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)

Hemophilia A With Inhibitors Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03093480
• Other study ID #: LPS16473
• Secondary ID: 2017-000373-3699
• Status: Completed
• Phase: Phase 4
• Start date: December 8, 2017
• Est. completion date: February 16, 2021

Study information

• Verified date: March 2022
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: February 16, 2021
• Est. primary completion date: May 4, 2020
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Hemophilia A
• Hemophilia A With Inhibitors

Intervention

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.

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint-Luc	Bruxelles
Belgium	UZ Leuven	Leuven
Bulgaria	UMHAT "Sv. Georgi", EAD	Plovdiv
Bulgaria	UMHAT 'Tsaritsa Yoanna - ISUL', EAD	Sofia
Canada	McMaster Children's Hospital	Hamilton	Ontario
Canada	The Hospital for Sick Children	Toronto	Ontario
Canada	Children's & Women's Health Centre of British Columbia	Vancouver	British Columbia
France	CHU Besançon - Hôpital Jean Minjoz	Besançon	Doubs
France	Hemostase Clinique - Institut Cœur-Poumons (4eme étage aile est)	Lille	Nord
France	Hôpital de la Timone	Marseille	Bouches-Du-Rhône
France	Hôpital Necker - Enfants Malades	Paris
France	CHU de Toulouse - Hôpital Purpan	Toulouse	Haute Garonne
Germany	Universitaetsklinikum Bonn AoeR	Bonn	North Rhine-Westphalia
Italy	Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico	Milano
Italy	Azienda Ospedaliera Pediatrica Santobono Pausillipon	Napoli
Italy	Ospedale San Bortolo di Vicenza	Vicenza
Japan	Nara Medical University Hospital	Kashihara-Shi	Nara-Ken
Japan	St. Marianna University School of Medicine Hospital	Kawasaki	Kanagawa-Ken
Japan	Nagoya University Hospital	Nagoya-shi	Aichi-Ken
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitari i Politecnic La Fe	Valencia
United Kingdom	Royal Hospital for Children	Glasgow	Strathclyde
United Kingdom	St Thomas' Hospital	London	Greater London
United Kingdom	John Radcliffe Hospital	Oxford	Oxfordshire
United States	University of Colorado Hemophilia & Thrombosis Center	Aurora	Colorado
United States	Rush University Medical Center	Chicago	Illinois
United States	Dayton Children's Hospital	Dayton	Ohio
United States	Childrens Hospital of Michigan	Detroit	Michigan
United States	El Paso Children's Hospital	El Paso	Texas
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	Gulf States Hemophilia and Thrombophilia Center	Houston	Texas
United States	Indiana Hemophilia and Thrombosis Center	Indianapolis	Indiana
United States	University of Iowa Children's Hospital	Iowa City	Iowa
United States	Blood Center of Southeast Wisconsin	Milwaukee	Wisconsin
United States	Center for Inherited Blood Disorders	Orange	California
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Bioverativ, a Sanofi company	Swedish Orphan Biovitrum

Countries where clinical trial is conducted

United States,  Belgium,  Bulgaria,  Canada,  France,  Germany,  Italy,  Japan,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 48 Weeks
Secondary	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.	Up to 48 Weeks
Secondary	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	Up to 48 weeks (16 weeks Tapering period and 32 weeks follow-up period)
Secondary	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.	Up to 48 weeks
Secondary	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.	Up to 48 weeks (16 weeks Tapering period and 32 weeks follow-up period)
Secondary	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.	Up to 2 Years
Secondary	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.	Up to 48 weeks
Secondary	Average Number of Days Missed From Work or School Per Month After 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.	Up to 48 weeks (16 weeks Tapering period & 32 weeks Follow-up period)
Secondary	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.	Up to 48 weeks
Secondary	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.	Up to 48 weeks (16 weeks Tapering period & 32 weeks Follow-up period)
Secondary	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.	Up to 2 Years
Secondary	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.	Up to 2 Years