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)

NCT03093480 | Completed Phase 4 Results FDA Drug

• 3 other identifiers: LPS164732017-000373-36997HA402
• Study Type: interventional
• Target: 16
• Locations: 10 countries
• Sites: 37

Brief 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.

Conditions

Hemophilia A With Inhibitors

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• Number of Participants With Immune Tolerance Induction (ITI) Success

  Up to 48 Weeks

• Number of Participants Who Experienced Relapse

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

• Annualized Bleeding Rates During ITI Period

  Up to 48 weeks

• Annualized Bleeding Rates After ITI Period

  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

  Up to 2 Years

Study Arms (1)

Recombinant coagulation factor VIII Fc (rFVIIIFc)

EXPERIMENTAL

Participants were to 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 met the criteria for immune tolerance induction (ITI) success entered the tapering period and received 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 was for 32 weeks under an adjusted prophylactic regimen according to Investigator judgment.

Biological: rFVIIIFc

Interventions

rFVIIIFc BIOLOGICAL

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.

Also known as: ELOCTATE/ELOCTA; BIIB031; efmoroctocog alfa; antihemophilic factor [recombinant], Fc fusion protein

Recombinant coagulation factor VIII Fc (rFVIIIFc)

Eligibility Criteria

• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bioverativ, a Sanofi company: lead
• Swedish Orphan Biovitrum: collaborator

Study Sites (37)

Center for Inherited Blood Disorders

Orange, California, 92868, United States

Location

University of Colorado Hemophilia & Thrombosis Center

Aurora, Colorado, 80045, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Indiana Hemophilia and Thrombosis Center

Indianapolis, Indiana, 46260, United States

Location

University of Iowa Children's Hospital

Iowa City, Iowa, 52242, United States

Location

Childrens Hospital of Michigan

Detroit, Michigan, 48201, United States

Location

Dayton Children's Hospital

Dayton, Ohio, 45404, United States

Location

El Paso Children's Hospital

El Paso, Texas, 79905, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

Gulf States Hemophilia and Thrombophilia Center

Houston, Texas, 77030, United States

Location

Blood Center of Southeast Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

UMHAT "Sv. Georgi", EAD

Plovdiv, 4000, Bulgaria

Location

UMHAT 'Tsaritsa Yoanna - ISUL', EAD

Sofia, 1527, Bulgaria

Location

Children's & Women's Health Centre of British Columbia

Vancouver, British Columbia, V6H 3N1, Canada

Location

McMaster Children's Hospital

Hamilton, Ontario, L8N 3Z5, Canada

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Hôpital de la Timone

Marseille, Bouches-Du-Rhône, 13385, France

Location

CHU Besançon - Hôpital Jean Minjoz

Besançon, Doubs, 25030, France

Location

CHU de Toulouse - Hôpital Purpan

Toulouse, Haute Garonne, 31059, France

Location

Hemostase Clinique - Institut Cœur-Poumons (4eme étage aile est)

Lille, Nord, 59037, France

Location

Hôpital Necker - Enfants Malades

Paris, 75015, France

Location

Universitaetsklinikum Bonn AoeR

Bonn, North Rhine-Westphalia, 53127, Germany

Location

Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Azienda Ospedaliera Pediatrica Santobono Pausillipon

Napoli, 80122, Italy

Location

Ospedale San Bortolo di Vicenza

Vicenza, 36100, Italy

Location

Nagoya University Hospital

Nagoya, Aichi-ken, 466-8550, Japan

Location

St. Marianna University School of Medicine Hospital

Kawasaki, Kanagawa, 216-8511, Japan

Location

Nara Medical University Hospital

Kashihara-shi, Nara, 634-8521, Japan

Location

Hospital Universitari Vall d'Hebron

Barcelona, 8035, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

Location

St Thomas' Hospital

London, Greater London, SE1 7EH, United Kingdom

Location

John Radcliffe Hospital

Oxford, Oxfordshire, OX3 9DU, United Kingdom

Location

Royal Hospital for Children

Glasgow, Strathclyde, G514TF, United Kingdom

Location

Related Publications (1)

• Malec L, Van Damme A, Chan AKC, Spasova M, Jain N, Sensinger C, Dumont J, Lethagen S, Carcao M, Peyvandi F. Recombinant factor VIII Fc fusion protein for first-time immune tolerance induction: final results of the verITI-8 study. Blood. 2023 Apr 20;141(16):1982-1989. doi: 10.1182/blood.2022017780.

  PMID: 36735911 DERIVED

MeSH Terms

Interventions

factor VIII-Fc fusion protein; Factor VIII

Intervention Hierarchy (Ancestors)

Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Protein Precursors; Biological Factors

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Bioverativ, a Sanofi company

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2017
• First Posted: March 28, 2017
• Study Start: December 8, 2017
• Primary Completion: May 4, 2020
• Study Completion: February 16, 2021
• Last Updated: March 28, 2022
• Results First Posted: July 7, 2021

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

BE (2); BU (2); FR (5); US (12); GB (3); IT (3); CA (3); DE (1); JP (3); ES (3)