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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)

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ClinicalTrials.gov Identifier: NCT01731600
Recruitment Status : Completed
First Posted : November 22, 2012
Results First Posted : October 30, 2019
Last Update Posted : August 4, 2020
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Congenital Bleeding Disorder Haemophilia A Drug: turoctocog alfa pegol Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 68 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : February 20, 2013
Actual Primary Completion Date : September 15, 2014
Actual Study Completion Date : September 28, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hemophilia

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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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])

  8. 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)

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.



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Ages Eligible for Study:   up to 11 Years   (Child)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01731600


Locations
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Sponsors and Collaborators
Novo Nordisk A/S
Investigators
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Study Director: Global Clinical Registry (GCR, 1452) Novo Nordisk A/S
  Study Documents (Full-Text)

Documents provided by Novo Nordisk A/S:
Study Protocol  [PDF] November 13, 2015

Additional Information:
Publications of Results:
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Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT01731600    
Other Study ID Numbers: NN7088-3885
U1111-1129-6009 ( Other Identifier: WHO )
2012-001711-23 ( EudraCT Number )
JapicCTI-132214 ( Registry Identifier: JAPIC )
First Posted: November 22, 2012    Key Record Dates
Results First Posted: October 30, 2019
Last Update Posted: August 4, 2020
Last Verified: July 2020
Additional relevant MeSH terms:
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Hemostatic Disorders
Hemophilia A
Blood Coagulation Disorders
Blood Coagulation Disorders, Inherited
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Vascular Diseases
Cardiovascular Diseases