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 (pathfinder™5)

November 3, 2020 updated by: Novo Nordisk A/S
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.

Study Overview

Status

Completed

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

68

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Rio de Janeiro, Brazil, 20211-030
        • Novo Nordisk INvestigational Site
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • Novo Nordisk INvestigational Site
      • Bron Cedex, France, 69677
        • Novo Nordisk INvestigational Site
      • Lille, France, 59097
        • Novo Nordisk INvestigational Site
      • Paris, France, 75015
        • Novo Nordisk INvestigational Site
      • Athens, Greece, GR-11527
        • Novo Nordisk INvestigational Site
      • Thessaloniki, Greece, GR 54642
        • Novo Nordisk INvestigational Site
      • Tel-Hashomer, Israel, 52621
        • Novo Nordisk INvestigational Site
      • Vicenza, Italy, 36100
        • Novo Nordisk INvestigational Site
      • Kitakyusyu, Fukuoka, Japan, 807 8555
        • Novo Nordisk INvestigational Site
      • Tokyo, Japan, 167-0035
        • Novo Nordisk INvestigational Site
      • Vilnius, Lithuania, LT-08406
        • Novo Nordisk INvestigational Site
      • Kuala Lumpur, Malaysia, 50400
        • Novo Nordisk INvestigational Site
      • Porto, Portugal, 4200-319
        • Novo Nordisk INvestigational Site
      • San Juan, Puerto Rico, 00935
        • Novo Nordisk INvestigational Site
      • Bellinzona, Switzerland, 6500
        • Novo Nordisk INvestigational Site
      • Luzern 16, Switzerland, 6000
        • Novo Nordisk INvestigational Site
      • Zürich, Switzerland, 8032
        • Novo Nordisk INvestigational Site
      • Antalya, Turkey, 01010
        • Novo Nordisk INvestigational Site
      • Bornova-IZMIR, Turkey, 35100
        • Novo Nordisk INvestigational Site
      • Izmit, Turkey, 41380
        • Novo Nordisk INvestigational Site
      • Samsun, Turkey
        • Novo Nordisk INvestigational Site
      • Donetsk, Ukraine, 83045
        • Novo Nordisk INvestigational Site
      • Lviv, Ukraine, 79044
        • Novo Nordisk INvestigational Site
      • Leicester, United Kingdom, LE1 5WW
        • Novo Nordisk INvestigational Site
      • London, United Kingdom, SE1 7EH
        • Novo Nordisk INvestigational Site
      • Oxford, United Kingdom, OX3 9DU
        • Novo Nordisk INvestigational Site
    • Arizona
      • Phoenix, Arizona, United States, 85016-7710
        • Novo Nordisk INvestigational Site
    • California
      • Long Beach, California, United States, 90806
        • Novo Nordisk INvestigational Site
      • Orange, California, United States, 92868
        • Novo Nordisk INvestigational Site
    • District of Columbia
      • Washington, District of Columbia, United States, 20010-2978
        • Novo Nordisk INvestigational Site
    • Florida
      • Orlando, Florida, United States, 32827
        • Novo Nordisk INvestigational Site
      • Tampa, Florida, United States, 33607
        • Novo Nordisk INvestigational Site
    • Idaho
      • Boise, Idaho, United States, 83712
        • Novo Nordisk INvestigational Site
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Novo Nordisk INvestigational Site
    • Louisiana
      • New Orleans, Louisiana, United States, 70118-5720
        • Novo Nordisk INvestigational Site
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Novo Nordisk INvestigational Site
    • Minnesota
      • Minneapolis, Minnesota, United States, 55404
        • Novo Nordisk INvestigational Site
    • Nebraska
      • Omaha, Nebraska, United States, 68198-6828
        • Novo Nordisk INvestigational Site
    • New York
      • New Hyde Park, New York, United States, 11040
        • Novo Nordisk INvestigational Site
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Novo Nordisk INvestigational Site
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Novo Nordisk INvestigational Site
      • Dayton, Ohio, United States, 45404
        • Novo Nordisk INvestigational Site
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Novo Nordisk INvestigational Site
      • Philadelphia, Pennsylvania, United States, 19134
        • Novo Nordisk INvestigational Site
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Novo Nordisk INvestigational Site
    • Tennessee
      • Nashville, Tennessee, United States, 37232-9830
        • Novo Nordisk INvestigational Site
    • Texas
      • Dallas, Texas, United States, 75235
        • Novo Nordisk INvestigational Site
      • Houston, Texas, United States, 77030
        • Novo Nordisk INvestigational Site
    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • Novo Nordisk INvestigational Site
    • Washington
      • Spokane, Washington, United States, 99204
        • Novo Nordisk INvestigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 9 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: N8-GP
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.
Other Names:
  • NNC 0129-0000-1003
  • N8-GP

