A clinical trial to study the safety and efficacy of PEGylated Factor VIII (BAX 855) in previously untreated patients (PUPs) 6 years with severe hemophilia A (FVIII 1%)
Phase 3
Active, not recruiting
- Conditions
- Other specified coagulation defects,
- Registration Number
- CTRI/2021/04/032837
- Lead Sponsor
- Baxalta Innovations GmbH
- Brief Summary
This study is a Phase 3, prospective, open-label, multicenter study to assess the safety, immunogenicity and hemostatic efficacy of BAX 855 in PUPs < 6 years of age with severe hemophilia A (baseline FVIII level < 1%) and < 3 EDs to ADVATE, BAX 855viii or plasma in at least 100 evaluable subjects. Subjects will receive prophylactic and/or on demand therapy with BAX 855 for at least 100 EDs or until they have developed a confirmed FVIII inhibitor (Part A). During Part A, subjects can undergo surgical or invasive procedures under a protocol-defined regimen for BAX 855. Subjects who develop a high titer FVIII inhibitor or subjects with low titer FVIII inhibitors where ITI therapy is necessary because of poorly controlled bleeding despite increased BAX 855 doses or bypassing agents are required to treat bleeding may enter Part B (ITI portion) of the study to undergo ITI therapy with BAX 855.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Closed to Recruitment of Participants
- Sex
- All
- Target Recruitment
- 12
Inclusion Criteria
- 1.Subject is < 6 years old at the time of screening 2.
- Subject is previously untreated with < 3 EDs to ADVATE, BAX 855 or Fresh Frozen Plasma (FFP) at any time prior to screening 3.
- Subject has severe hemophilia A (FVIII < 1%) as determined by the central laboratory, or a historical FVIII level < 1% as determined at any local laboratory, optionally supported by an additional FVIII gene mutation consistent with severe hemophilia A 4.
- Subject is immune competent with a CD4+ count > 200 cells/mm3, as confirmed by central laboratory at screening 5.
- Parent or legally authorized representative is willing and able to comply with the requirements of the protocol Additional inclusion criteria for Part B (ITI): 1 Parent or legal representative has/have voluntarily provided signed informed consent for ITI portion 2 Subject has a confirmed positive high titer inhibitor (> 5.00 BU) or has a positive confirmed low titer inhibitor (≥ 0.6 BU) as determined by the central laboratory based on a second repeat blood sample with a) poorly controlled bleeding despite increased BAX 855 doses, or b) requires bypassing agents to treat bleeding episodes.
Exclusion Criteria
- 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 S2.Subject has a 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 been previously treated with cryoprecipitate or any type of FVIII concentrate other than ADVATE, BAX 855v or FFP, or was administered ADVATE,BAX 855 or FFP for ≥ 3 Eds at any time prior to screening.
- 5 Subject has received any kind of blood-transfusion such as PRBC, platelets or plasma prior to screening at any time prior to screening 6 The subject’s weight is < 5 kg 7 Subject’s platelet count is < 100,000/mL 8 Subject has known hypersensitivity towards mouse or hamster proteins, PEG or Tween 80 9 Subject has severe chronic hepatic dysfunction [eg, > 5 times upper limit of normal alanine aminotransferase (ALT), aspartate aminotransferase (AST), or a documented INR > 1.5] in his medical history or at the time of screening 10 Subject has severe renal impairment (serum creatinine > 1.5 times the upper limit of normal) 11 Subject 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 1212.Subject 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 13 Subject 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 14 14.Parent or legally authorized representative has a medical, psychiatric, or cognitive illness or recreational drug/alcohol use that, in the opinion of the investigator, would affect subject safety or compliance 15 Parent, legally authorized representative or subject are 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.
- Additional exclusion criteria for Part B (ITI) 1 Spontaneous disappearance of the inhibitor prior to ITI 2 FVIII inhibitor titer ≥ 0.6 BU is not confirmed by a second new blood sample drawn within 2 weeks of study site notification of inhibitor and determined at the central laboratory 3 Inability or unwillingness to comply with the protocol.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Incidence of FVIII inhibitor development Success rate of Immune tolerance induction (ITI) Throughout Part A of the study, approximately 5 years | Up to 33 months
- Secondary Outcome Measures
Name Time Method •Assessment of intra-, post- and perioperative hemostatic efficacy in case of surgery •Intra- and postoperative blood loss in case of surgery •ABR during ITI •Weight-adjusted consumption of BAX 855 per month and per year for each ITI regimen employed Safety:•Binding IgG and IgM antibodies to FVIII, PEG-FVIII and PEG •AEs and SAEs Efficacy •Annualized bleeding rate (ABR) for prophylactic and on-demand treatment •Number of BAX 855 infusions per bleeding episode Additional Outcome Measures for ITI: Primary: The success rate of ITI therapy with BAX 855, success being defined as 1) a persistently negative inhibitor titer 0.6 BU (confirmed by central laboratory with second blood specimen obtained within 2 months); 2) a FVIII IR 66% of baseline value following a wash-out period of 84-96 h, and 3) a FVIII half-life of ≥ 6 hours.
Trial Locations
- Locations (7)
Amrita Institute of Medical Sciences and Research Centre
🇮🇳Ernakulam, KERALA, India
Christian Medical College
🇮🇳Vellore, TAMIL NADU, India
Institute of Medical Sciences and SUM Hospital
🇮🇳Sonapur, ORISSA, India
Nirmal Hospital Pvt Ltd
🇮🇳Surat, GUJARAT, India
NRS Medical College
🇮🇳Kolkata, WEST BENGAL, India
Sahyadri Super Specialty Hospital
🇮🇳Pune, MAHARASHTRA, India
St Johns Medical College Hospital
🇮🇳Bangalore, KARNATAKA, India
Amrita Institute of Medical Sciences and Research Centre🇮🇳Ernakulam, KERALA, IndiaDr Neeraj SidharthanPrincipal investigator9946047464neerajsidharthan@aims.amrita.edu