Clinical trial NCT03103542: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hemophilia A
Keywords: ITI
rFVIIIFc
Immune Tolerance Induction
Lead sponsor: Swedish Orphan Biovitrum
Sponsor class: INDUSTRY
Collaborators: name: Bioverativ Therapeutics Inc.
First posted: 2017-04-06
Enrollment: 16
Sex: MALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: ITI Success
timeFrame: up to 60 weeks
Secondary outcomes:
measure: Time to ITI Success
timeFrame: up to 60 weeks
measure: Occurrence of Relapse During a 48-week Period Following Successful ITI Treatment
timeFrame: Up to 48 weeks
measure: Number of Bleedings During ITI Treatment
timeFrame: up to 60 weeks
measure: Bleeding Rate During a 48-week Period Following Successful ITI Treatment
timeFrame: up to 48 weeks
measure: Adverse Events (AEs)
timeFrame: SAEs - approx 166 weeks AEs - approx 110 weeks
measure: Consumption of rFVIIIFc
timeFrame: Up to 60 weeks
measure: Number of Days Missed School or Work During ITI Treatment
timeFrame: up to 60 weeks
measure: Number of Days Missed School or Work During a 48-week Period Following Successful ITI Treatment
timeFrame: up to 48 weeks
measure: Number of Hospitalizations During ITI Treatment
timeFrame: up to 60 weeks
measure: Number of Hospitalizations During a 48-week Period Following Successful ITI Treatment
timeFrame: Up to 48 weeks
measure: Adherence
timeFrame: up to 108 weeks
Other outcomes:
Locations:
city: Washington
country: United States
facility: Swedish Orphan Biovitrum Research Site
state: District of Columbia
city: Hamilton
country: Canada
facility: Swedish Orphan Biovitrum Research Site
city: Vancouver
country: Canada
facility: Swedish Orphan Biovitrum Research Site
city: Bonn
country: Germany
facility: Swedish Orphan Biovitrum Research Site
city: Frankfurt am Main
country: Germany
facility: Swedish Orphan Biovitrum Research Site
city: Mörfelden-Walldorf
country: Germany
facility: Swedish Orphan Biovitrum Research Site
city: Dublin
country: Ireland
facility: Swedish Orphan Biovitrum Research site
city: Ljubljana
country: Slovenia
facility: Swedish Orphan Biovitrum Research Site
city: Gothenburg
country: Sweden
facility: Swedish Orphan Biovitrum Research site
city: Birmingham
country: United Kingdom
facility: Swedish Orphan Biovitrum Research Site
city: Liverpool
country: United Kingdom
facility: Swedish Orphan Biovitrum Research Site
city: London
country: United Kingdom
facility: Swedish Orphan Biovitrum Research Site
Study officials:
affiliation: Study Medical Director
name: Study Physician
role: STUDY_DIRECTOR
References: