Early Prophylaxis Immunologic Challenge (EPIC) Study

NCT ID: NCT01376700

Last Updated: 2021-05-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-08-26
• Study Completion Date: 2012-11-16

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.

Conditions

Hemophilia A

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

ADVATE - Prophylactic Regimen

Weekly infusions of ADVATE. Study visits (physical examination, lab tests including FVIII inhibitor tests) every week during the first 10 exposure days (EDs), every 5 weeks during the next 10 EDs and every 10 weeks thereafter.

Group Type: EXPERIMENTAL

Recombinant antihemophilic factor, plasma/albumin-free method (rAHF-PFM)

Intervention Type: BIOLOGICAL

Intravenous infusion at a dose of 25 ± 5 IU/kg once per week. After 20 exposure days, the weekly infusions should be continued for as long as possible following the early prophylaxis period. If required by the clinical situation, dosing may be increased to twice weekly or even three times weekly after 20 exposure days, while keeping the low dose.

Interventions

Recombinant antihemophilic factor, plasma/albumin-free method (rAHF-PFM)

Intravenous infusion at a dose of 25 ± 5 IU/kg once per week. After 20 exposure days, the weekly infusions should be continued for as long as possible following the early prophylaxis period. If required by the clinical situation, dosing may be increased to twice weekly or even three times weekly after 20 exposure days, while keeping the low dose.

Intervention Type: BIOLOGICAL

Other Intervention Names

ADVATE

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

• Maximum Eligible Age: 1 Year
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Baxter Innovations GmbH

INDUSTRY

Sponsor Role: collaborator

Baxalta now part of Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Indianapolis, Indiana, United States

New Brunswick, New Jersey, United States

Vienna, , Austria

Sofia, , Bulgaria

Kingston, Ontario, Canada

Brno, , Czechia

Bonn, , Germany

Bremen, , Germany

Giessen, , Germany

Munich, , Germany

Vilnius, , Lithuania

Nijmegen, , Netherlands

Lublin, , Poland

Olsztyn, , Poland

Chelyabinsk, , Russia

Krasnodar, , Russia

Saint Petersburg, , Russia

Belgrade, , Serbia

A Coruña, , Spain

Countries

United States; Austria; Bulgaria; Canada; Czechia; Germany; Lithuania; Netherlands; Poland; Russia; Serbia; Spain

References

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.

Reference Type: RESULT

PMID: 25912619 (View on PubMed)

Other Identifiers

2011-000410-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

061002

Identifier Type: -

Identifier Source: org_study_id