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

September 17, 2024 updated by: Swedish Orphan Biovitrum

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
16

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
      • Hamilton, Canada
        • Swedish Orphan Biovitrum Research site
      • Vancouver, Canada
        • Swedish Orphan Biovitrum Research site
  • Germany
      • Bonn, Germany
        • Swedish Orphan Biovitrum Research site
      • Frankfurt am Main, Germany
        • Swedish Orphan Biovitrum Research site
      • Mörfelden-Walldorf, Germany
        • Swedish Orphan Biovitrum Research site
  • Ireland
      • Dublin, Ireland
        • Swedish Orphan Biovitrum Research site
  • Slovenia
      • Ljubljana, Slovenia, 1000
        • Swedish Orphan Biovitrum Research site
  • Sweden
      • Gothenburg, Sweden, 41345
        • Swedish Orphan Biovitrum Research site
  • United Kingdom
      • Birmingham, United Kingdom
        • Swedish Orphan Biovitrum Research site
      • Liverpool, United Kingdom
        • Swedish Orphan Biovitrum Research site
      • London, United Kingdom, WC1N 3JH
        • Swedish Orphan Biovitrum Research site
  • United States
    • District of Columbia
      • Washington, District of Columbia, United States, 20010-2970
        • Swedish Orphan Biovitrum Research site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 Names:
  • ELOCTATE
  • ELOCTA

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
up to 60 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Time to ITI Success
Time Frame: up to 60 weeks

Time to the patient reaches ITI success according to the pre-defined criteria

For the subset of patients who were classified as partial success at the end of the ITI period, the time to fulfillment of the criteria for partial success was also analyzed descriptively.
up to 60 weeks
Occurrence of Relapse During a 48-week Period Following Successful ITI Treatment
Time Frame: Up to 48 weeks
Relapse was defined as a positive inhibitor (≥0.6 BU/mL) on 2 consecutive assessments and incremental recovery ≤66 % of the expected incremental recovery on 2 consecutive assessments
Up to 48 weeks
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.
up to 60 weeks
Bleeding Rate During a 48-week Period Following Successful ITI Treatment
Time Frame: up to 48 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.
up to 48 weeks
Adverse Events (AEs)
Time Frame: SAEs - approx 166 weeks AEs - approx 110 weeks
All observed adverse events as a measure of tolerability. (AE=adverse event, SAE=serious adverse event, TEAE=treatment emergent adverse event)
SAEs - approx 166 weeks AEs - approx 110 weeks
Consumption of rFVIIIFc
Time Frame: Up to 60 weeks
Consumption will be assessed based on amount of administered study treatment during the ITI period.
Up to 60 weeks
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
up to 60 weeks
Number of Days Missed School or Work During a 48-week Period Following Successful ITI Treatment
Time Frame: up to 48 weeks
Days missed school or work will be registered by the patients in an electronic diary
up to 48 weeks
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
up to 60 weeks
Number of Hospitalizations During a 48-week Period Following Successful ITI Treatment
Time Frame: Up to 48 weeks
Days of hospitalization will be collected by the Investigator at the study visits
Up to 48 weeks
Adherence
Time Frame: up to 108 weeks
Defined as percentage of administered doses versus planned doses
up to 108 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Swedish Orphan Biovitrum

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Bioverativ Therapeutics Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Study Physician, Study Medical Director

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 29, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 4, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 31, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 31, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 31, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 6, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 19, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 17, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Sobi.Elocta-003
  • 2017-000065-73 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

According to Sobi's data sharing policy Sobi may share anonymized clinical study data with qualified researchers. Sobi commits to sharing clinical study data on participant level and summary data for medicines and indications approved by EMA and/or FDA. Data access will be granted in response to qualified research requests. All requests are evaluated by a cross functional panel of experts within Sobi.

IPD Sharing Time Frame

Evaluated on a case by case basis

IPD Sharing Access Criteria

A decision on data sharing will be based on the following:

  • The scientific merit of the proposal - i.e. the proposal should be scientifically sound, ethical, and have the potential to contribute to the advancement of public health.
  • The feasibility of the research proposal - i.e. the requesting research team must be scientifically qualified and have the resources to conduct the proposed project.
  • Maintenance of personal integrity - i.e. Sobi will not consider sharing individual data if there is a risk of re-identification of individuals despite a proper anonymisation. Moreover, the patients' informed consent will always be respected. Sobi reserves the right to reject the proposal if the anonymisation process will render unusable data.
  • Publication of results - the applicants should commit to submit their findings to a peer-reviewed scientific journal, alternatively to present the results at a congress (poster or similar), regardless of the research outcome

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Hemophilia A

Clinical Trials on Recombinant coagulation factor (rFVIIIFc)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings