ADVATE 2 mL Post-Authorization Safety Surveillance (PASS)

ADVATE 2 mL (Reconstituted in 2 mL SWFI) POST-AUTHORIZATION SAFETY SURVEILLANCE STUDY

This is a Post-Authorization Safety Surveillance (PASS) study designed to collect data on the safety and effectiveness of ADVATE reconstituted in 2 mL Sterile water for injection (SWFI) during routine clinical practice in children until 12 years of age. This surveillance study is a post-licensure commitment for ADVATE reconstituted in 2 mL SWFI.

Study Overview

• Status: Completed
• Conditions: Hemophilia A; Congenital Factor VIII (FVIII) Deficiency
• Intervention / Treatment: Biological: Octocog alfa (recombinant human coagulation factor VIII) [ADVATE]

• Study Type: Observational
• Enrollment (Actual): 65

Contacts and Locations

Study Locations

• France
  • BORDEAUX Cedex, France, 33076
    • CHRU Pellegrin, Hématologie - CRTH
  • Chambery Cedex, France, 73011
    • Centre Hospitalier Générale, CTH
  • Dijon Cedex, France, 21034
    • CRTH Laboratoire d'Hématologie CHRU - Hôpital du Bocage
  • REIMS Cedex, France, 51092
    • American Memorial Hospital, Service de Pédiatrie
  • Rennes Cedex 09, France, 35033
    • CHU de Rennes Hopital Pontchaillou
  • Saint Priest En Jarez, France, 42270
    • Hôpital Nord, Pédiatrie
  • TOULOUSE Cedex 9, France, 31059
    • CHRU Purpan, CRTH - Pavillon Sénac
  • VANDOEUVRE-LES-NANCY Cedex, France, 54511
    • CHU de Nancy - Hôpital de Brabois- CRTH - Laboratoire Hémato-Hémostase
• Germany
  • Stuttgart, Germany, 70176
    • Klinikum Stuttgart, Olgahospital, Pädiatrie 5
  • Saarland
    • Homburg, Saarland, Germany, 66421
      • Universitätskliniken des Saarlandes, Klinik für pädiatrische Onkologie und Hämatologie
• Hungary
  • Budapest, Hungary, 1131
    • Heim Pál Children's Hospital, Department of Oncology
  • Miskolc, Hungary, 3629
    • Borsod-Abaúj-Zemplén County Hospital, Pediatric Dep
  • Mohacs, Hungary, 7700
    • Mohacsi Korhaz, Department of Pediatrics
  • Nyiregyhaza, Hungary, 4400
    • Josa Andras Egyetemi Oktatokorhaz, Department of Pediatrics
• United Kingdom
  • Birmingham, United Kingdom, B4 6NH
    • Birmingham Children's Hospital NHS Trust
  • London, United Kingdom, WC1N 3JH
    • Great Ormond Street Hospital for Children NHS Trust
  • West Yorkshire
    • Leeds, West Yorkshire, United Kingdom, LS1 3EX
      • Leeds General Infirmary

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 12 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study population will include 60 evaluable participants aged = 12 years with severe or moderately severe hemophilia A (Factor VIII (FVIII) = 2%) with documented prior exposure to FVIII concentrates.

Description

Inclusion Criteria:

• Severe or moderately severe hemophilia A (baseline Factor VIII (FVIII) ≤ 2%)
• ≤12 years of age
• Participant's legally authorized representative(s) has provided written informed consent
• Participant is prescribed ADVATE and will only receive ADVATE reconstituted in 2 mL sterile water for injection (SWFI)
• Documented history of prior exposure to ADVATE
• Documented evidence of negative inhibitor test result during ≤10 EDs prior to study entry

Exclusion Criteria:

• Known hypersensitivity to the active substance or to any of the excipients
• Known allergic reaction to mouse or hamster proteins
• Participant has a requirement for a major surgical procedure at the time of enrollment
• Participant has no prior exposure to a FVIII concentrate
• Participant currently being treated with an immune tolerance induction (ITI) regimen
• Participant has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia A (eg, qualitative platelet defect or von Willebrand disease)
• Participant has participated in another clinical study involving an investigational product (IP) or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device or PASS registry during the course of this study

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ADVATE - 2mL	Biological: Octocog alfa (recombinant human coagulation factor VIII) [ADVATE]; The investigators shall determine all treatment regimens according to product labeling information and standard practice.; Other Names: ADVATE; Antihemophilic Factor (Recombinant)- Plasma/albumin free method (rAHF-PFM)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of all local and general, hypersensitivity and infusion-related reactions, irrespective of product-related causality for the adverse events (AEs).	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and type of adverse events (or adverse experiences) (AEs) considered by the investigator to be causally related to ADVATE reconstituted in 2 mL sterile water for injection (SWFI)	Causally related = possibly or probably related	6 months
Number of Factor VIII (FVIII) inhibitors in all participants		6 months
Number of Factor VIII (FVIII) inhibitors in Previously Treated Patients (PTPs) (> 50 Exposure Days (EDs)) with baseline Factor VIII (FVIII) < 1% and no history of FVIII inhibitors prior to study entry		6 months
Number of Factor VIII (FVIII) inhibitors in Previously Treated Patients (PTPs) (> 50 Exposure Days (EDs)) with baseline Factor VIII (FVIII) ≤ 2% and no history of FVIII inhibitors prior to study entry		6 months
Subjective hemostatic effectiveness rating of excellent, good, fair, or none for each bleeding episode treated		6 months
Number of bleeding episodes treated with 1, 2, 3, ≥ 4 infusions of ADVATE reconstituted in 2 mL sterile water for injection (SWFI)		6 months
Total units of ADVATE reconstituted in 2 mL sterile water for injection (SWFI) administered to treat each bleeding episode		6 months
Overall effectiveness of prophylaxis in participants who are on a prophylactic regimen		6 months
Global assessment rating of hemostatic effectiveness of ADVATE reconstituted in 2 mL sterile water for injection (SWFI) in surgical or dental procedures	Global assessment rating = excellent, good, fair, or none	6 months
Change in Factor VIII (FVIII) treatment satisfaction and preference ratings from caregiver between ADVATE reconstituted in 5 mL and 2 mL sterile water for injection (SWFI)		6 months
Change in Factor VIII (FVIII) infusion volume and time to mix and infuse FVIII treatment between ADVATE reconstituted in 5 mL and 2 mL sterile water for injection (SWFI)		6 months

Collaborators and Investigators

• Sponsor: Baxalta now part of Shire

Publications and helpful links

Helpful Links

• To obtain more information on the study, click here/on this link.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 20, 2013
• Primary Completion (ACTUAL): January 20, 2016
• Study Completion (ACTUAL): January 20, 2016

Study Registration Dates

• First Submitted: March 19, 2014
• First Submitted That Met QC Criteria: March 19, 2014
• First Posted (ESTIMATE): March 21, 2014

Study Record Updates

• Last Update Posted (ACTUAL): March 17, 2021
• Last Update Submitted That Met QC Criteria: March 15, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A; Coagulants; Factor VIII
• Other Study ID Numbers: 061101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR