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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01731600
Other study ID # NN7088-3885
Secondary ID U1111-1129-60092
Status Completed
Phase Phase 3
First received
Last updated
Start date February 20, 2013
Est. completion date September 28, 2018

Study information

Verified date November 2020
Source Novo Nordisk A/S
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Completed
Enrollment 68
Est. completion date September 28, 2018
Est. primary completion date September 15, 2014
Accepts healthy volunteers No
Gender Male
Age group N/A to 11 Years
Eligibility 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 Exclusion Criteria: - Any history of FVIII inhibitors

Study Design


Intervention

Drug:
turoctocog alfa pegol
Fixed dose of turoctocog alfa pegol for intravenous injections (i.v.) twice weekly for prophylaxis. In addition, turoctocog alfa pegol will be administered to treat bleeding episodes during the trial period. Bleeding episodes will be treated with doses of 20-75 U/kg body weight.

Locations

Country Name City State
Brazil Novo Nordisk Investigational Site Rio de Janeiro
Canada Novo Nordisk Investigational Site Toronto Ontario
France Novo Nordisk Investigational Site Bron Cedex
France Novo Nordisk Investigational Site Lille
France Novo Nordisk Investigational Site Paris
Greece Novo Nordisk Investigational Site Athens
Greece Novo Nordisk Investigational Site Thessaloniki
Israel Novo Nordisk Investigational Site Tel-Hashomer
Italy Novo Nordisk Investigational Site Vicenza
Japan Novo Nordisk Investigational Site Kitakyusyu, Fukuoka
Japan Novo Nordisk Investigational Site Tokyo
Lithuania Novo Nordisk Investigational Site Vilnius
Malaysia Novo Nordisk Investigational Site Kuala Lumpur
Portugal Novo Nordisk Investigational Site Porto
Puerto Rico Novo Nordisk Investigational Site San Juan
Switzerland Novo Nordisk Investigational Site Bellinzona
Switzerland Novo Nordisk Investigational Site Luzern 16
Switzerland Novo Nordisk Investigational Site Zürich
Turkey Novo Nordisk Investigational Site Antalya
Turkey Novo Nordisk Investigational Site Bornova-IZMIR
Turkey Novo Nordisk Investigational Site Izmit
Turkey Novo Nordisk Investigational Site Samsun
Ukraine Novo Nordisk Investigational Site Donetsk
Ukraine Novo Nordisk Investigational Site Lviv
United Kingdom Novo Nordisk Investigational Site Leicester
United Kingdom Novo Nordisk Investigational Site London
United Kingdom Novo Nordisk Investigational Site Oxford
United States Novo Nordisk Investigational Site Boise Idaho
United States Novo Nordisk Investigational Site Boston Massachusetts
United States Novo Nordisk Investigational Site Charleston South Carolina
United States Novo Nordisk Investigational Site Charlotte North Carolina
United States Novo Nordisk Investigational Site Charlottesville Virginia
United States Novo Nordisk Investigational Site Cincinnati Ohio
United States Novo Nordisk Investigational Site Dallas Texas
United States Novo Nordisk Investigational Site Dayton Ohio
United States Novo Nordisk Investigational Site Houston Texas
United States Novo Nordisk Investigational Site Iowa City Iowa
United States Novo Nordisk Investigational Site Long Beach California
United States Novo Nordisk Investigational Site Minneapolis Minnesota
United States Novo Nordisk Investigational Site Nashville Tennessee
United States Novo Nordisk Investigational Site New Hyde Park New York
United States Novo Nordisk Investigational Site New Orleans Louisiana
United States Novo Nordisk Investigational Site Omaha Nebraska
United States Novo Nordisk Investigational Site Orange California
United States Novo Nordisk Investigational Site Orlando Florida
United States Novo Nordisk Investigational Site Philadelphia Pennsylvania
United States Novo Nordisk Investigational Site Philadelphia Pennsylvania
United States Novo Nordisk Investigational Site Phoenix Arizona
United States Novo Nordisk Investigational Site Spokane Washington
United States Novo Nordisk Investigational Site Tampa Florida
United States Novo Nordisk Investigational Site Washington District of Columbia

Sponsors (1)

