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

Congenital Bleeding Disorder Clinical Trial

— alleviate 1  

Official title:

Safety, Tolerability, and Pharmacokinetics Study of Single and Multiple Subcutaneous Doses of Turoctocog Alfa Pegol in Patients With Haemophilia A

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02994407
• Other study ID #: NN7170-4213
• Secondary ID: U1111-1183-51112
• Status: Completed
• Phase: Phase 1
• Start date: January 30, 2017
• Est. completion date: October 15, 2018

Study information

• Verified date: January 2020
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: October 15, 2018
• Est. primary completion date: October 15, 2018
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• turoctocog alfa pegol
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.

Locations

Country	Name	City	State
Austria	Novo Nordisk Investigational Site	Innsbruck
Austria	Novo Nordisk Investigational Site	Wien
France	Novo Nordisk Investigational Site	Nantes Cedex 1
Germany	Novo Nordisk Investigational Site	Berlin
Germany	Novo Nordisk Investigational Site	Duisburg
Germany	Novo Nordisk Investigational Site	Homburg
Japan	Novo Nordisk Investigational Site	Shinjuku-ku, Tokyo
Japan	Novo Nordisk Investigational Site	Tokyo
Serbia	Novo Nordisk Investigational Site	Belgrade
Serbia	Novo Nordisk Investigational Site	Belgrade
Serbia	Novo Nordisk Investigational Site	Novi Sad
United States	Novo Nordisk Investigational Site	Charleston	South Carolina
United States	Novo Nordisk Investigational Site	Cleveland	Ohio
United States	Novo Nordisk Investigational Site	Dayton	Ohio
United States	Novo Nordisk Investigational Site	East Lansing	Michigan
United States	Novo Nordisk Investigational Site	Iowa City	Iowa
United States	Novo Nordisk Investigational Site	Milwaukee	Wisconsin
United States	Novo Nordisk Investigational Site	Norfolk	Virginia
United States	Novo Nordisk Investigational Site	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Austria,  France,  Germany,  Japan,  Serbia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of adverse events	Count and % of Adverse events	Day 0-Day 28
Secondary	Cmax	Calculated based on plasma FVIII activity measured in blood.	0-144 hours
Secondary	Incidence of FVIII inhibitors above or equal to 0.6 BU	Count of presence of inhibitors	Day 0-Day 28
Secondary	Area under the activity time curve from 0 to infinity	Calculated based on plasma FVIII activity measured in blood.	0-144 hours
Secondary	Area under the activity time curve from 0 to t	Calculated based on plasma FVIII activity measured in blood.	0-144 hours
Secondary	Area under the activity time curve from 0 to last	Calculated based on plasma FVIII activity measured in blood.	0-144 hours
Secondary	tmax- time to maximal FVIII activity	Calculated based on plasma FVIII activity measured in blood.	0-144 hours
Secondary	Cmin -the minimal FVIII activity	Calculated based on plasma FVIII activity measured in blood.	0-144 hours
Secondary	tmin - time to minimal FVIII activity	Calculated based on plasma FVIII activity measured in blood.	0-144 hours
Secondary	Css, min - the minimum FVIII activity at steady state	Calculated based on plasma FVIII activity measured in blood.	0-144 hours
Secondary	Css, max - the maximal FVIII activity at steady state	Calculated based on plasma FVIII activity measured in blood.	0-144 hours
Secondary	Css - the mean FVIII activity at steady state	Calculated based on plasma FVIII activity measured in blood.	0-144 hours
Secondary	Racc - accumulation ratio	Calculated based on plasma FVIII activity measured in blood.	0-144 hours
Secondary	t½ - terminal half-life	Calculated based on plasma FVIII activity measured in blood.	0-144 hours
Secondary	CL - total plasma clearance of drug after intravenous administration	Calculated based on plasma FVIII activity measured in blood.	0-144 hours
Secondary	Vz -apparent volume of distribution during terminal phase	Calculated based on plasma FVIII activity measured in blood.	0-144 hours
Secondary	Vss - apparent volume of distribution during steady state	Calculated based on plasma FVIII activity measured in blood.	0-144 hours
Secondary	MRT - mean residence time	Calculated based on plasma FVIII activity measured in blood.	0-144 hours
Secondary	Injection site reactions	Count of reactions	Day 0 - day 28
Secondary	Number of treatment requiring bleeding episodes	Count of episodes	Day 0 - day 120
Secondary	Consumption of FVIII	Measured in IU	Day 0 - day 120
Secondary	Change in Coagulation parameters, fibrinogen	Measured in g/L	Day 0, day 7
Secondary	Change in Coagulation parameters, antithrombin	Measured in %	Day 0, day 7
Secondary	Change in Coagulation parameters, international normalised ratio	Measured in INR	Day 0, day 7
Secondary	Change in Coagulation parameters, activated partial thromboplastin time	Measured in sec.	Day 0, day 7
Secondary	Change in Coagulation parameters, von Willebrand Factor	Measured in %	Day 0, day 7