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

Congenital Bleeding Disorder Clinical Trial

— pathfinder™5  

Official title:

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

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
• 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
• 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

Related Conditions & MeSH terms

• Blood Coagulation Disorders
• Congenital Bleeding Disorder
• Haemophilia A
• Hemophilia A
• Hemostatic Disorders

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.

External Links

•   Clinical Trials at Novo Nordisk