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

Phase 1

• Conditions: Severe Haemophilia A Patients with Inhibitors who have Failed Previous Immune Tolerance Induction Therapies; MedDRA version: 20.0Level: LLTClassification code 10018937Term: Haemophilia ASystem Organ Class: 100000004850; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2017-000065-73-IT
• Lead Sponsor: SWEDISH ORPHAN BIOVITRUM AB (PUBL)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Completion: 2020-08-31
• Study Start: 2021-05-25
• Last Update Posted: 7 June 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 16

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 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. Acceptable forms of birth control include barrier method (e.g. male condom, female condom, cervical cap, diaphragm, contraceptive sponge).
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 3
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1

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 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. 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

Exclusion criteria 9 and 10 refer to tests performed within 26 weeks prior to Screening. If results are not available, a new test should be drawn at the screening visit and analyzed locally prior to inclusion.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified