Severe hemophilia A (FVIII <1%) MedDRA version: 19.0 Level: LLT Classification code 10060612 Term: Hemophilia A System Organ Class: 100000004850
Conditions
Interventions
Product Name: PEGylated rFVIII
Product Code: BAX 855 500IU/vial
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN:
Sponsors
Baxalta Innovations GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects transitioning from other BAX855 studies: Subjects transitioning from other BAX 855 studies who meet ALL of the following criteria are eligible for this study: 1. Subject has completed a previous BAX 855 study and is willing to immediately transition into this continuation study. 2. Subject is = 75 years of age at screening of the previous BAX 855 study. 3. Subject continues to have a Karnofsky (for subjects aged = 16 years) or Lansky (for subjects aged < 16 years) performance score of = 60 4. Subject is human immunodeficiency virus negative (HIV-); or HIV+ with stable disease and CD4+ count = 200 cells/mm3, as confirmed by central laboratory at screening. 5. Subject is hepatitis C virus negative (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. 6. If female of childbearing potential, subject presents with a negative urine pregnancy test and agrees to employ adequate birth control measures for the duration of the study. 7. Subject and/or legally authorized representative is willing and able to comply with the requirements of the protocol. BAX 855 naïve subjects BAX 855 naïve subjects 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 subjects who are < 12 years of age can only be enrolled in this continuation study after enrollment in the pediatric PTP study is closed. Enrolment of BAX 855 naïve subjects will only start once the sponsor has notified the study sites accordingly. BAX 855 naïve subjects who meet ALL of the following criteria are eligible for this study: 1. Subject is =75 years of age at screening. 2. Subject is naïve to BAX 855. 3. Subject has severe hemophilia A (FVIII clotting activity < 1%) as confirmed by central laboratory at screening after at least a 72-hour washout period. 4. Subject aged = 6 years has documented previous treatment with plasma-derived FVIII concentrates or rFVIII for = 150 EDs. 5. Subject aged < 6 years has documented previous treatment with plasma derived FVIII concentrates or rFVIII for = 50 EDs. 6. Subject is currently receiving prophylaxis or on-demand therapy with FVIII. 7. Subject has a Karnofsky (for subjects aged = 16 years) or Lansky (for subjects aged < 16 years) performance score of = 60 8. Subject is HIV-; or HIV+ with stable disease and CD4+ count = 200 cells/mm3, as confirmed by central laboratory at screening. 9. Subject 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, subject presents with a negative urine pregnancy test and agrees to employ adequate birth control measures for the duration of the study. 11. Subject and/or legally authorized representative is willing and able to comply with the requirements of the protocol. Are the trial subjects under 1
Exclusion criteria
Exclusion criteria: Subjects transitioning from other BAX855 studies: Subjects transitioning from other BAX 855 studies who meet ANY of the following criteria are not eligible for this study: 1. Subject had detectable FVIII inhibitory antibodies (= 0.6 BU using the Nijmegen modification of the Bethesda assay) as confirmed by central laboratory at screening. 2. Subject 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. Subject 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. Subject has severe chronic hepatic dysfunction (eg, = 5 times upper limit of normal alanine aminotransferase [ALT], as confirmed by central laboratory at screening). 5. Subject has severe renal impairment (serum creatinine > 2.0 mg/dL), as confirmed by central laboratory at screening. 6. Subject experienced a life-threatening or gastrointestinal bleeding episode within 3 months prior to study entry. 7. Subject is scheduled to use other PEGylated drugs during study participation. 8. Subject 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. Subject has medical, psychiatric, or cognitive illness or recreational drug/alcohol use that, in the opinion of the investigator, would affect subject safety or compliance. 10. Subject is a family member or employee of the investigator. BAX 855 naïve subjects BAX 855 naïve subjects who meet ANY of the following criteria are not eligible for this study: 1. Subject has detectable FVIII inhibitory antibodies (= 0.6 BU using the Nijmegen modification of the Bethesda assay) as confirmed by central laboratory at screening. 2. Subject 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. Subject has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia A (eg, qualitative platelet defect or von Willebrand’s disease). 4. Subject has known hypersensitivity towards mouse or hamster proteins, PEG, or Tween 80. 5. Subject has severe chronic hepatic dysfunction (eg, = 5 times upper limit of normal ALT, as confirmed by central laboratory at screening). 6. Subject has severe renal impairment (serum creatinine > 2.0 mg/dL), as confirmed by central laboratory at screening. 7. Subject experienced a life-threatening or gastrointestinal bleeding episode within 3 months prior to study entry. 8. Subject 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. Subject 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 IP or investigational device during the course of this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Safety: Development of inhibitory antibodies to FVIII Efficacy: Spontaneous ABR ; Main Objective: The co-primary objectives of the study are: 1. To determine the safety of BAX 855 based on the incidence of FVIII inhibitory antibody development 2. To determine the efficacy of BAX 855 based on the annualized bleed rate (ABR) of spontaneous bleeding episodes ; Secondary Objective: Efficacy 1. To determine the total ABR (spontaneous and traumatic bleeding episodes) 2. To determine the overall hemostatic efficacy rating of BAX 855 for treatment of breakthrough bleeding episodes 3. To determine the length of intervals between bleeding episodes 4. To characterize the hemostatic efficacy of BAX 855 for treatment of bleeding episodes by the number of BAX 855 infusions for treatment 5. To determine total weight-adjusted consumption of BAX 855 for prophylaxis and for treatment of bleeding episodes 6. To assess Patient Reported Outcomes (PROs) over time for subjects receiving BAX 855 Safety 1. To determine the safety of BAX 855, as assessed by the occurrence of adverse events (AEs) and changes in vital signs and clinical laboratory parameters 2. To determine the immunogenicity of BAX 855 ;Timepoint(s) of evaluation of this end point: All subjects will continue on study until a minimum of 100 EDs per subject have been achieved across all BAX 855 studies in which each subject participated. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy 1. Total ABR (spontaneous and traumatic bleeding episodes) 2. Overall hemostatic efficacy rating of BAX 855 for treatment of breakthrough bleeding episodes 3. Number of BAX 855 infusions to treat bleeding episodes 4. Time intervals between bleeding episodes 5. Weight-adjusted consumption of BAX 855 Safety 1. Occurrence of AEs and serious adverse events (SAEs) 2. Changes in vital signs and clinical laboratory parameters (hematology, clinical chemistry, and lipids) 3. Immunogenicity a. Binding antibodies (IgG and IgM) to FVIII, BAX 855, and PEG b. Anti-Chinese hamster ovary (CHO) antibodies Patient Reported Outcomes (PROs) Changes from baseline in parent study, if applicable, in the following: 1. Bleed and pain severity as measured using the Haemo-SYM questionnaire 2. Health-related quality of life (HRQoL) as assessed using the SF-36/PedsQL questionnaires ;Timepoint(s) of evaluation of this end point: All subjects will continue on study until a minimum of 100 EDs per subject have been achieved across all BAX 855 studies in which each subject participated. | — |
Countries
Australia, Austria, Belgium, Bulgaria, Czech Republic, Germany, Hong Kong, Israel, Japan, Korea, Republic of, Lithuania, Malaysia, Netherlands, Poland, Romania, Russian Federation, Spain, Sweden, Switzerland, Taiwan, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactArchana Savla
Baxalta Innovations GmbH
Outcome results
None listed