Lead Sponsor Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Brazil,  Canada,  France,  Greece,  Israel,  Italy,  Japan,  Lithuania,  Malaysia,  Portugal,  Puerto Rico,  Switzerland,  Turkey,  Ukraine,  United Kingdom, 

References & Publications (2)

Šaulyte Trakymiene S, Economou M, Kenet G, Landorph A, Shen C, Kearney S. Long-term safety and efficacy of N8-GP in previously treated pediatric patients with hemophilia A: Final results from pathfinder5. J Thromb Haemost. 2020 Sep;18 Suppl 1:15-25. doi: — View Citation

Tosetto A, Neff A, Lentz SR, Santagostino E, Nemes L, Sathar J, Meijer K, Chowdary P, Shen C, Landorph A, Hampton K. Turoctocog alfa pegol provides effective management for major and minor surgical procedures in patients across all age groups with severe — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Number of Participants With Inhibitory Antibodies Against Coagulation Factor VIII (FVIII) =0.6 Bethesda Units The number of participants with inhibitory antibodies against coagulation factor VIII (FVIII) =0.6 Bethesda units was presented. During the main phase of the trial (from 0-26 weeks of treatment)
Secondary Frequency of Adverse Events Including Serious Adverse Events Reported During the Trial Period 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. 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)
Secondary Haemostatic Effect of N8-GP When Used for Treatment of Bleeding Episodes and Assessed as: Excellent, Good, Moderate, or None 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. 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)
Secondary Number of Bleeding Episodes During Prophylactic Treatment With N8-GP (Annualised Bleeding Rate) The number of bleeding episodes per year reported during the prophylactic treatment with N8-GP. 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)
Secondary Consumption of N8-GP Per Bleeding Episode (Number of Injections) The mean number of injections of N8-GP used for treatment of a bleed from start to stop of a bleed. 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)
Secondary Consumption of N8-GP Per Bleeding Episode (U/kg) The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed. 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)
Secondary Consumption of N8-GP During Prophylaxis (Number of Injections) The mean number of injections of N8-GP used for treatment of a bleed from start to stop of a bleed during prophylaxis. 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)
Secondary Consumption of N8-GP During Prophylaxis (U/kg Per Month) 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]) 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)
Secondary Consumption of N8-GP During Prophylaxis (U/kg Per Year) 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) 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)
Secondary Incremental Recovery (Defined as the Peak Level Recorded 60 Min After End of Injection) Evaluated for 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. 2-6 weeks prior to initial dosing with N8-GP and up to 30 hours after administration of previous FVIII product
Secondary Incremental Recovery (Defined as the Peak Level Recorded 60 Min After End of Injection) Evaluated for 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. From 1 hour prior to and up to 96 hours after initial administration of N8-GP
Secondary Area Under the Curve Evaluated for Previous FVIII Product Area under the curve (AUC) versus time from zero to infinity. This is calculated as AUC = AUClast + (C(t) / ?z), where C(t) is the last measurable concentration. A chromogenic assay with NHP as calibrator was used. 2-6 weeks prior to initial dosing with N8-GP and up to 30 hours after administration of previous FVIII product
Secondary Area Under the Curve Evaluated for N8-GP Area under the curve versus time from zero to infinity. This is calculated as AUC = AUClast + (C(t) / ?z), where C(t) is the last measurable concentration. A chromogenic assay with product specific standard (PSS) as calibrator was used. From 1 hour prior to and up to 96 hours after initial administration of N8-GP
Secondary Terminal Half-life Evaluated for Previous FVIII Product t½ = ln(2) / ?z, where t½ is terminal half-life and ?z 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. 2-6 weeks prior to initial dosing with N8-GP and up to 30 hours after administration of previous FVIII product
Secondary Terminal Half-life Evaluated for N8-GP t½ = ln(2) / ?z, where ?z 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. From 1 hour prior to and up to 96 hours after initial administration of N8-GP
Secondary Clearance Evaluated for 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. 2-6 weeks prior to initial dosing with N8-GP and up to 30 hours after administration of previous FVIII product
Secondary Clearance Evaluated for N8-GP Total plasma clearance of drug after intravenous administration measured as actual dose/AUC. A chromogenic assay with PSS as calibrator was used. From 1 hour prior to and up to 96 hours after initial administration of N8-GP.
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