Safety and Efficacy of Turoctocog Alfa in Previously Treated Male Children With Haemophilia A

• turoctocog alfa (Drug): Subjects will be treated 3 times per week or every second day with intravenous injections of turoctocog alfa. The dose range for preventive treatment is 25-60 IU/kg body weight depending on treatment regimen.
• turoctocog alfa (Drug): Subjects will undergo half-life evaluation of their current factor VIII product and pharmacokinetic session with turoctocog alfa before entering preventive treatment (subjects with available evaluation of terminal half-life within the last year are to be excluded from receiving factor VIII). Intravenous injections. The dose range for preventive treatment is 25-60 IU/kg body weight depending on treatment regimen.

Primary outcomes

• The Incidence Rate of FVIII Inhibitors (Greater Than or Equal to 0.6 Bethesda Units (BU)) [The adverse events were collected throughout the trial, corresponding to an average of 138 days per subject.]: The incidence rate of FVIII inhibitors was calculated by including all patients with inhibitors in the nominator and including all patients with a minimum 50 exposure plus any patients with less than 50 exposures but with inhibitors in denominator.

Secondary outcomes

• Frequency of Adverse Events (AEs) [The adverse events were collected throughout the trial, corresponding to an average of 138 days per subject]: Adverse event was defined as events occurring after administration of trial product. Severe AEs: considerable interference with subject's daily activities, unacceptable. Moderate AEs: Marked symptoms, moderate interference with the patient's daily activities. Mild AEs: No or transient symptoms, no interference with the patient's daily activities. Serious AE: AE that at any dose results in any of the following: death, a life-threatening experience, in-subject hospitalization/prolongation of existing hospitalisation, persistent/significant disability/incapacity/congenital anomaly/birth defect.

Sex: Male, ages: any to 11 Years

Inclusion Criteria:

* Male patients with severe (baseline FVIII less than or equal to 1%) haemophilia A
* Age below 12 years and weight at least 11 kg

Exclusion Criteria:

* Surgery planned to occur during trial participation (exceptions are port placement, dental extractions, and minor, uncomplicated emergent procedures)
* Congenital or acquired coagulation disorders other than haemophilia A
* Any history of FVIII inhibitors (greater than or equal to 0.6 BU/mL)

Participant flow

Outcome results

• The Incidence Rate of FVIII Inhibitors (Greater Than or Equal to 0.6 Bethesda Units (BU)) (Primary), Number, N with Inhibitors / N with ≥50 EDs: All Subjects Treated With Turoctocog Alfa 0
• Frequency of Adverse Events (AEs) (Secondary), Number, events: All Subjects Treated With Turoctocog Alfa 86

Adverse events

Time frame: The adverse events were collected throughout the trial, corresponding to an average of 138 days per subject.

Serious adverse events by term

Other adverse events by term

• Results publication: Kulkarni R, Karim FA, Glamocanin S, Janic D, Vdovin V, Ozelo M, Rageliene L, Carboni E, Laguna P, Dobaczewski G, Seremetis S, Lindblom A, Santagostino E. Results from a large multinational clinical trial (guardian3) using prophylactic treatment with turoctocog alfa in paediatric patients with severe haemophilia A: safety, efficacy and pharmacokinetics. Haemophilia. 2013 Sep;19(5):698-705. doi: 10.1111/hae.12165. Epub 2013 May 8. PMID 23651313
• Results publication: Santagostino E, Lentz SR, Misgav M, Brand B, Chowdary P, Savic A, Kilinc Y, Amit Y, Amendola A, Solimeno LP, Saugstrup T, Matytsina I. Safety and efficacy of turoctocog alfa (NovoEight(R)) during surgery in patients with haemophilia A: results from the multinational guardian clinical trials. Haemophilia. 2015 Jan;21(1):34-40. doi: 10.1111/hae.12518. Epub 2014 Oct 2. PMID 25273984
• Results publication: Ozelo MC. Updates from guardian: a comprehensive registration programme. Eur J Haematol. 2015 Dec;95 Suppl 81:22-9. doi: 10.1111/ejh.12648. PMID 26679394

• Global Clinical Registry (GCR, 1452), Study director, Novo Nordisk A/S

NIH grants: 2009