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)

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

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Hemophilia A With Inhibitors	Biological: rFVIIIFc	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: June 30, 2017
• Estimated Primary Completion Date: June 2021
• Estimated Study Completion Date: June 2021

Arms and Interventions

Arm

Intervention/treatment

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.

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

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. Number of Hospitalization Days [ Time Frame: Up to 2 Years ]
   Number of hospitalization days will be summarized descriptively.
7. Adherence to Treatment Regimen [ Time Frame: Up to 2 Years ]
   Defined as percentage of administered doses versus planned doses.
8. Consumption of rFVIIIFc [ Time Frame: Up to 2 Years ]
   Consumption will be assessed based on amount of administered study treatment.

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

  Show 37 Study Locations

Sponsors and Collaborators

Bioverativ Therapeutics Inc.

Swedish Orphan Biovitrum

More Information

• Responsible Party: Bioverativ Therapeutics Inc.
• ClinicalTrials.gov Identifier: NCT03093480 History of Changes
• Other Study ID Numbers: 997HA402; 2017-000373-36 ( EudraCT Number ); 997HA402 ( Other Identifier: Bioverativ Therapeutics Inc. )
• First Posted: March 28, 2017
• Last Update Posted: October 23, 2019
• Last Verified: October 2019

• 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

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