Clinical trial NCT01945593: BAX 855 Continuation
Official title: A Phase 3b Continuation Study of the Safety and Efficacy of PEGylated Recombinant Factor VIII (PEG-rFVIII; BAX 855) in Prophylaxis of Bleeding in Previously Treated Patients With Severe Hemophilia A
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hemophilia A
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Baxalta Innovations GmbH, now part of Shire
First posted: 2013-09-18
Enrollment: 218
Sex: ALL
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: To continue the evaluation of the safety and efficacy of BAX 855 for prophylaxis and treatment of bleeding episodes in adult and pediatric previously treated patients (PTPs) aged ≤ 75 years of age with severe hemophilia A.


Eligibility criteria: INCLUSION CRITERIA

Participants Transitioning from Other BAX 855 Studies:

Participants transitioning from other BAX 855 studies can be provided with the continuation study informed consent form (ICF) prior to the end of study visit to review and consider participation in this continuation study. These participants will complete any additional screening assessments within 2 weeks of the previous study's end of study visit and will return to the study site within 6 (± 1) weeks of the previous study end of study visit to confirm eligibility for this continuation study.

* Participants transitioning from other BAX 855 studies who meet ALL of the following criteria are eligible for this study:

  1. Participant has completed a previous BAX 855 study and is willing to immediately transition into this continuation study.
  2. Participant is ≤75 years of age at screening of the previous BAX 855 study.
  3. Participant continues to have a Karnofsky (for participants aged ≥ 16 years) or Lansky (for participants aged \< 16 years) performance score of ≥ 60.
  4. Participant is human immunodeficiency virus negative (HIV-); or HIV+ with stable disease and CD4+ count ≥ 200 cells/mm\^3, as confirmed by central laboratory at screening.
  5. Participant is hepatitis C virus negative (HCV-) by antibody or polymerase chain reaction (PCR) testing (if positive, antibody titer will be confirmed by PCR), as confirmed by central laboratory at screening; or HCV+ with chronic stable hepatitis.
  6. 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.
  7. Participant and/or legally authorized representative is willing and able to comply with the requirements of the protocol.
* BAX 855 Naïve Participants:

BAX 855 naïve participants who are ≥ 12 years of age can only be enrolled in this continuation study after enrollment in the phase 2/3 pivotal study is closed. BAX 855 naïve participants who are \< 12 years of age can only be enrolled in this continuation study after enrollment in the pediatric previously treated patient (PTP) study is closed.

- Enrolment of BAX 855 naïve participants will only start once the sponsor has notified the study sites accordingly.

BAX 855 naïve participants who meet ALL of the following criteria are eligible for this study:

1. Participant is ≤75 years of age at screening.
2. Participant is naïve to BAX 855.
3. Participant has severe hemophilia A (FVIII clotting activity \< 1%) as confirmed by central laboratory at screening after at least a 72-hour washout period.
4. Participant aged ≥ 6 years has documented previous treatment with plasma-derived FVIII or rFVIII for ≥ 150 exposure days (EDs).
5. Participant aged \< 6 years has documented previous treatment with plasma-derived FVIII concentrates or rFVIII for ≥ 50 EDs.
6. Participant is currently receiving prophylaxis or on-demand therapy with FVIII.
7. Participant has a Karnofsky (for participants aged ≥ 16 years) or Lansky (for participants aged \< 16 years) performance score of ≥ 60.
8. Participant is HIV-; or HIV+ with stable disease and CD4+ count ≥ 200 cells/mm\^3, as confirmed by central laboratory at screening.
9. Participant is HCV- by antibody or PCR testing (if positive, antibody titer will be confirmed by PCR), as confirmed by central laboratory at screening; or HCV+ with chronic stable hepatitis.
10. 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.
11. Participant and/or legally authorized representative is willing and able to comply with the requirements of the protocol.

EXCLUSION CRITERA

- Participants Transitioning from Other BAX 855 Studies:

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

1. Participant had detectable factor VIII (FVIII) inhibitory antibodies (≥ 0.6 Bethesda unit (BU) using the Nijmegen modification of the Bethesda assay) as confirmed by central laboratory at screening.
2. Participant has developed FVIII inhibitory antibodies (≥ 0.6 BU using the Nijmegen modification of the Bethesda assay as determined at central laboratory in a previous BAX 855 study).
3. Participant has acquired a hemostatic defect other than hemophilia A (eg, qualitative platelet defect or von Willebrand's disease) in a previous BAX 855 study.
4. Participant has severe chronic hepatic dysfunction (eg, ≥ 5 times upper limit of normal alanine aminotransferase \[ALT\], as confirmed by central laboratory at screening).
5. Participant has severe renal impairment (serum creatinine \> 2.0 mg/dL), as confirmed by central laboratory at screening.
6. Participant experienced a life-threatening or gastrointestinal bleeding episode within 3 months prior to study entry.
7. Participant is scheduled to use other PEGylated drugs during study participation.
8. Participant is planning to take part in any other clinical study during the course of the continuation study, with the exception of any other parallel BAX 855 study.
9. Participant has medical, psychiatric, or cognitive illness or recreational drug/alcohol use that, in the opinion of the investigator, would affect participant safety or compliance.
10. Participant is a family member or employee of the investigator.

