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Safety, Tolerability, and Pharmacokinetics Study of Turoctocog Alfa Pegol Injected Under the Skin in Patients With Haemophilia A (alleviate 1)

Primary Purpose

Congenital Bleeding Disorder, Haemophilia A

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
turoctocog alfa pegol
Sponsored by
Novo Nordisk A/S
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Congenital Bleeding Disorder

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Male, age above or equal to 18 years at the time of signing informed consent,(part A).
  • Male, age above or equal to 12 years at the time of signing informed consent,(part B).
  • Diagnosis of congenital haemophilia A based on medical records (FVIII activity <1%).
  • History of more than 150 exposure days to any FVIII containing products.

Exclusion Criteria:

  • Previous participation in this trial. Participation is defined as signed informed consent.

(Patients who have completed part A are allowed to also participate in part B. If so, a separate informed consent covering part B must be signed.)

  • Immune compromised patients due to human immunodeficiency virus (HIV) infection (defined as viral load greater than or equal to 400.000 copies/mL and/or cluster of differentiation 4+ (CD4+) lymphocyte count less than or equal to 200/μL performed at screening or defined by medical records no older than 6 months)
  • Any history of FVIII inhibitors (defined by medical records within 8 years of randomisation)
  • Inhibitors to FVIII (greater than or equal to 0.6 Bethesda unit (BU)) at screening, measured by Nijmegen modified Bethesda method at central laboratory.

Sites / Locations

  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

N8-GP s.c.

Arm Description

Outcomes

Primary Outcome Measures

Number of adverse events
Count and % of Adverse events

Secondary Outcome Measures

Cmax
Calculated based on plasma FVIII activity measured in blood.
Incidence of FVIII inhibitors above or equal to 0.6 BU
Count of presence of inhibitors
Area under the activity time curve from 0 to infinity
Calculated based on plasma FVIII activity measured in blood.
Area under the activity time curve from 0 to t
Calculated based on plasma FVIII activity measured in blood.
Area under the activity time curve from 0 to last
Calculated based on plasma FVIII activity measured in blood.
tmax- time to maximal FVIII activity
Calculated based on plasma FVIII activity measured in blood.
Cmin -the minimal FVIII activity
Calculated based on plasma FVIII activity measured in blood.
tmin - time to minimal FVIII activity
Calculated based on plasma FVIII activity measured in blood.
Css, min - the minimum FVIII activity at steady state
Calculated based on plasma FVIII activity measured in blood.
Css, max - the maximal FVIII activity at steady state
Calculated based on plasma FVIII activity measured in blood.
Css - the mean FVIII activity at steady state
Calculated based on plasma FVIII activity measured in blood.
Racc - accumulation ratio
Calculated based on plasma FVIII activity measured in blood.
t½ - terminal half-life
Calculated based on plasma FVIII activity measured in blood.
CL - total plasma clearance of drug after intravenous administration
Calculated based on plasma FVIII activity measured in blood.
Vz -apparent volume of distribution during terminal phase
Calculated based on plasma FVIII activity measured in blood.
Vss - apparent volume of distribution during steady state
Calculated based on plasma FVIII activity measured in blood.
MRT - mean residence time
Calculated based on plasma FVIII activity measured in blood.
Injection site reactions
Count of reactions
Number of treatment requiring bleeding episodes
Count of episodes
Consumption of FVIII
Measured in IU
Change in Coagulation parameters, fibrinogen
Measured in g/L
Change in Coagulation parameters, antithrombin
Measured in %
Change in Coagulation parameters, international normalised ratio
Measured in INR
Change in Coagulation parameters, activated partial thromboplastin time
Measured in sec.
Change in Coagulation parameters, von Willebrand Factor
Measured in %

Full Information

First Posted
December 13, 2016
Last Updated
January 31, 2020
Sponsor
Novo Nordisk A/S
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1. Study Identification

