Clinical trial NCT01376700: Early Prophylaxis Immunologic Challenge (EPIC) Study
Official title: A Phase 3b Clinical Study to Assess Whether Regular Administration of ADVATE in the Absence of Immunological Danger Signals Reduces the Incidence Rate of Inhibitors in Previously Untreated Patients With Hemophilia A
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Hemophilia A
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Baxter Innovations GmbH
First posted: 2011-06-20
Enrollment: 22
Sex: MALE
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: The purpose of the study was to assess if a once-weekly prophylactic regimen of 25 IU/kg ADVATE started at or before 1 year of age and before the onset of a severe bleeding phenotype (ie, joint bleeding), together with the minimization of immunological danger signals, can reduce the incidence rate of inhibitor formation in PUPs with severe and moderately severe hemophilia A.


Eligibility criteria: Inclusion Criteria:

* Participants with severe and moderately severe hemophilia A (FVIII ≤ 2%)
* Participants \< 1 year of age
* Participants must have ≤ 3 exposure days (EDs) to any FVIII concentrate or FVIII-containing product used for treatment of minor bleeds (bleeds requiring no more than 2 infusions per event), or for preventative or precautionary infusions following possible injury
* Participants with prior circumcision are allowed to enroll only if bleeding issues related to circumcision were the cause for the original diagnosis of hemophilia A and no more than 2 EDs of FVIII treatment were required
* Adequate venous access (without need for central venous access device (CVAD)-placement) as determined by the physician
* Written informed consent from legally authorized representative(s)

Exclusion Criteria:

* Life-threatening conditions (intracranial hemorrhage, severe trauma) or requirement for surgery at the time of enrollment
* Evidence of inhibitor ≥ 0.6 Bethesda Unit (BU) in Nijmegen-modified Bethesda Assay at study start (samples may be retested using lupus-insensitive inhibitor tests to reduce the number of false positive inhibitor test results)
* Inherited or acquired hemostatic defect other than hemophilia A
* Any clinically significant, chronic disease other than hemophilia A
* Known hypersensitivity to ADVATE or any of its constituents
* Any planned elective surgery that cannot be postponed until after the first 20 EDs
* Participation in the Hemophilia Inhibitor Previously Untreated Patient Study
* Application of red blood cell, platelet, or leukocyte concentrates, or plasma
* Administration of any medication affecting coagulation or platelet function
* Systemic administration of any immunomodulatory drug (eg, chemotherapy, intravenous glucocorticoids)
* Participation in another clinical study involving an investigational product (IP) or device within 30 days prior to study enrollment or during the course of this study

Primary outcomes:
measure: Number of Participants With Severe and Moderately Severe Hemophilia A (FVIII ≤ 2%) With Factor VIII (FVIII) Inhibitor Formation Within the First 50 Exposure Days to ADVATE
timeFrame: 50 exposure days to ADVATE
Secondary outcomes:
measure: Number of Participants With Severe Hemophilia A (FVIII ≤ 1%) With Factor VIII (FVIII) Inhibitor Formation Within the First 50 Exposure Days to ADVATE
timeFrame: 50 exposure days to ADVATE
measure: Number of Exposure Days of Treatment With Advate Prior to First Positive Factor VIII (FVIII) Confirmed Inhibitor Assessment
timeFrame: 50 exposure days to ADVATE
measure: Number of Participants With Low-titer, High-titer, Transient, and All Factor VIII (FVIII) Inhibitors
timeFrame: 50 exposure days to ADVATE
measure: Number, Type, and Severity of All Bleeds Experienced When Different Prophylactic Dosing Frequencies Are Used (Once or Twice Per Week and Unknown Frequency)
timeFrame: 50 exposure days to ADVATE
measure: Number and Type of Surgeries
timeFrame: 50 exposure days to ADVATE
measure: Correlation of Known Risk Factors to Factor VIII (FVIII) Inhibitor Formation
timeFrame: 50 exposure days to ADVATE
measure: Total Factor VIII (FVIII) Consumption by Participant
timeFrame: 50 exposure days to ADVATE
measure: FVIII-Specific Antibody Isotype for All Participants at Study Entry and Every 10 Exposure Days (EDs)
timeFrame: 50 exposure days to ADVATE
measure: Number of Serious Adverse Events (SAEs) and Non-serious Adverse Events (Non-SAEs) at Least Possibly Related to ADVATE
timeFrame: 50 exposure days to ADVATE
Other outcomes:
Locations:
city: Indianapolis
country: United States
state: Indiana
city: New Brunswick
country: United States
state: New Jersey
city: Vienna
country: Austria
city: Sofia
country: Bulgaria
city: Kingston
country: Canada
state: Ontario
city: Brno
country: Czechia
city: Bonn
country: Germany
city: Bremen
country: Germany
city: Giessen
country: Germany
city: Munich
country: Germany
city: Vilnius
country: Lithuania
city: Nijmegen
country: Netherlands
city: Lublin
country: Poland
city: Olsztyn
country: Poland
city: Chelyabinsk
country: Russian Federation
city: Krasnodar
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Belgrade
country: Serbia
city: A Coruña
country: Spain
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Auerswald G, Kurnik K, Aledort LM, Chehadeh H, Loew-Baselli A, Steinitz K, Reininger AJ; EPIC clinical study group. The EPIC study: a lesson to learn. Haemophilia. 2015 Sep;21(5):622-8. doi: 10.1111/hae.12666. Epub 2015 Apr 23.