Study of rFVIIIFc for Immune Tolerance Induction (ITI) in Haemophilia A Patients With Inhibitors Who Have Failed Previous ITI Therapies

NCT ID: NCT03103542

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-29
• Study Completion Date: 2020-08-31

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.

Conditions

Hemophilia A

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Recombinant coagulation factor VIII Fc (rFVIIIFc)

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.

Group Type: EXPERIMENTAL

Recombinant coagulation factor (rFVIIIFc)

Intervention Type: BIOLOGICAL

rFVIIIFc 200 IU/kg/day during ITI Period and thereafter adjusted according to the Investigator's judgement

administered intravenously.

Interventions

Recombinant coagulation factor (rFVIIIFc)

rFVIIIFc 200 IU/kg/day during ITI Period and thereafter adjusted according to the Investigator's judgement

administered intravenously.

Intervention Type: BIOLOGICAL

Other Intervention Names

ELOCTA; ELOCTATE

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

• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Bioverativ Therapeutics Inc.

INDUSTRY

Sponsor Role: collaborator

Swedish Orphan Biovitrum

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Physician

Role: STUDY_DIRECTOR

Study Medical Director

Locations

Swedish Orphan Biovitrum Research Site

Washington D.C., District of Columbia, United States

Swedish Orphan Biovitrum Research Site

Hamilton, , Canada

Swedish Orphan Biovitrum Research Site

Vancouver, , Canada

Swedish Orphan Biovitrum Research Site

Bonn, , Germany

Swedish Orphan Biovitrum Research Site

Frankfurt am Main, , Germany

Swedish Orphan Biovitrum Research Site

Mörfelden-Walldorf, , Germany

Swedish Orphan Biovitrum Research site

Dublin, , Ireland

Swedish Orphan Biovitrum Research Site

Ljubljana, , Slovenia

Swedish Orphan Biovitrum Research site

Gothenburg, , Sweden

Swedish Orphan Biovitrum Research Site

Birmingham, , United Kingdom

Swedish Orphan Biovitrum Research Site

Liverpool, , United Kingdom

Swedish Orphan Biovitrum Research Site

London, , United Kingdom

Countries

United States; Canada; Germany; Ireland; Slovenia; Sweden; United Kingdom

References

Konigs C, Meeks SL, Nolan B, Schmidt A, Lofqvist M, Dumont J, Leickt L, Nayak S, Lethagen S. Rescue immune tolerance induction with a recombinant factor Fc-fused VIII: prospective ReITIrate study of clinical, humoral and cellular immune responses. Ther Adv Hematol. 2024 Nov 23;15:20406207241300809. doi: 10.1177/20406207241300809. eCollection 2024.

Reference Type: DERIVED

PMID: 39583653 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-000065-73

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

Sobi.Elocta-003

Identifier Type: -

Identifier Source: org_study_id