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)

Bioverativ, a Sanofi company16 enrolled

Overview

The primary purpose of this study was 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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hemophilia A With Inhibitors

Interventions

rFVIIIFcBIOLOGICAL

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.

Eligibility

Sex: MALE

Medical Language ↔ Plain English

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

Locations (37)

Outcomes

Primary Outcomes

Time to Tolerization With rFVIIIFc

Time required for participants to achieve immune tolerance induction (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.

Time frame: Up to 48 Weeks

Secondary Outcomes

Number of Participants With Immune Tolerance Induction (ITI) Success

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.

Time frame: Up to 48 Weeks

Number of Participants Who Experienced Relapse

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) evaluated during the Tapering or Follow-Up Periods

Time frame: Up to 48 weeks (16 weeks Tapering period and 32 weeks follow-up period)

Annualized Bleeding Rates During ITI Period

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. Annualized bleeding rate for a patient during the ITI period is defined as the number of bleeding episodes divided by the length of the ITI period in days\* 365.25.

Data from ClinicalTrials.gov

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Center for Inherited Blood Disorders

Orange, California, United States

University of Colorado Hemophilia & Thrombosis Center

Aurora, Colorado, United States

Children's National Medical Center

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

Rush University Medical Center

Chicago, Illinois, United States

Indiana Hemophilia and Thrombosis Center

Indianapolis, Indiana, United States

University of Iowa Children's Hospital

Iowa City, Iowa, United States

Childrens Hospital of Michigan

Detroit, Michigan, United States

Dayton Children's Hospital

Dayton, Ohio, United States

El Paso Children's Hospital

El Paso, Texas, United States

Cook Children's Medical Center

Fort Worth, Texas, United States

...and 27 more locations

Time frame: Up to 48 weeks

Annualized Bleeding Rates After ITI Period

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. Annualized bleeding rate for a patient after the ITT period (for tapering and follow-up period) is defined as the number of bleeding episodes divided by the length of the period after the ITI period in days\* 365.25.

Time frame: Up to 48 weeks (16 weeks Tapering period and 32 weeks follow-up period)

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs) as a Measure of Safety and Tolerability

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.

Time frame: Up to 2 Years

Average Number of Days Missed From Work or School Per Month During ITI Period

Average number of days missed from school or work per month for a period (counting in non-missing diary days) is defined as number of the missing school/work days in the period divided by number of days with data entry in the period. Number of days per month missed from school or work is reported for those who attend school or have a job.

Time frame: Up to 48 weeks

Average Number of Days Missed From Work or School Per Month After ITI Period

Time frame: Up to 48 weeks (16 weeks Tapering period & 32 weeks Follow-up period)

Annualized Number of Hospitalization Days During ITI Period

Annualized number of hospitalization days during a period for a patient is defined as the number of hospitalization days divided by the length of the period in days \* 365.25.

Time frame: Up to 48 weeks

Annualized Number of Hospitalization Days After ITI Period

Annualized number of hospitalization days during a period for a patient is defined as the number of hospitalization days divided by the length of the period in days \* 365.25.

Time frame: Up to 48 weeks (16 weeks Tapering period & 32 weeks Follow-up period)

Adherence to Treatment Regimen Overall Study Period

Adherence to treatment is based on prescribed daily dose for the overall study period which is defined as the percentage of administered doses versus the prescribed doses to a patient for the entire study duration.

Time frame: Up to 2 Years

Annualized rFVIIIFc Consumption for Overall Study Period

Annualized rFVIIIFc consumption for a treatment period is the total nominal rFVIIIFc (IU/kg) / length of period in days \* 365.25.

Time frame: Up to 2 Years