Unique Protocol Identification Number
NCT02994407
Brief Title
Safety, Tolerability, and Pharmacokinetics Study of Turoctocog Alfa Pegol Injected Under the Skin in Patients With Haemophilia A
Acronym
alleviate 1
Official Title
Safety, Tolerability, and Pharmacokinetics Study of Single and Multiple Subcutaneous Doses of Turoctocog Alfa Pegol in Patients With Haemophilia A
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
January 30, 2017 (Actual)
Primary Completion Date
October 15, 2018 (Actual)
Study Completion Date
October 15, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novo Nordisk A/S

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The trial is conducted in Asia, Europe and North America. The aim of the study is to evaluate the safety of administration under the skin of turoctocog alfa pegol (SC N8-GP) in patients with severe haemophilia A.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Congenital Bleeding Disorder, Haemophilia A

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
N8-GP s.c.
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
turoctocog alfa pegol
Intervention Description
Part A: Participants will receive a single dose of turoctocog alfa pegol, administered subcutaneously (under the skin), at a dose of 12.5, 25 or 50 U/kg. Part B: Participants will receive a daily dose of turoctocog alfa pegol, as identified in Part A, as a subcutaneous (under the skin) injection for a period of 3 months.
Primary Outcome Measure Information:
Title
Number of adverse events
Description
Count and % of Adverse events
Time Frame
Day 0-Day 28
Secondary Outcome Measure Information:
Title
Cmax
Description
Calculated based on plasma FVIII activity measured in blood.
Time Frame
0-144 hours
Title
Incidence of FVIII inhibitors above or equal to 0.6 BU
Description
Count of presence of inhibitors
Time Frame
Day 0-Day 28
Title
Area under the activity time curve from 0 to infinity
Description
Calculated based on plasma FVIII activity measured in blood.
Time Frame
0-144 hours
Title
Area under the activity time curve from 0 to t
Description
Calculated based on plasma FVIII activity measured in blood.
Time Frame
0-144 hours
Title
Area under the activity time curve from 0 to last
Description
Calculated based on plasma FVIII activity measured in blood.
Time Frame
0-144 hours
Title
tmax- time to maximal FVIII activity
Description
Calculated based on plasma FVIII activity measured in blood.
Time Frame
0-144 hours
Title
Cmin -the minimal FVIII activity
Description
Calculated based on plasma FVIII activity measured in blood.
Time Frame
0-144 hours
Title
tmin - time to minimal FVIII activity
Description
Calculated based on plasma FVIII activity measured in blood.
Time Frame
0-144 hours
Title
Css, min - the minimum FVIII activity at steady state
Description
Calculated based on plasma FVIII activity measured in blood.
Time Frame
0-144 hours
Title
Css, max - the maximal FVIII activity at steady state
Description
Calculated based on plasma FVIII activity measured in blood.
Time Frame
0-144 hours
Title
Css - the mean FVIII activity at steady state
Description
Calculated based on plasma FVIII activity measured in blood.
Time Frame
0-144 hours
Title
Racc - accumulation ratio
Description
Calculated based on plasma FVIII activity measured in blood.
Time Frame
0-144 hours
Title
t½ - terminal half-life
Description
Calculated based on plasma FVIII activity measured in blood.
Time Frame
0-144 hours
Title
CL - total plasma clearance of drug after intravenous administration
Description
Calculated based on plasma FVIII activity measured in blood.
Time Frame
0-144 hours
Title
Vz -apparent volume of distribution during terminal phase
Description
Calculated based on plasma FVIII activity measured in blood.
Time Frame
0-144 hours
Title
Vss - apparent volume of distribution during steady state
Description
Calculated based on plasma FVIII activity measured in blood.
Time Frame
0-144 hours
Title
MRT - mean residence time
Description
Calculated based on plasma FVIII activity measured in blood.
Time Frame
0-144 hours
Title
Injection site reactions
Description
Count of reactions
Time Frame
Day 0 - day 28
Title
Number of treatment requiring bleeding episodes
Description
Count of episodes
Time Frame
Day 0 - day 120
Title
Consumption of FVIII
Description
Measured in IU
Time Frame
Day 0 - day 120
Title
Change in Coagulation parameters, fibrinogen
Description
Measured in g/L
Time Frame
Day 0, day 7
Title
Change in Coagulation parameters, antithrombin
Description
Measured in %
Time Frame
Day 0, day 7
Title
Change in Coagulation parameters, international normalised ratio
Description
Measured in INR
Time Frame
Day 0, day 7
Title
Change in Coagulation parameters, activated partial thromboplastin time
Description
Measured in sec.
Time Frame
Day 0, day 7
Title
Change in Coagulation parameters, von Willebrand Factor
Description
Measured in %
Time Frame
Day 0, day 7

