Clinical trial NCT02994407: Safety, Tolerability, and Pharmacokinetics Study of Turoctocog Alfa Pegol Injected Under the Skin in Patients With Haemophilia A
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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Congenital Bleeding Disorder
Haemophilia A
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2016-12-15
Enrollment: 50
Sex: MALE
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of adverse events
timeFrame: Day 0-Day 28
Secondary outcomes:
measure: Cmax
timeFrame: 0-144 hours
measure: Incidence of FVIII inhibitors above or equal to 0.6 BU
timeFrame: Day 0-Day 28
measure: Area under the activity time curve from 0 to infinity
timeFrame: 0-144 hours
measure: Area under the activity time curve from 0 to t
timeFrame: 0-144 hours
measure: Area under the activity time curve from 0 to last
timeFrame: 0-144 hours
measure: tmax- time to maximal FVIII activity
timeFrame: 0-144 hours
measure: Cmin -the minimal FVIII activity
timeFrame: 0-144 hours
measure: tmin - time to minimal FVIII activity
timeFrame: 0-144 hours
measure: Css, min - the minimum FVIII activity at steady state
timeFrame: 0-144 hours
measure: Css, max - the maximal FVIII activity at steady state
timeFrame: 0-144 hours
measure: Css - the mean FVIII activity at steady state
timeFrame: 0-144 hours
measure: Racc - accumulation ratio
timeFrame: 0-144 hours
measure: t½ - terminal half-life
timeFrame: 0-144 hours
measure: CL - total plasma clearance of drug after intravenous administration
timeFrame: 0-144 hours
measure: Vz -apparent volume of distribution during terminal phase
timeFrame: 0-144 hours
measure: Vss - apparent volume of distribution during steady state
timeFrame: 0-144 hours
measure: MRT - mean residence time
timeFrame: 0-144 hours
measure: Injection site reactions
timeFrame: Day 0 - day 28
measure: Number of treatment requiring bleeding episodes
timeFrame: Day 0 - day 120
measure: Consumption of FVIII
timeFrame: Day 0 - day 120
measure: Change in Coagulation parameters, fibrinogen
timeFrame: Day 0, day 7
measure: Change in Coagulation parameters, antithrombin
timeFrame: Day 0, day 7
measure: Change in Coagulation parameters, international normalised ratio
timeFrame: Day 0, day 7
measure: Change in Coagulation parameters, activated partial thromboplastin time
timeFrame: Day 0, day 7
measure: Change in Coagulation parameters, von Willebrand Factor
timeFrame: Day 0, day 7
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Iowa City
country: United States
facility: Novo Nordisk Investigational Site
state: Iowa
city: East Lansing
country: United States
facility: Novo Nordisk Investigational Site
state: Michigan
city: Cleveland
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Dayton
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Charleston
country: United States
facility: Novo Nordisk Investigational Site
state: South Carolina
city: Norfolk
country: United States
facility: Novo Nordisk Investigational Site
state: Virginia
city: Milwaukee
country: United States
facility: Novo Nordisk Investigational Site
state: Wisconsin
city: Innsbruck
country: Austria
facility: Novo Nordisk Investigational Site
city: Wien
country: Austria
facility: Novo Nordisk Investigational Site
city: Nantes Cedex 1
country: France
facility: Novo Nordisk Investigational Site
city: Berlin
country: Germany
facility: Novo Nordisk Investigational Site
city: Duisburg
country: Germany
facility: Novo Nordisk Investigational Site
city: Homburg
country: Germany
facility: Novo Nordisk Investigational Site
city: Shinjuku-ku, Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Belgrade
country: Serbia
facility: Novo Nordisk Investigational Site
city: Belgrade
country: Serbia
facility: Novo Nordisk Investigational Site
city: Novi Sad
country: Serbia
facility: Novo Nordisk Investigational Site
Study officials:
References:
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.