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

Phase 3

Completed

• Conditions: Congenital Bleeding Disorder; Haemophilia A
• Interventions: Drug: turoctocog alfa pegol

• Registration Number: NCT01731600
• Lead Sponsor: Novo Nordisk A/S

Brief Summary

This trial is conducted globally. The aim of the trial is to investigate safety, efficacy and pharmacokinetics (the exposure of the trial drug in the body) of NNC 0129-0000-1003 (N8-GP) in children with severe haemophilia A who have undergone treatment with previous factor VIII (FVIII) products.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-11-09
• Study First Submitted QC: 2012-11-16
• Study First Posted: 2012-11-22
• Study Start: 2013-02-20
• Primary Completion: 2014-09-15
• Disposition First Submitted: 2018-09-14
• Disposition First Submitted QC: 2018-09-14
• Disposition First Posted: 2018-09-18
• Study Completion: 2018-09-28
• Results First Submitted: 2019-09-19
• Results First Submitted QC: 2019-10-25
• Results First Posted: 2019-10-30
• Status Verified: 2020-11
• Last Update Submitted: 2020-11-03
• Last Update Posted: 2020-11-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 68

Inclusion Criteria

• Male patients with severe congenital haemophilia A (FVIII activity level below 1%)
• Weight above or equal to 10 kg - Documented history of 150 exposure days (ED) to FVIII products for patients aged 6-11 years and above 50 ED to FVIII products for patients aged 0-5 years

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Exclusion Criteria

• Any history of FVIII inhibitors

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
N8-GP	turoctocog alfa pegol	-

Primary Outcome Measures

Name	Time	Method
Number of Participants With Inhibitory Antibodies Against Coagulation Factor VIII (FVIII) ≥0.6 Bethesda Units	During the main phase of the trial (from 0-26 weeks of treatment)	The number of participants with inhibitory antibodies against coagulation factor VIII (FVIII) ≥0.6 Bethesda units was presented.

Secondary Outcome Measures

Name	Time	Method
Number of Bleeding Episodes During Prophylactic Treatment With N8-GP (Annualised Bleeding Rate)	Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)	The number of bleeding episodes per year reported during the prophylactic treatment with N8-GP.
Consumption of N8-GP Per Bleeding Episode (Number of Injections)	Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)	The mean number of injections of N8-GP used for treatment of a bleed from start to stop of a bleed.
Area Under the Curve Evaluated for N8-GP	From 1 hour prior to and up to 96 hours after initial administration of N8-GP	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.
Terminal Half-life Evaluated for N8-GP	From 1 hour prior to and up to 96 hours after initial administration of N8-GP	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.
Frequency of Adverse Events Including Serious Adverse Events Reported During the Trial Period	Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)	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.
Consumption of N8-GP During Prophylaxis (Number of Injections)	Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)	The mean number of injections of N8-GP used for treatment of a bleed from start to stop of a bleed during prophylaxis.
Incremental Recovery (Defined as the Peak Level Recorded 60 Min After End of Injection) Evaluated for N8-GP	From 1 hour prior to and up to 96 hours after initial administration of N8-GP	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.
Clearance Evaluated for N8-GP	From 1 hour prior to and up to 96 hours after initial administration of N8-GP.	Total plasma clearance of drug after intravenous administration measured as actual dose/AUC. A chromogenic assay with PSS as calibrator was used.
Haemostatic Effect of N8-GP When Used for Treatment of Bleeding Episodes and Assessed as: Excellent, Good, Moderate, or None	Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)	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.
Consumption of N8-GP Per Bleeding Episode (U/kg)	Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)	The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed.
Terminal Half-life Evaluated for Previous FVIII Product	2-6 weeks prior to initial dosing with N8-GP and up to 30 hours after administration of previous FVIII product	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.
Consumption of N8-GP During Prophylaxis (U/kg Per Month)	Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)	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 \[PK\])
Consumption of N8-GP During Prophylaxis (U/kg Per Year)	Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)	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)
Incremental Recovery (Defined as the Peak Level Recorded 60 Min After End of Injection) Evaluated for Previous FVIII Product	2-6 weeks prior to initial dosing with N8-GP and up to 30 hours after administration of previous FVIII product	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.
Area Under the Curve Evaluated for Previous FVIII Product	2-6 weeks prior to initial dosing with N8-GP and up to 30 hours after administration of previous FVIII product	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.
Clearance Evaluated for Previous FVIII Product	2-6 weeks prior to initial dosing with N8-GP and up to 30 hours after administration of previous FVIII product	Total plasma clearance of drug after intravenous administration measured as actual dose/AUC. A chromogenic assay with NHP as calibrator was used.

Trial Locations

Locations (1)

Novo Nordisk Investigational Site; 🇬🇧 Oxford, United Kingdom