BAX 855 PK-guided Dosing

NCT ID: NCT02585960

Last Updated: 2021-05-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 135 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-23
• Study Completion Date: 2018-08-05

Brief Summary

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. To further characterize pharmacokinetic (PK) and pharmacodynamic (PD) parameters of BAX 855

Conditions

Hemophilia A

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Pharmacokinetic (PK) evaluation of BAX 855

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

Group Type: EXPERIMENTAL

PEGylated Recombinant Factor VIII

Intervention Type: BIOLOGICAL

Pharmacokinetic (PK) evaluation

FVIII trough target 1-3%

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

Group Type: EXPERIMENTAL

PEGylated Recombinant Factor VIII

Intervention Type: BIOLOGICAL

Standard treatment

FVIII trough target 8-12%

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

Group Type: EXPERIMENTAL

PEGylated Recombinant Factor VIII

Intervention Type: BIOLOGICAL

Intensified treatment

Interventions

PEGylated Recombinant Factor VIII

Pharmacokinetic (PK) evaluation

Intervention Type: BIOLOGICAL

PEGylated Recombinant Factor VIII

Standard treatment

Intervention Type: BIOLOGICAL

PEGylated Recombinant Factor VIII

Intensified treatment

Intervention Type: BIOLOGICAL

Other Intervention Names

BAX855; BAX 855; BAX 855; BAX855; BAX855; BAX 855

Eligibility Criteria

Inclusion Criteria

• Participants transitioning from another BAX 855 study who meet ALL of the following criteria are eligible for this study:

1. Participant has completed the end of study visit of a BAX 855 study or is transitioning from the ongoing Baxalta Continuation Study 261302.

2. 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.

3. Participant is human immunodeficiency virus negative (HIV-); or HIV+ with stable disease and CD4+ count ≥ 200 cells/mm^3, as confirmed by central laboratory.

4. 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:

1. 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

2. Participant has been previously treated with plasma-derived FVIII concentrates or recombinant FVIII for ≥ 150 documented exposure days (EDs)

3. 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.

4. Participant has a Karnofsky performance score of ≥ 60 at screening

5. Participant is HIV-; or HIV+ with stable disease and CD4+ count ≥ 200 cells/mm^3, as confirmed by central laboratory at screening

6. 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

7. 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

8. Participant is willing and able to comply with the requirements of the protocol.

Exclusion Criteria

• Participants transitioning from another BAX 855 study who meet ANY of the following criteria are not eligible for this study:

1. 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.

2. Participant has been diagnosed with an acquired hemostatic defect other than hemophilia A.

3. The participant's weight is < 35 kg or > 100 kg.

4. Participant's platelet count is < 100,000/mL.

5. Participant has an abnormal renal function (serum creatinine > 1.5 times the upper limit of normal).

6. Participant has active hepatic disease with alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels ≥ 5 times the upper limit of normal.

7. 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.

8. 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.

9. Participant is planning to take part in any other clinical study during the course of the study.

10. 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:

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 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.

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. The participant's weight is < 35 kg or > 100 kg.

5. Participant's platelet count is < 100,000/mL.

6. Participant has known hypersensitivity towards mouse or hamster proteins, PEG or Tween 80.

7. Participant has severe chronic hepatic dysfunction [eg, ≥ 5 times upper limit of normal alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST), as confirmed by central laboratory at screening, or a documented INR > 1.5].

8. Participant has severe renal impairment (serum creatinine > 1.5 times the upper limit of normal).

9. 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.

10. 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.

11. Participant has participated in another clinical study involving an 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.

12. 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.

13. 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.

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Baxalta Innovations GmbH, now part of Shire

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

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

Tucson, Arizona, United States

Children's Hospital Los Angeles

Los Angeles, California, United States

University of Colorado

Aurora, Colorado, United States

University of Florida College of Medicine

Gainesville, Florida, United States

Emory University-ECC

Atlanta, Georgia, United States

University of Kentucky Medical Center

Lexington, Kentucky, United States

University of Louisville KCPCRU

Louisville, Kentucky, United States

Tulane University

New Orleans, Louisiana, United States

Boston Children's Hospital

Boston, Massachusetts, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Gulf States Hemophilia Centre

