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

This study is currently recruiting participants.
Verified October 2017 by Swedish Orphan Biovitrum
Sponsor:
ClinicalTrials.gov Identifier:
NCT03103542
First Posted: April 6, 2017
Last Update Posted: October 6, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Bioverativ Therapeutics Inc.
Information provided by (Responsible Party):
Swedish Orphan Biovitrum
  Purpose
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.

Condition Intervention Phase
Hemophilia A Biological: Recombinant coagulation factor (rFVIIIFc) Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Swedish Orphan Biovitrum:

Primary Outcome Measures:
  • ITI success [ Time Frame: up to 60 weeks ]

    Number of patients who achieve ITI success where ITI success is defined as achieving all 3 of the following criteria:

    • Negative titer for inhibitor (<0.6 Bethesda units/mL by the Nijmegen-modified Bethesda assay) at 2 consecutive visits
    • FVIII incremental recovery (IR) >66% of the expected IR at 2 consecutive visits
    • FVIII half-life (t½) ≥7 hours


Secondary Outcome Measures:
  • Time to ITI success [ Time Frame: up to 60 weeks ]
    Time to the patient reaches ITI success according to the pre-defined criteria

  • Occurrence of relapse during a 48-week period following successful ITI treatment [ Time Frame: Up to 108 weeks ]
    Relapse classified according to pre-defined criteria

  • Number of bleedings during ITI treatment [ Time Frame: up to 60 weeks ]
    Only bleeds requiring treatment with rFVIIIFc or bypassing agents should be registered. A bleeding episode starts from the first sign of a bleed and ends no more than 72 hours after the last injection of bypassing agents or rFVIIIFc to treat the bleeding episode.

  • Bleeding rate during a 48-week period following successful ITI treatment [ Time Frame: up to 108 weeks ]
    Only bleeds requiring treatment with rFVIIIFc or bypassing agents should be registered. A bleeding episode starts from the first sign of a bleed and ends no more than 72 hours after the last injection of bypassing agents or rFVIIIFc to treat the bleeding episode.

  • Adverse events (AEs) [ Time Frame: Up to 114 weeks ]
    AEs and Serious Adverse Events as a measure of tolerability

  • Consumption of rFVIIIFc [ Time Frame: Up to 108 weeks ]
    Consumption will be assessed based on amount of administered study treatment.

  • Number of days missed school or work during ITI treatment [ Time Frame: up to 60 weeks ]
    Days missed school or work will be registered by the patients in an electronic diary

  • Number of days missed school or work during a 48-week period following successful ITI treatment [ Time Frame: up to 108 weeks ]
    Days missed school or work will be registered by the patients in an electronic diary

  • Number of hospitalizations during ITI treatment [ Time Frame: up to 60 weeks ]
    Days of hospitalization will be collected by the Investigator at the study visits

  • Number of hospitalizations during a 48-week period following successful ITI treatment [ Time Frame: Up to 108 weeks ]
    Days of hospitalization will be collected by the Investigator at the study visits

  • Adherence [ Time Frame: up to 108 weeks ]
    Defined as percentage of administered doses versus planned doses


Estimated Enrollment: 20
Actual Study Start Date: August 29, 2017
Estimated Study Completion Date: April 1, 2020
Estimated Primary Completion Date: February 1, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Biological: Recombinant coagulation factor (rFVIIIFc)

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

administered intravenously.

Other Name: ELOCTA/ELOCTATE

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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03103542


Contacts
Contact: Emma Håkansson +4686972000 emma.hakansson@sobi.com
Contact: Karin Grünbaum +4686972000 karin.grunbaum@sobi.com

Locations
Belgium
Swedish Orphan Biovitrum Research site Recruiting
Brussels, Belgium, 1200
Germany
Swedish Orphan Biovitrum Research Site Recruiting
Bonn, Germany
Swedish Orphan Biovitrum Research Site Recruiting
Frankfurt am Main, Germany
Sponsors and Collaborators
Swedish Orphan Biovitrum
Bioverativ Therapeutics Inc.
Investigators
Study Director: Stefan Lethagen, MD, PhD Study Medical Director
  More Information

Responsible Party: Swedish Orphan Biovitrum
ClinicalTrials.gov Identifier: NCT03103542     History of Changes
Other Study ID Numbers: Sobi.Elocta-003
2017-000065-73 ( EudraCT Number )
First Submitted: March 31, 2017
First Posted: April 6, 2017
Last Update Posted: October 6, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Swedish Orphan Biovitrum:
ITI
rFVIIIFc
Immune Tolerance Induction

Additional relevant MeSH terms:
Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Factor VIII
Coagulants