A Multinational, Open-Label, Non-Controlled Trial on Safety, Efficacy and Pharmacokinetics of NNC 0129-0000-1003 in Previously Treated Paediatric Patients With Severe Haemophilia A

The number of participants with inhibitory antibodies against coagulation factor VIII (FVIII) ≥0.6 Bethesda units was presented.

The frequency of adverse events including serious adverse events reported during the main and extension phase of the trial. The data presented is the rate of AE i.e. number of AEs per patient years of exposue.

Haemostatic effect of N8-GP for treatment of bleeding episodes was assessed by 4-point response scale: none, moderate, good or excellent. Evaluation during trial was done by patient and/or parent(s)/caregiver 8 hours after first injection as follows: Excellent: Abrupt pain relief and/or clear improvement in objective signs of bleeding within approximately 8 hours after a single injection; Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8 hours after a single injection, but possibly requiring more than one injection for complete resolution; Moderate: Probable or slight beneficial effect within approximately 8 hours after the first injection, but usually requiring more than one injection; None: No improvement, or worsening of symptoms.

The number of bleeding episodes per year reported during the prophylactic treatment with N8-GP.

The mean number of injections of N8-GP used for treatment of a bleed from start to stop of a bleed.

The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed.

The mean number of injections of N8-GP used for treatment of a bleed from start to stop of a bleed during prophylaxis.

The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed during prophylaxis (per month per subject). Consumption used for treatment includes all doses given (prophylaxis, treatment of bleed, minor surgery and pharmacokinetics [PK])

The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed during prophylaxis (per year per subject). Consumption used for treatment includes all doses given (prophylaxis, treatment of bleed, minor surgery and pharmacokinetics)

The incremental recovery was defined as the increase in plasma FVIII activity per IU/kg of factor administered recorded 60 minutes after end of injection. It was calculated as (Factor VIII procoagulant [FVIII:C] activity measured in plasma 60 min after dosing - FVIII:C activity measured in plasma immediately before dosing) / (dose injected at time 0 min), where the dose was expressed as U FVIII product per kg body weight. A chromogenic assay with normal human plasma (NHP) as calibrator was used.

The incremental recovery was defined as the peak level recorded 60 min after end of injection and dose-normalised. It was calculated as (FVIII:C activity measured in plasma 60 min after dosing - FVIII:C activity measured in plasma immediately before dosing) / (dose injected at time 0 min), where the dose was expressed as U FVIII product per kg body weight. A chromogenic assay with product specific calibrator (PSS) as calibrator was used.

Area under the curve (AUC) versus time from zero to infinity. This is calculated as AUC = AUClast + (C(t) / λz), where C(t) is the last measurable concentration. A chromogenic assay with NHP as calibrator was used.

Area under the curve versus time from zero to infinity. This is calculated as AUC = AUClast + (C(t) / λz), where C(t) is the last measurable concentration. A chromogenic assay with product specific standard (PSS) as calibrator was used.

t½ = ln(2) / λz, where t½ is terminal half-life and λz is the terminal elimination rate. The terminal elimination rate was planned estimated using linear regression on the terminal part of the time versus log(concentration) curve. A population-based method simultaneously estimating individual t½ values for all patients was applied, including patients with few values above the lower limit of quantification (LLOQ). This was estimated using time points from 1h to 30h. A chromogenic assay with PSS as calibrator was used.

t½ = ln(2) / λz, where λz is the terminal elimination rate. The terminal elimination rate was planned estimated using linear regression on the terminal part of the time versus log(concentration) curve. A population-based method simultaneously estimating individual t½ values for all patients was applied, including patients with few values above the LLOQ. This was estimated using time points from 6h to 96h. A chromogenic assay with PSS as calibrator was used.

Total plasma clearance of drug after intravenous administration measured as actual dose/AUC. A chromogenic assay with NHP as calibrator was used.

Total plasma clearance of drug after intravenous administration measured as actual dose/AUC. A chromogenic assay with PSS as calibrator was used.