    * BAX 855 Naïve Participants:

BAX 855 naïve participants 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 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 known hypersensitivity towards mouse or hamster proteins, polyethylene glycol (PEG), or Tween 80.
5. Participant has severe chronic hepatic dysfunction eg, ≥ 5 times upper limit of normal ALT, as confirmed by central laboratory at screening).
6. Participant has severe renal impairment (serum creatinine \> 2.0 mg/dL), as confirmed by central laboratory at screening.
7. Participant experienced a life-threatening or gastrointestinal bleeding episode within 3 months prior to study entry.
8. Participant has current or recent (\< 30 days) use of other PEGylated drugs prior to study participation or scheduled use of such drugs during study participation.
9. Participant has participated in another clinical study involving an IP other than BAX 855 or device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an investigational product (IP) or investigational device during the course of this study.
10. Participant has medical, psychiatric, or cognitive illness or recreational drug/alcohol use that, in the opinion of the investigator, would affect participant safety or compliance.
11. Participant is a family member or employee of the investigator.

Primary outcomes:
measure: Number of Participants With Inhibitory Antibodies to Factor VIII (FVIII)
timeFrame: Baseline through end of study (53 months)
measure: Annualized Bleed Rate (ABR) - Spontaneous Bleeds
timeFrame: Baseline through end of study (53 months)
Secondary outcomes:
measure: Total Annualized Bleed Rate (ABR)
timeFrame: Baseline through end of study (53 months)
measure: Overall Hemostatic Efficacy Rating of BAX 855 for Treatment of Breakthrough Bleeding Episodes
timeFrame: Baseline through end of study (53 months)
measure: BAX 855 Infusions Needed to Treat Bleeding Episodes
timeFrame: Baseline through end of study (53 months)
measure: Total Time Intervals Between Bleeding Episodes
timeFrame: Baseline through end of study (53 months)
measure: Average Dose of BAX 855 Per Prophylactic Infusion
timeFrame: Baseline through end of study (53 months)
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline through end of study (53 months)
measure: Change From Baseline in Body Temperature
timeFrame: Baseline, end of study (53 months)
measure: Change From Baseline in Pulse Rate
timeFrame: Baseline, end of study (53 months)
measure: Change From Baseline in Respiratory Rate
timeFrame: Baseline, end of study (53 months)
measure: Change From Baseline in Blood Pressure
timeFrame: Baseline, end of study (53 months)
measure: Number of Participants With Shifts in Clinical Chemistry Laboratory Assessments.
timeFrame: Baseline through end of study (53 months)
measure: Number of Participants With Shifts in Hematology Laboratory Assessments
timeFrame: Baseline through end of study (53 months)
measure: Number of Participants With Shifts in Lipid Panel Assessments
timeFrame: Baseline through end of study (53 months)
measure: Number of Participants With Binding Antibodies
timeFrame: Baseline through end of study (53 months)
measure: Number of Participants With Anti-Chinese Hamster Ovary (CHO) Antibodies
timeFrame: Baseline through end of study (53 months)
measure: Change From Baseline in Bleed Severity
timeFrame: Baseline, end of study (53 months)
measure: Change From Baseline in Pain Severity
timeFrame: Baseline, end of study (53 months)
measure: Change From Baseline in Patient Reported Outcomes: Health-related Quality of Life (HRQoL): Short Form-36 (SF-36)
timeFrame: Baseline, end of study (53 months)
measure: Change From Baseline in Patient Reported Outcomes: Health-related Quality of Life (HRQoL): Pediatrics Quality of Life (PedsQL) Questionnaire
timeFrame: Baseline, end of study (53 months)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Childrens Hospital
state: Arizona
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Gainesville
country: United States
facility: University of Florida College of Medicine
state: Florida
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Peoria
country: United States
facility: Bleeding and Clotting Disorders Institute
state: Illinois
city: Lexington
country: United States
facility: University of Kentucky Medical Center
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: New Orleans
country: United States
facility: Tulane University School of Medicine
state: Louisiana
city: Kansas City
country: United States
facility: Children's Mercy Hospitals & Clinics
state: Missouri
city: New Hyde Park
country: United States
facility: North Shore-Long Island Jewish Health System
state: New York
city: New York
country: United States
facility: New York - Presbyterian/Weill Cornell Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma
state: Oklahoma
city: Hershey
country: United States
facility: Penn State Hershey Cancer Center
state: Pennsylvania
city: Columbia
country: United States
