Research Trial to Study inhibitor development in previously untreated or minimally exposed Children to two different commercially available types of Factor VIII. This is Phase IV open lable , randomized,Study comparing Plasma derived Factor VIII with Recombinant Factor VIII.

Phase 4

Active, not recruiting

Brief Summary: The study is an international, multicenter, prospective, controlled, randomised, open-label clinical trial on inhibitor frequency in patients previously untreated (PUPs) or minimally blood component-treated (MBCTPs) when exposed to plasma-derived, von Willebrand factor-containing factor VIII (VWF/FVIII) concentrates or to recombinant factor VIII (rFVIII) concentrates. Patients meeting the enrolment criteria will be consecutively enrolled at each participating centre, randomised to be treated exclusively with a single FVIII product either plasma-derived and containing VWF or recombinant, and followed up until inhibitor development or until 50 exposure days (EDs) or 3 years from enrolment have elapsed, whichever comes first. Study products, belonging to the class of recombinant FVIII concentrates and to the class of VWF-containing FVIII concentrates, will be provided for free to the patients for all the duration of the study. A screening list will be held with consecutive patients that cannot be enrolled and with the reason of exclusion (refusal to enter the study, refusal of randomization, already exposed for 5 or more EDs to blood components or for less than 5 EDs to FVIII concentrates, FVIII levels ≥1).

Recruitment & Eligibility

Inclusion Criteria

Male subjects 2.
Any ethnicity 3.
Age 6 years 4.
Severe haemophilia A (FVIII:C 1%), as confirmed by the central laboratory 5.
A Patient with FVIII levels 1% and 2% will be separately recorded in the screening list 6.
Previously untreated (0 EDs to any FVIII concentrate or blood products) or minimally treated (5 EDs) with blood components, namely whole blood, fresh frozen plasma, packed red blood cells, platelets or cryoprecipitate 7.
A Patient not meeting these criteria will be separately recorded in the screening list.
Negative inhibitor measurement at both local and central laboratory at screening 9.
Ability to comply with study requirements 10.
Signed informed consent of legal tutors.

Exclusion Criteria

Plasma FVIII level â‰¥1%, as assayed at the central laboratory those patients originally diagnosed locally as severe but subsequently found to have FVIII levels ranging from 1% to 2% on testing at the central laboratory will be separately recorded in the screening list.
Previous history of FVIII inhibitor 3.
Other congenital or acquired bleeding defects 4.
Concomitant congenital or acquired immunodeficiencies 5.
Concomitant treatment with systemic immunosuppressive drugs 6.
Concomitant treatment with any investigational drug.

Primary Outcome Measures

Name	Time	Method
To assess the immunogenicity of VWF/FVIII and of rFVIII concentrates by determining the frequency of inhibitor development in PUPs and MBCTs in the first 50 EDs or in the first 3 years from enrolment, whichever comes first.	Enrollment visit,Every 3-4 EDs, Every 10 EDs,Every 3 months, Annual visit,Final visit

Secondary Outcome Measures

Name	Time	Method
To evaluate the frequency of transient inhibitors.	Enrollment visit,Every 3-4 EDs, Every 10 EDs, Every 3 months, Annual visit, final visit.
To evaluate the modality of occurrence of inhibitors (number of EDs, titre at onset, etc)	Enrollment visit,Every 3-4 EDs, Every 10 EDs, Every 3 months, Annual visit, final visit.
To evaluate the incidence of all other adverse events related and not related to the products used.	Enrollment visit,Every 3-4 EDs, Every 10 EDs, Every 3 months, Annual visit, final visit.
To evaluate the bleeding history (age at first bleed, bleeding pattern)	Enrollment visit,Every 3-4 EDs, Every 10 EDs, Every 3 months, Annual visit, final visit.
To evaluate the anamnestic response of inhibitor patients

Locations (10): All India Institute of Medical Sciences
🇮🇳
Delhi, DELHI, India
Centre for Blood Disorder
🇮🇳
Chennai, TAMIL NADU, India
Health and Research Centre
🇮🇳
Thiruvananthapuram, KERALA, India
Jehangir Clinical Development Centre
🇮🇳
Pune, MAHARASHTRA, India
Karnataka Hemophilia Society
🇮🇳
Davanagere, KARNATAKA, India
Kasturba Medical College
🇮🇳
Udupi, KARNATAKA, India
Lokmanya Tilak Municipal Medical college and general hospital
🇮🇳
Mumbai, MAHARASHTRA, India
Sahyadri Speciality Hospital
🇮🇳
Pune, MAHARASHTRA, India
Sir Ganga Ram Hospital
🇮🇳
Delhi, DELHI, India
St. Johns Medical College & Hospital
🇮🇳
Bangalore, KARNATAKA, India
All India Institute of Medical Sciences
🇮🇳Delhi, DELHI, India
Dr Tulika Seth
Principal investigator
91-9868397236
tuliseth@yahoo.com