Brief Title
Study of rFVIIIFc for Immune Tolerance Induction (ITI) in Haemophilia A Patients With Inhibitors Who Have Failed Previous ITI Therapies
Official Title
A Non-Controlled, Open-Label, Multicenter, Study of Immune Tolerance Induction Performed With rFVIIIFc Within a Timeframe of 60 Weeks in Severe Haemophilia A Patients With Inhibitors Who Have Failed Previous Immune Tolerance Induction Therapies
Brief Summary
The primary purpose of this study is to describe the outcome of Immune Tolerance Induction
(ITI) treatment performed with rFVIIIFc within a timeframe of 60 weeks in patients with
haemophilia A who have failed previous attempts at tolerization.
Detailed Description
This is an open-label, single-arm, interventional multi-center study designed to explore ITI
performed with recombinant coagulation factor VIII Fc fusion protein (rFVIIIFc) within a
timeframe of 60 weeks in patients with severe haemophilia A, who have failed previous
attempts at tolerization including use of immunosuppressants.
Study Phase
Phase 4
Study Type
Interventional
Primary Outcome
ITI success
Secondary Outcome
Time to ITI success
Condition
Hemophilia A
Intervention
Recombinant coagulation factor (rFVIIIFc)
Study Arms / Comparison Groups
Recombinant coagulation factor VIII Fc (rFVIIIFc)
Description: Participants will receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 60 Weeks during the ITI Period. Participants who meet the criteria for ITI success will enter a tapering period of 16 weeks where the dose will be tapered down until a prophylactic dose, as judged by the Investigator, is achieved and thereafter a follow-up period of 32 weeks where the patient will continue to receive prophylactic treatment with rFVIIIFc.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
16
Start Date
August 29, 2017
Completion Date
August 31, 2020
Primary Completion Date
September 4, 2019
Eligibility Criteria
Inclusion Criteria:
1. Signed and dated informed consent provided by the patient, or the patient's legally
authorized representative for patients under the legal age. Assent should be obtained
from pediatric patients according to local regulations
2. Male patients of any age diagnosed with severe haemophilia A, as confirmed from the
medical record
3. Previously treated with any plasma-derived or recombinant conventional or extended
half-life FVIII
4. Diagnosed with high titer inhibitors (historical peak ≥5 Bethesda units (BU)/mL
according to medical records)
5. Inhibitor titer >0.6 BU at screening
6. Failed previous ITI attempt(s) with any plasma-derived or recombinant conventional or
extended half-life FVIII including the use of immunosuppressant The attempt should be
documented in the medical records and have the following characteristics:
- A minimum FVIII dose equivalent to the low dose arm of the International ITI
study (50 IU/kg, 3 times/week)
- A minimum ITI treatment period of 33 months or
- Shorter than 33 months if no downward trend of at least 20% in the inhibitor
titer in a 6-month period after the initial 3 months of the ITI treatment
7. All patients must practice effective contraception during the study and for 3 months
after their last dose of study treatment
Exclusion Criteria:
1. Other coagulation disorder(s) in addition to haemophilia A
2. History of hypersensitivity reactions associated with any rFVIIIFc administration
3. High risk of cardiovascular, cerebrovascular, or other thromboembolic events, as
judged by the investigator
4. Planned major surgery to be deferred after study completion. Minor surgery such as
tooth extraction or insertion/replacement of central venous access device is allowed.
5. Concurrent systemic treatment with immunosuppressive drugs within 12 weeks 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 prior to Day 1) and/or inhaled steroids
6. Abnormal renal function (serum creatinine >2.0 mg/dL) as assessed by local lab
7. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5 × upper
limit of normal (ULN) as assessed by local lab
8. Serum total bilirubin >3 × ULN as assessed by local lab
9. Cluster of differentiation 4 (CD4) lymphocytes ≤200 mm3 if known as HIV antibody
positive at Screening
10. Viral load of ≥400 copies/mL if known HIV antibody positive at Screening
11. Patients with a documented history of alcohol or substance abuse within 12 months
prior to randomization
12. Previous inclusion in this study
13. Participation in another concurrent clinical interventional study within 30 days of
screening or intake of an investigational drug within five half-lives of that
investigational drug has passed
14. Foreseeable inability to cooperate with given instructions or study procedures
15. Presence of any medical or psychological condition or laboratory result that in the
opinion of the investigator can interfere with the patient's ability to comply with
the protocol requirements or makes the patient not appropriate for inclusion to the
study and treatment with rFVIIIFc
Gender
Male
Ages
N/A - N/A
Accepts Healthy Volunteers
No
Contacts
Stefan Lethagen, MD, PhD, ,
Location Countries
Belgium
Location Countries
Belgium
Administrative Informations
NCT ID
NCT03103542
Organization ID
Sobi.Elocta-003
Secondary IDs
2017-000065-73
Responsible Party
Sponsor
Study Sponsor
Swedish Orphan Biovitrum
Collaborators
Bioverativ Therapeutics Inc.
Study Sponsor
Stefan Lethagen, MD, PhD, Study Director, Study Medical Director
Verification Date
March 2021