Houston, Texas, United States

University of Utah

Salt Lake City, Utah, United States

University of Washington

Seattle, Washington, United States

Royal Brisbane Women's Hospital

Herston, Queensland, Australia

The Perth Blood Institute

Nedlands, Western Australia, Australia

AKH - Medizinische Universität Wien

Vienna, , Austria

UMHAT "Sv. Georgi", EAD

Plovdiv, , Bulgaria

UMHAT 'Tsaritsa Yoanna - ISUL', EAD

Sofia, , Bulgaria

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

Varna, , Bulgaria

CHU Nice- Service hematologie

Nice, Alpes Maritimes, France

Hôpital Morvan

Brest, Finistere, France

CHU Rennes - Hopital Pontchaillou

Rennes, Ille Et Vilaine, France

CHU de Caen - Hôpital Côte de Nacre

Caen, , France

CHU Charles Nicolle

Rouen, , France

HZRM Hamophilie Zentrum Rhein Main GmbH

Mörfelden-Walldorf, Hesse, Germany

Inst. f. Experimentelle Hamatologie u. Transfusionsmedizin

Bonn, North Rhine-Westphalia, Germany

COAGULATION RESEARCH CENTRE GmbH

Duisburg, North Rhine-Westphalia, Germany

Hamophiliezentrum/Gerinnungssprechstunde

Berlin, , Germany

MVZ Labor Dr. Reising-Ackermann

Leipzig, , Germany

University of Hong Kong

Hong Kong, , Hong Kong

Prince of Wales Hospital

Shatin, , Hong Kong

Magyar Honvedseg EK

Budapest, , Hungary

DE OEC Belgyógyászati Int

Debrecen, , Hungary

PTE ÁOK

Pécs, , Hungary

Chaim Sheba Medical Center

Tel Litwinsky, , Israel

UOC Ematologia, Azienda ULSS 8 Asolo, Regione Veneto

Castelfranco Veneto, Treviso, Italy

Presidio Osped. Ferrarotto

Catania, , Italy

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, , Italy

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

Roma, , Italy

Fondazione Policlinico Universitario A. Gemelli

Roma, , Italy

AOU Citta della Salute e della Scienza - Presidio Molinette

Torino, , Italy

ULSS n. 6 "Vicenza"

Vicenza, , Italy

Hospital Ampang

Ampang, Kuala Lumpur, Malaysia

Hospital Queen Elizabeth

Kota Kinabalu, Sabah, Malaysia

Hospital Kuala Lumpur

Kuala Lumpur, , Malaysia

Hospital Melaka

Malacca, , Malaysia

Hospital Pulau Pinang

Pulau Pinang, , Malaysia

Oslo Universitetssykehus HF

Oslo, , Norway

Wojewodzki Szpital Specjalistyczny im. Mikolaja Kopernika, Klinika Hematologii

Lodz, , Poland

Alvamed

Poznan, , Poland

Instytut Hematologii Ii Transfuzjologii

Warsaw, , Poland

SP Szpital Kliniczny Nr 1 we Wroclawiu

Wroclaw, , Poland

Spitalul Clinic Judetean de Urgenta Brasov

Brasov, , Romania

Institutul Oncologic ClNa.

Cluj-Napoca, , Romania

National University Hospital

Singapore, , Singapore

Singapore General Hospital- Parent

Singapore, , Singapore

KK Women's And Children's Hospital

Singapore, , Singapore

Hospital Universitari Son Espases

Palma de Mallorca, Balearic Islands, Spain

Complejo Hospitalario Universitario A Coruña

A Coruña, La Coruña, Spain

Hospital Regional Universitario de Malaga

Málaga, Málaga, Spain

Hospital Universitario La Paz

Madrid, , Spain

Sahlgrenska Universitetssjukhuset

Gothenburg, , Sweden

Karolinska Universitetssjukhuset

Stockholm, , Sweden

Universitätsspital Zürich

Zurich, , Switzerland

China Medical University Hospital

Taichung, , Taiwan

Taichung Veterans General Hospital

Taichung, , Taiwan

Tri-Service General Hospital

Taipei, , Taiwan

Acibadem Hastanesi

Adana, , Turkey (Türkiye)

Akdeniz University

Antalya, , Turkey (Türkiye)

Istanbul University

Istanbul, , Turkey (Türkiye)

Ege University

Izmir, , Turkey (Türkiye)

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

Kyiv, , Ukraine

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

Kyiv, , Ukraine

SI Institute of Blood Pathology and Transfusion Medicine of NAMSU

Lviv, , Ukraine

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

Poltava, , Ukraine

Bristol Royal Hospital for Children

Bristol, Avon, United Kingdom

Royal Free Hospital

London, Greater London, United Kingdom

Royal Manchester Children's Hospital

Manchester, Greater Manchester, United Kingdom

Southampton General Hospital

Southampton, Hampshire, United Kingdom

Leicester Royal Infirmary

Leicester, Leicestershire, United Kingdom

Churchill Hospital

Oxford, Oxfordshire, United Kingdom

University Hospital of Wales

Cardiff, West Glamorgan, United Kingdom

Countries

United States; Australia; Austria; Bulgaria; France; Germany; Hong Kong; Hungary; Israel; Italy; Malaysia; Norway; Poland; Romania; Singapore; Spain; Sweden; Switzerland; Taiwan; Turkey (Türkiye); Ukraine; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 37465396 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36655343 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33150384 (View on PubMed)

Provided Documents

Document Type: Study Protocol: Protocol

View Document

Document Type: Study Protocol: Amendment 1

View Document

Document Type: Study Protocol: Amendment 2

View Document

Document Type: Study Protocol: Amendment 3

View Document

Document Type: Study Protocol: Amendment 5

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2014-005477-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

261303

Identifier Type: -

Identifier Source: org_study_id