

Location

Bristol Royal Hospital for Children

Bristol, Avon, BS2 8BJ, United Kingdom

Location

Royal Free Hospital

London, Greater London, NW3 2QG, United Kingdom

Location

Royal Manchester Children's Hospital

Manchester, Greater Manchester, M13 9WL, United Kingdom

Location

Southampton General Hospital

Southampton, Hampshire, SO16 6YD, United Kingdom

Location

Leicester Royal Infirmary

Leicester, Leicestershire, LE1 5WW, United Kingdom

Location

Churchill Hospital

Oxford, Oxfordshire, OX3 7LJ, United Kingdom

Location

University Hospital of Wales

Cardiff, West Glamorgan, CF14 4XN, United Kingdom

Location

Related Publications (3)

• Escuriola-Ettingshausen C, Klamroth R, Escobar M, Stasyshyn O, Tangada S, Engl W, Honauer I, Lee HY, Chowdary P, Windyga J. Targeting an elevated FVIII level using personalized rurioctocog alfa pegol prophylaxis in specific patient populations with hemophilia A: post hoc subanalysis of the randomized, phase 3 PROPEL study. Ther Adv Hematol. 2023 Jul 15;14:20406207231178596. doi: 10.1177/20406207231178596. eCollection 2023.

  PMID: 37465396 DERIVED

• Sun SX, Crawford S. Microsimulation to compare activity-related bleed risks between pharmacokinetic-guided rurioctocog alfa pegol prophylaxis and emicizumab. Expert Rev Hematol. 2023 Mar;16(3):205-211. doi: 10.1080/17474086.2023.2162498. Epub 2023 Jan 18.

  PMID: 36655343 DERIVED

• Klamroth R, Windyga J, Radulescu V, Collins PW, Stasyshyn O, Ibrahim HM, Engl W, Tangada SD, Savage W, Ewenstein B. Rurioctocog alfa pegol PK-guided prophylaxis in hemophilia A: results from the phase 3 PROPEL study. Blood. 2021 Apr 1;137(13):1818-1827. doi: 10.1182/blood.2020005673.

  PMID: 33150384 DERIVED

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: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

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: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2015
• First Posted: October 26, 2015
• Study Start: November 23, 2015
• Primary Completion: August 5, 2018
• Study Completion: August 5, 2018
• Last Updated: May 25, 2021
• Results First Posted: August 26, 2019

Record last verified: 2021-05

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

HU (3); CH (1); MY (5); PL (4); IL (1); RO (2); SG (3); DE (5); ES (4); UA (4); AU (2); US (14); GB (7); HK (2); SE (2); BU (3); IT (7); TW (3); TU (4); NO (1); FR (5)