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Inhibitory Antibodies Against Coagulation Factor VIII (FVIII) ≥0.6 Bethesda Units
Time Frame: 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.
During the main phase of the trial (from 0-26 weeks of treatment)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Frequency of Adverse Events Including Serious Adverse Events Reported During the Trial Period
Time Frame: 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.
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 When Used for Treatment of Bleeding Episodes and Assessed as: Excellent, Good, Moderate, or None
Time Frame: 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.
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)
Number of Bleeding Episodes During Prophylactic Treatment With N8-GP (Annualised Bleeding Rate)
Time Frame: 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.
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)
Consumption of N8-GP Per Bleeding Episode (Number of Injections)
Time Frame: 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.
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)
Consumption of N8-GP Per Bleeding Episode (U/kg)
Time Frame: 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.
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)
Consumption of N8-GP During Prophylaxis (Number of Injections)
Time Frame: 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.
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)
Consumption of N8-GP During Prophylaxis (U/kg Per Month)
Time Frame: 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])
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)
Consumption of N8-GP During Prophylaxis (U/kg Per Year)
Time Frame: 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)
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)
Incremental Recovery (Defined as the Peak Level Recorded 60 Min After End of Injection) Evaluated for Previous FVIII Product
Time Frame: 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.
2-6 weeks prior to initial dosing with N8-GP and up to 30 hours after administration of previous FVIII product
Incremental Recovery (Defined as the Peak Level Recorded 60 Min After End of Injection) Evaluated for N8-GP
Time Frame: 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.
From 1 hour prior to and up to 96 hours after initial administration of N8-GP
Area Under the Curve Evaluated for Previous FVIII Product
Time Frame: 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.
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 Evaluated for N8-GP
Time Frame: 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.
From 1 hour prior to and up to 96 hours after initial administration of N8-GP
Terminal Half-life Evaluated for Previous FVIII Product
Time Frame: 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.
2-6 weeks prior to initial dosing with N8-GP and up to 30 hours after administration of previous FVIII product
Terminal Half-life Evaluated for N8-GP
Time Frame: 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.
From 1 hour prior to and up to 96 hours after initial administration of N8-GP
Clearance Evaluated for Previous FVIII Product
Time Frame: 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.
2-6 weeks prior to initial dosing with N8-GP and up to 30 hours after administration of previous FVIII product
Clearance Evaluated for N8-GP
Time Frame: 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.
From 1 hour prior to and up to 96 hours after initial administration of N8-GP.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 20, 2013

Primary Completion (Actual)

September 15, 2014

Study Completion (Actual)

September 28, 2018

Study Registration Dates

First Submitted

November 9, 2012

First Submitted That Met QC Criteria

November 16, 2012

First Posted (Estimate)

November 22, 2012

Study Record Updates

Last Update Posted (Actual)

November 23, 2020

Last Update Submitted That Met QC Criteria

November 3, 2020

Last Verified

November 1, 2020

More Information

Terms related to this study

Other Study ID Numbers

  • NN7088-3885
  • U1111-1129-6009 (Other Identifier: WHO)
  • 2012-001711-23 (EudraCT Number)
  • JapicCTI-132214 (Registry Identifier: JAPIC)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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