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male, age above or equal to 18 years at the time of signing informed consent,(part A). Male, age above or equal to 12 years at the time of signing informed consent,(part B). Diagnosis of congenital haemophilia A based on medical records (FVIII activity <1%). History of more than 150 exposure days to any FVIII containing products. Exclusion Criteria: Previous participation in this trial. Participation is defined as signed informed consent. (Patients who have completed part A are allowed to also participate in part B. If so, a separate informed consent covering part B must be signed.) Immune compromised patients due to human immunodeficiency virus (HIV) infection (defined as viral load greater than or equal to 400.000 copies/mL and/or cluster of differentiation 4+ (CD4+) lymphocyte count less than or equal to 200/μL performed at screening or defined by medical records no older than 6 months) Any history of FVIII inhibitors (defined by medical records within 8 years of randomisation) Inhibitors to FVIII (greater than or equal to 0.6 Bethesda unit (BU)) at screening, measured by Nijmegen modified Bethesda method at central laboratory.
Facility Information:
Facility Name
Novo Nordisk Investigational Site
City
Orlando
State/Province
Florida
ZIP/Postal Code
32827
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
East Lansing
State/Province
Michigan
ZIP/Postal Code
48823
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45404
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425-0001
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Innsbruck
ZIP/Postal Code
A 6020
Country
Austria
Facility Name
Novo Nordisk Investigational Site
City
Wien
ZIP/Postal Code
1090
Country
Austria
Facility Name
Novo Nordisk Investigational Site
City
Nantes Cedex 1
ZIP/Postal Code
44093
Country
France
Facility Name
Novo Nordisk Investigational Site
City
Berlin
ZIP/Postal Code
10249
Country
Germany
Facility Name
Novo Nordisk Investigational Site
City
Duisburg
ZIP/Postal Code
47051
Country
Germany
Facility Name
Novo Nordisk Investigational Site
City
Homburg
ZIP/Postal Code
66421
Country
Germany
Facility Name
Novo Nordisk Investigational Site
City
Shinjuku-ku, Tokyo
ZIP/Postal Code
160 0023
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Tokyo
ZIP/Postal Code
167-0035
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
Novo Nordisk Investigational Site
City
Belgrade
ZIP/Postal Code
11070
Country
Serbia
Facility Name
Novo Nordisk Investigational Site
City
Novi Sad
ZIP/Postal Code
21000
Country
Serbia

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
Citations:
PubMed Identifier
31618804
Citation
Klamroth R, Feistritzer C, Friedrich U, Lentz SR, Reichwald K, Zak M, Chowdary P. Pharmacokinetics, immunogenicity, safety, and preliminary efficacy of subcutaneous turoctocog alfa pegol in previously treated patients with severe hemophilia A (alleviate 1). J Thromb Haemost. 2020 Feb;18(2):341-351. doi: 10.1111/jth.14660. Epub 2019 Nov 15.
Results Reference
derived

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Safety, Tolerability, and Pharmacokinetics Study of Turoctocog Alfa Pegol Injected Under the Skin in Patients With Haemophilia A

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