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

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

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.

Study Overview

• Status: Completed
• Conditions: Congenital Bleeding Disorder; Haemophilia A
• Intervention / Treatment: Drug: turoctocog alfa pegol

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, A 6020
    • Novo Nordisk Investigational Site
  • Wien, Austria, 1090
    • Novo Nordisk Investigational Site
• France
  • Nantes Cedex 1, France, 44093
    • Novo Nordisk Investigational Site
• Germany
  • Berlin, Germany, 10249
    • Novo Nordisk Investigational Site
  • Duisburg, Germany, 47051
    • Novo Nordisk Investigational Site
  • Homburg, Germany, 66421
    • Novo Nordisk Investigational Site
• Japan
  • Shinjuku-ku, Tokyo, Japan, 160 0023
    • Novo Nordisk Investigational Site
  • Tokyo, Japan, 167-0035
    • Novo Nordisk Investigational Site
• Serbia
  • Belgrade, Serbia, 11000
    • Novo Nordisk Investigational Site
  • Belgrade, Serbia, 11070
    • Novo Nordisk Investigational Site
  • Novi Sad, Serbia, 21000
    • Novo Nordisk Investigational Site
• United States
  • Florida
    • Orlando, Florida, United States, 32827
      • Novo Nordisk Investigational Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Novo Nordisk Investigational Site
  • Michigan
    • East Lansing, Michigan, United States, 48823
      • Novo Nordisk Investigational Site
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Novo Nordisk Investigational Site
    • Dayton, Ohio, United States, 45404
      • Novo Nordisk Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States, 29425-0001
      • Novo Nordisk Investigational Site
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Novo Nordisk Investigational Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: N8-GP s.c.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of adverse events	Count and % of Adverse events	Day 0-Day 28

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2017
• Primary Completion (Actual): October 15, 2018
• Study Completion (Actual): October 15, 2018

Study Registration Dates

• First Submitted: December 13, 2016
• First Submitted That Met QC Criteria: December 13, 2016
• First Posted (Estimate): December 15, 2016

Study Record Updates

• Last Update Posted (Actual): February 5, 2020
• Last Update Submitted That Met QC Criteria: January 31, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Hemostatic Disorders; Hemophilia A; Blood Coagulation Disorders
• Other Study ID Numbers: NN7170-4213; U1111-1183-5111 (Other Identifier: WHO); 2016-002396-99 (EudraCT Number); JapicCTI-173683 (Registry Identifier: JAPIC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No