facility: Palmetto Health Richland
state: South Carolina
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: Puget Sound Blood Group
state: Washington
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Fremantle
country: Australia
facility: Fremantle Hospital
state: Western Australia
city: Linz
country: Austria
facility: Landes-Frauen-und Kinderklinik Linz
city: Vienna
country: Austria
facility: Universitatsklinik fur Innere Medizin I
city: Plovdiv
country: Bulgaria
facility: UMHAT "Sv. Georgi", EAD
city: Sofia
country: Bulgaria
facility: SHAT of Oncohaematology Diseases
city: Varna
country: Bulgaria
facility: MHAT 'Sv. Marina', EAD
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc
city: Praha 5
country: Czechia
facility: Fakultni nemocnice v Motole
city: Hannover
country: Germany
facility: Werlhof-Institut GmbH
state: Niedersachsen
city: Duisburg
country: Germany
facility: Gerinnungszentrum Rhein-Ruhr
state: Nordrhein Westfalen
city: Berlin
country: Germany
facility: Vivantes Klinikum im Friedrichshain - Landsberger Allee
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf
city: Shatin
country: Hong Kong
facility: Prince of Wales Hospital
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Ramat-Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Nagoya-shi
country: Japan
facility: Nagoya University Hospital
state: Aichi-Ken
city: Kitakyushu-shi
country: Japan
facility: University of Occupational and Environmental Health Hospital
state: Fukuoka-Ken
city: Hiroshima-shi
country: Japan
facility: Hiroshima University Hospital
state: Hiroshima-Ken
city: Kawasaki-shi
country: Japan
facility: St. Marianna University School of Medicine Hospital
state: Kanagawa-Ken
city: Kashihara-shi
country: Japan
facility: Nara Medical University Hospital
state: Nara-Ken
city: Shinjuku-ku
country: Japan
facility: Tokyo Medical University Hospital
state: Tokyo-To
city: Suginami City
country: Japan
facility: Ogikubo Hospital
state: Tokyo
city: Hwasun-gun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
state: Jeollanam-do
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Daejeon
country: Korea, Republic of
facility: Eulji University Hospital
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Hospital at Gangdong
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santariskiu Clinics, Public Institution
city: Vilnius
country: Lithuania
facility: Children's Hospital, Affiliate of Vilnius University Hospital Santariskiu Klinikos
city: George Town
country: Malaysia
facility: Penang General Hospital
state: Penang
city: Kuching
country: Malaysia
facility: Hospital Umum Sarawak
state: Sarawak
city: Sibu
country: Malaysia
facility: Hospital Sibu
state: Sarawak
city: Ampang
country: Malaysia
facility: Hospital Ampang
state: Selangor
city: Kuala Lumpur
country: Malaysia
facility: Pusat Darah Negara
city: Pulau Pinang
country: Malaysia
facility: Hospital Pulau Pinang
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Lodz
country: Poland
facility: Wojewodzki Szpital Specjalistyczny im.M.Kopernika w Lodzi
city: Bucuresti
country: Romania
facility: Sanador SRL
city: Kirov
country: Russian Federation
facility: LLC "Alba Dent"
city: Krasnoyarsk
country: Russian Federation
facility: Regional Clinical Hospital
city: Palma de Mallorca
country: Spain
facility: Hospital Universitari Son Espases
state: Baleares
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña
state: La Coruña
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga
state: Málaga
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: Malmo
country: Sweden
facility: Sjukhusapoteket Malmo
city: Stockholm
country: Sweden
facility: Karolinska
city: Zuerich
country: Switzerland
facility: Universitaetsspital Zuerich
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
city: Ankara
country: Turkey
facility: Ankara University Medical Faculty
city: Antalya
country: Turkey
facility: Akdeniz University Faculty of Medicine
city: Istanbul
country: Turkey
facility: Istanbul University Cerrahpasa Medical Faculty
city: Donetsk
country: Ukraine
facility: SI V.K.Gusak Emergency and Reconstructive Surgery Institute of NAMSU
city: Lviv
country: Ukraine
facility: SI Institute of Blood Pathology and Transfusion Medicine of NAMSU
city: Bristol
country: United Kingdom
facility: Bristol Royal Hospital for Children
state: Avon
city: London
country: United Kingdom
facility: St Thomas' Hospital
state: Greater London
city: London
country: United Kingdom
facility: Royal Free Hospital
state: Greater London
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children
state: Greater London
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
state: Greater Manchester
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: Hampshire
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
state: Leicestershire
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
state: West Midlands
city: Oxford
country: United Kingdom
facility: The Churchill Hospital
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: