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A Study to Evaluate Efficacy of rFVIIIFc for Immune Tolerance Induction (ITI) in Severe Hemophilia A Participants With Inhibitors Undergoing the First ITI Treatment (verITI-8 Study)

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ClinicalTrials.gov Identifier: NCT03093480
Recruitment Status : Active, not recruiting
First Posted : March 28, 2017
Last Update Posted : December 23, 2019
Sponsor:
Collaborator:
Swedish Orphan Biovitrum
Information provided by (Responsible Party):
Bioverativ Therapeutics Inc.

Tracking Information
First Submitted Date  ICMJE March 10, 2017
First Posted Date  ICMJE March 28, 2017
Last Update Posted Date December 23, 2019
Actual Study Start Date  ICMJE December 8, 2017
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 2, 2018)
Time to Tolerization With rFVIIIFc [ Time Frame: Up to 48 Weeks ]
Time required for participants to achieve ITI success where ITI success is defined as achieving all 3 of the following criteria: confirmed negative titers consisting of 2 consecutive negative inhibitor assessments within 2 weeks (less than [<] 0.6 Bethesda units/milliliter [mL] by the Nijmegen-modified Bethesda assay); incremental recovery (IR) greater than or equal to (>=) 66 percent (%) of the expected IR in 2 consecutive assessments; half-life (t½) >= 7 hours.
Original Primary Outcome Measures  ICMJE
 (submitted: March 22, 2017)
Time to Tolerization With rFVIIIFc [ Time Frame: Up to 12 Months ]
Tolerization is defined as inhibitor titer less than (<) 0.6 Bethesda units per milliliter (BU/mL).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 2, 2018)
  • Number of Participants With Immune Tolerance Induction (ITI) Success [ Time Frame: Up to 48 Weeks ]
    Number of participants who achieve ITI success where ITI success is defined as achieving all 3 of the following criteria: confirmed negative titers consisting of 2 consecutive negative inhibitor assessments within 2 weeks (<0.6 Bethesda units/mL by the Nijmegen-modified Bethesda assay); incremental recovery (IR) >= 66% of the expected IR at 2 consecutive assessments; half-life (t½) >=7 hours.
  • Number of Participants Who Experience Relapse [ Time Frame: Approximately 48 Weeks ]
    Number of Participants with ITI success who reaches the criteria for relapse (defined as confirmed positive inhibitor titer >= 0.6 BU/mL or abnormal recovery after tolerance is achieved, and t½ less than [<] 7 hours) will be evaluated during the Tapering or Follow-Up Periods.
  • Number of Bleeding Episodes During ITI, Tapering and Follow-Up periods [ Time Frame: Up to 2 Years ]
    A bleeding episode started from the first sign of a bleed and ended no more than 72 hours after the last treatment for the bleed, within which any symptoms of bleeding at the same location or injections less than or equal to 72 hours apart were considered the same bleeding episode.
  • Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability [ Time Frame: Up to 2 Years ]
    An AE is any untoward medical occurrence that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed in the definition.
  • Number of Days Away From Work or School [ Time Frame: Up to 2 Years ]
    Number of days missed from school or work will be summarized descriptively.
  • Number of Hospitalization Days [ Time Frame: Up to 2 Years ]
    Number of hospitalization days will be summarized descriptively.
  • Adherence to Treatment Regimen [ Time Frame: Up to 2 Years ]
    Defined as percentage of administered doses versus planned doses.
  • Consumption of rFVIIIFc [ Time Frame: Up to 2 Years ]
    Consumption will be assessed based on amount of administered study treatment.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 22, 2017)
  • Number of Participants With Immune Tolerance Induction (ITI) Success [ Time Frame: Up to 48 Weeks ]
    ITI Success will be defined as negative titer for inhibitor less than (<) 0.6 BU/mL by the Nijmegen-modified Bethesda assay.
  • Number of Participants Who Experience Relapse [ Time Frame: Up to 48 Weeks ]
    Number of Participants with ITI success who reaches the criteria for relapse (defined as inhibitor titer > 0.6 BU/mL or abnormal recovery after tolerance is achieved) will be evaluated.
  • Number of Bleeding Episodes During ITI and During the 48-week Period After Successful ITI performed with rFVIIIFc [ Time Frame: Up to Week 104 ]
    A bleeding episode started from the first sign of a bleed and ended no more than 72 hours after the last treatment for the bleed, within which any symptoms of bleeding at the same location or injections less than or equal to 72 hours apart were considered the same bleeding episode.
  • Number of Participants With Treatment-emergent Adverse Events (AEs) and Treatment-emergent Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability [ Time Frame: Approximately 2 Years ]
    An AE is any untoward medical occurrence that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed in the definition.
  • Number of Days Away From Work or School [ Time Frame: Up to Week 104 ]
    Number of days missed from school or work will be summarized descriptively.
  • Number of Hospitalization Days [ Time Frame: Up to Week 104 ]
    Number of hospitalization days will be summarized descriptively.
  • Adherence to Treatment Regimen [ Time Frame: Up to Week 104 ]
    Defined as percentage of administered doses versus planned doses.
  • Consumption of rFVIIIFc [ Time Frame: Up to Week 104 ]
    Consumption will be assessed based on amount of administered study treatment.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate Efficacy of rFVIIIFc for Immune Tolerance Induction (ITI) in Severe Hemophilia A Participants With Inhibitors Undergoing the First ITI Treatment (verITI-8 Study)
Official Title  ICMJE A Non-controlled, Open-Label, Multicenter, Study of Efficacy of rFVIIIFc for Immune Tolerance Induction (ITI) in Severe Hemophilia A Subjects With Inhibitors Undergoing the First ITI Treatment
Brief Summary The primary purpose of this study is to describe the time to tolerization (i.e., ITI success) with rFVIIIFc in participants within a maximum of 48 weeks (12 months) of ITI treatment.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hemophilia A With Inhibitors
Intervention  ICMJE Biological: rFVIIIFc
rFVIIIFc 200 IU/kg/day in ITI Period, 50 or 100 IU/kg (adjusted according to Investigator judgement) in tapering Period, and prophylactic regimen in Follow-Up period as powder for injection administered intravenously.
Other Name: ELOCTATE/ELOCTA
Study Arms  ICMJE 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 48 Weeks in ITI Period. Participants who meet the criteria for immune tolerance induction (ITI) success will enter the tapering period and will receive rFVIIIFc at a dose adjusted according to Investigator judgment based on the FVIII activity levels and with the aim of tapering the rFVIIIFc dose to reach a prophylactic dosing regimen within 16 weeks (4 months). Follow-Up will be 32 weeks under an adjusted prophylactic regimen according to Investigator judgment.
Intervention: Biological: rFVIIIFc
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: October 22, 2019)
16
Original Estimated Enrollment  ICMJE
 (submitted: March 22, 2017)
30
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Ability of the participant or his legally authorized representative (e.g., parent or legal guardian) to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information in accordance with national and local participant privacy regulations
  • Male participants of any age diagnosed with severe hemophilia A (as confirmed from the medical record)
  • Currently diagnosed with high titer inhibitors (historical peak greater than or equal to (>=) 5 Bethesda units per milliliter (BU/mL), according to medical records)
  • Previously treated with any plasma-derived or recombinant conventional or Extended Half-Life FVIII

Exclusion Criteria:

  • Other coagulation disorder(s) in addition to hemophilia A
  • Previous immune tolerance induction (ITI)
  • History of hypersensitivity or anaphylaxis associated with any factor VIII (FVIII) administration
  • Planned major surgery scheduled during the study unless deferred until after study completion (minor surgery such as tooth extraction or insertion/replacement of central venous access device is allowed)
  • Abnormal renal function (serum creatinine >1.5 milligram per deciliter (mg/dL) or 2 × upper limit of normal (ULN) for participant age based on local laboratory range) as assessed by local laboratory
  • Serum alanine aminotransferase or aspartate aminotransferase > 5 × upper limit of normal (ULN) as assessed by local laboratory
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Bulgaria,   Canada,   France,   Germany,   Italy,   Japan,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03093480
Other Study ID Numbers  ICMJE 997HA402
2017-000373-36 ( EudraCT Number )
997HA402 ( Other Identifier: Bioverativ Therapeutics Inc. )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bioverativ Therapeutics Inc.
Study Sponsor  ICMJE Bioverativ Therapeutics Inc.
Collaborators  ICMJE Swedish Orphan Biovitrum
Investigators  ICMJE Not Provided
PRS Account Bioverativ Therapeutics Inc.
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP