rFVIIIFc for Immune Tolerance Induction treatment

JRCT ID: jRCTs051180197

Registered date:26/03/2019

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Hemophilia A
• Date of first enrollment: 31/12/2018
• Target sample size: 30
• Countries of recruitment: USA,Japan,Europe,Japan,Canada,Japan
• Study type: Interventional

Intervention(s)

The ITI regimen consists of rFVIIIFc 200 IU/kg/day (plus/ minus 8 hours) will continue until all criteria for tolerization have been met or for a maximum of 48 weeks (12 months).
After all criteria for tolerization have been met, the rFVIIIFc dose administered will be adjusted according to Investigator judgment based on the FVIII activity levels to maintain the FVIII activity levels between 100 and 200 IU/dL during the initial part of the Tapering Period, with the aim of tapering the rFVIIIFc dose to reach a prophylactic dosing regimen within 16 weeks (4 months).

Outcome(s)

• Primary Outcome: To describe the time to tolerization (ITI success, i.e., inhibitor titer less than 0.6 BU/mL, rFVIIIFc incremental recovery [IR] over 66% of the expected IR, and t half over 7 hours) with rFVIIIFc in subjects within a maximum of 12 months (48 weeks) of ITI treatment.

Secondary Outcome

- To describe the outcome of ITI treatment
- To describe the relapse rate over the 48-week (12 month) period following successful ITI performed with rFVIIIFc
- To describe the intercurrent bleeding during the ITI Period and during the 48-week (12 month) period after successful ITI performed with rFVIIIFc
- To describe the safety and tolerability of rFVIIIFc when used for ITI
- To evaluate the impact of ITI treatment with rFVIIIFc on health economics and adherence

Key inclusion & exclusion criteria

• Age minimum: Not applicable
• Age maximum: Not applicable
• Gender: Male

Include criteria

1. Ability of the subject or his legally authorized representative (e.g., parent or legal guardian) to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information in accordance with national and local subject privacy regulations
2. Male subjects of any age diagnosed with severe hemophilia A (as confirmed from the medical record)
3. Currently diagnosed with high-titer inhibitors (historical peak over 5 BU/mL, according to medical records)
4.Previously treated with any pd-FVIII or recombinant conventional or Extended Half-Life FVIII

Exclude criteria

1. Other coagulation disorder(s) in addition to hemophilia A
2. Previous ITI
3. History of hypersensitivity or anaphylaxis associated with any FVIII administration
4. Planned major surgery scheduled during the study unless deferred until after study completion (minor surgery such as tooth extraction or insertion/replacement of central venous access device is allowed)
5. Abnormal renal function (serum creatinine over 1.5 mg/dL or 2 by upper limit of normal (ULN) for subject age based on local laboratory range) as assessed by local laboratory
6. Serum alanine aminotransferase or aspartate aminotransferase over 5 by ULN as assessed by local laboratory
7. Serum total bilirubin over 3 by ULN as assessed by local laboratory
8. Current enrollment or a plan to enroll in any interventional clinical study in which an investigational treatment or approved therapy, other than r FVIII Fc, for investigational use is administered within 30 days (or 5 half lives of the agent, whichever is longer) prior to the Baseline Visit
9. Inability to comply with study requirements
10. Presence of any medical or psychological condition or laboratory result that, in the opinion of the Investigator, can interfere with the subject's ability to comply with the protocol requirements or make the subject not appropriate for inclusion to the study and treatment with Elocta/Eloctate (rFVIIIFc)
11. Other unspecified reasons that, in the opinion of the Investigator or Sponsor, make the subject unsuitable for enrollment
12. Unwillingness or inability to comply with the requirements of the protocol, including the presence of any condition (physical, mental, or social) that prevents the subject from participating in visits as scheduled or entering required information into the EPD in a timely manner
13. Concurrent systemic treatment with immunosuppressive drugs within 12 weeks (3 months) prior to Screening. Exceptions to this include ribavirin for treatment of hepatitis C virus (HCV), and/or systemic steroids (a total of 2 courses of pulse treatments lasting no more than 7 days within 12 weeks [3 months] prior to Day 1) and/or inhaled steroids
14. High risk of cardiovascular, cerebrovascular, or other thromboembolic events, as judged by the Investigator
The following criteria refer to tests performed within 26 weeks (6.5 months) prior to Screening. If not available, a new test will be drawn at the Screening Visit.
15. Cluster of differentiation 4 (CD4) lymphocytes less than 200 mm3 at Screening, if known as human immunodeficiency virus (HIV) antibody positive based on medical history or HIV testing
16. Viral load of over 400 copies/mL at Screening, if known as HIV antibody positive based on medical history

Related Information

• Primary Sponsor: Nogami Keiji
• Secondary Sponsor: Bioverativ Therapeutics Inc,Bioverativ Therapeutics Inc
• Secondary ID(s): JapicCTI-183878