A Longitudinal, Observational Study of Previously Treated Hemophilia Patients (PTPs) Switching Coagulation Replacement Factor Products (ATHN-2: Switching Study)

Study ID
STU 062015-091

Cancer Related
No

Healthy Volunteers
No

Study Sites

  • Children’s Medical Center (Dallas, Plano, Southlake)

Contact
Anna Winborn
2144568185
anna.winborn@childrens.com

Principal Investigator
Janna Journeycake, M.D.

Summary

This is a multi-center, longitudinal, observational, prospective study to assess inhibitor development within 1 year or 50 exposure days (eD), whichever is first, after switching factor replacement products in previously treated patients (PTPs) with hemophilia a or B.

The study will enroll approximately 600 patients with hemophilia who meet the eligibility criteria and are receiving care from one of the HTC centers into two (2) arms:
arm a (Prospective) will include patients who are switching factor replacement products and will be followed prospectively for up to 1 year.
arm B (Retrospective) will include patients who have switched factor replacement products previously (within the past 50 weeks at the time of enrollment). These patients will be assessed retrospectively and/or followed prospectively for up to 1 year.
Multiple cohorts will be studied; cohorts will be defined by the factor replacement preparations that become available during the study period. Research personnel and care providers will be educated about inclusion/exclusion criteria so that only appropriate patients are approached for informed consent.
Cohorts will be defined by the brand/type of new clotting factor replacement product approved after January 1, 2013. The current list of specific new products will be maintained in the Manual of operations. Currently these include eloctate[RegisteredTM] (Biogen-idec) and novoeight[RegisteredTM] (novonordisk) for Factor Viii; alprolix[RegisteredTM] (Biogen), Rixubis[RegisteredTM] (Baxter) and iXinity[RegisteredTM] (emergent Biosolutions) for Factor iX. others are imminent.

Primary outcome Measures
incidence of inhibitor to factor, by Bethesda assay and confirmed at a central laboratory, by 1 year (or 50 infusions, whichever comes first). asymptomatic inhibitor screening will be performed after 10 and 50 exposures, and unexpected bleeding or apparent treatment failure may prompt ad hoc clinical inhibitor screening. Subjects who reach the primary outcome will be censored for secondary study outcomes and followed separately.

Secondary outcome Measures
1. inhibitor incidence by factor product at asymptomatic screening after 10 exposures or 6 months, whichever is first.
2. inhibitor incidence in subjects with a prior history of inhibitors (but without detectable inhibitor at study entry).
3. efficacy outcome: Bleeding rates, by joint and by subject, stratified by factor product and by presence or absence of target joints at study entry.
4. incidence of safety events of special interest (i.e. the euHaSS-like events other than inhibitor).
5. Treatment emergent adverse events by factor type.
6. Reasons for switching factors at study entry (i.e. cycle 1), and if applicable, reasons for switching again after receiving at least one dose of cycle 1 product, after 1 year and/or at termination
7. Local Laboratory measures: HTC practice for inhibitor and factor assay methods (which may change) over time.
8. oPTionaL: Substudies for factor-specific module outcomes, as defined in the Manual of operations.

Participant Eligibility

1. Moderate or Severe Congenital Hemophilia A or B (FVIII or FIX clotting activity < 5% of normal).
2. Able to give informed consent (by patient or parent/authorized guardian).
3. Previously treated with plasma-derived or recombinant clotting factor replacement products with at least 50 exposure days (as assessed either from direct clinical records in children under age 5, or by clinical history of dosing in older patients). For Arm B being enrolled retrospectively, this previous treatment must be prior to switch under study.
4. Arm A: Planning to switch to a new brand or type of replacement factor VIII or FIX which was approved by the FDA after January 1, 2013 or
5. Arm B (Retrospective): Recently switched, within the previous 50 weeks to a new brand or type of replacement factor VIII or FIX which was approved by the FDA after January 1, 2013.
Note: History of prior transient inhibitor or inhibitor eradicated by immune tolerance induction (ITI) are eligible.