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

Study type

• Study topic:
  Human medicinal product

  Disease /health condition
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

  Effectiveness study (incl. comparative)

  Safety study (incl. comparative)
• Data collection methods:
  Primary data collection

Non-interventional study

• Non-interventional study design:
  Other
• Non-interventional study design, other:
  Observational post-authorization safety surveillance study (PASS) study

Study drug and medical condition

• Name of medicine:
  ADVATE
• Medical condition to be studied:
  Haemophilia A without inhibitors

Population studied

• Short description of the study population:
  Pediatric patients ≤ 12 years of age with severe or moderately severe hemophilia A.; ; Inclusion Criteria; Subjects who meet ALL of the following criteria are eligible for this study:;  Subject has severe or moderately severe hemophilia A (baseline FVIII ≤ 2%);  Subject is ≤12 years of age;  Subject’s legally authorized representative(s) has provided written informed consent;  Subject is prescribed ADVATE and will only receive ADVATE reconstituted in 2 mL SWFI;  Documented history of prior exposure to ADVATE (for subjects ≤ 2 years old, at least 3 EDs to ADVATE; for subjects with ≤ 50 EDs, all prior EDs must be to; ADVATE; for subjects with >50 EDs, the last 20 prior EDs must be to ADVATE);  Documented evidence of negative inhibitor test result during ≤10 EDs prior to study entry; ; Exclusion Criteria; Subjects who meet ANY of the following criteria are not eligible for this study:;  Subject has known hypersensitivity to the active substance or to any of the excipients;  Subject has a known allergic reaction to mouse or hamster proteins;  Subject has a requirement for a major surgical procedure at the time of enrollment;  Subject has no prior exposure to a FVIII concentrate;  Subject is currently being treated with an immune tolerance induction (ITI) regimen;  Subject has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia A (eg, qualitative platelet defect or von Willebrand disease);  Subject 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
• Age groups:
  Preterm newborn infants (0 – 27 days)

  Term newborn infants (0 – 27 days)

  Infants and toddlers (28 days – 23 months)

  Children (2 to < 12 years)

  Adolescents (12 to < 18 years)
• Estimated number of subjects:
  73

Study design details

• Main study objective:
  The primary objective of the study is to assess incidence of all local and general, hypersensitivity and infusion-related reactions, irrespective of product-related causality for the Adverse Events (AEs).
• Outcomes:
  The primary outcome measure is the incidence of all local and general, hypersensitivity and infusion-related reactions, irrespective of product related causality. Number: - and type of AEs causally related - inhibitors- all - inhibitors in Previously Treated Patients with >50 Exposure Days - bleeding episodes treated with 1, 2, 3, ≥4 infusions Hemostatic effectiveness rating Total units of ADVATE Overall prophylaxis effectiveness Change in FVIII between ADVATE 5mL and 2 mL: - treatment satisfaction and preference ratings - time to mix/infuse
• Data analysis plan:
  Statistical analysis will be descriptive in nature. Continuous variables will be described with means, standard deviations, minimum, first quartile, medians, interquartile ranges, third quartile, and maximum. Categorical variables will be expressed as frequencies and percentages. 95% confidence intervals of selected point estimates will be calculated. Paired statistical tests (parametric via t-test and/or non-parametric via Wilcoxon Signed- Rank test) will be employed to test for differences in infusion volume, time (to be captured in minutes and seconds) needed to mix and infuse FVIII, and satisfaction with ADVATE reconstituted in 5mL Sterile Water for Injection (SWFI) prior to enrolling in the study and ADVATE reconstituted in 2mL SWFI. Figures will be prepared to illustrate the patterns of data over time where appropriate.

Documents

Study results

061101-abstract-full-2016sep30_redacted_final_20170223