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

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02994407
• Collaborator: (none)
• Enrollment: 50
• Locations: 19
• Arm: 1
• Actual Duration (Months): 20.5
• Patients Per Site: 2.6
• Patients Per Site Per Month: 0.1

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Congenital Bleeding Disorder; Haemophilia A	Drug: turoctocog alfa pegol	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safety, Tolerability, and Pharmacokinetics Study of Single and Multiple Subcutaneous Doses of Turoctocog Alfa Pegol in Patients With Haemophilia A
• Actual Study Start Date: Jan 30, 2017
• Actual Primary Completion Date: Oct 15, 2018
• Actual Study Completion Date: Oct 15, 2018

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Number of adverse events [Day 0-Day 28]

   Count and % of Adverse events

Secondary Outcome Measures

1. Cmax [0-144 hours]

   Calculated based on plasma FVIII activity measured in blood.

2. Incidence of FVIII inhibitors above or equal to 0.6 BU [Day 0-Day 28]

   Count of presence of inhibitors

3. Area under the activity time curve from 0 to infinity [0-144 hours]

   Calculated based on plasma FVIII activity measured in blood.

4. Area under the activity time curve from 0 to t [0-144 hours]

   Calculated based on plasma FVIII activity measured in blood.

5. Area under the activity time curve from 0 to last [0-144 hours]

   Calculated based on plasma FVIII activity measured in blood.

6. tmax- time to maximal FVIII activity [0-144 hours]

   Calculated based on plasma FVIII activity measured in blood.

7. Cmin -the minimal FVIII activity [0-144 hours]

   Calculated based on plasma FVIII activity measured in blood.

8. tmin - time to minimal FVIII activity [0-144 hours]

   Calculated based on plasma FVIII activity measured in blood.

9. Css, min - the minimum FVIII activity at steady state [0-144 hours]

   Calculated based on plasma FVIII activity measured in blood.

10. Css, max - the maximal FVIII activity at steady state [0-144 hours]

    Calculated based on plasma FVIII activity measured in blood.

11. Css - the mean FVIII activity at steady state [0-144 hours]

    Calculated based on plasma FVIII activity measured in blood.

12. Racc - accumulation ratio [0-144 hours]

    Calculated based on plasma FVIII activity measured in blood.

13. t½ - terminal half-life [0-144 hours]

    Calculated based on plasma FVIII activity measured in blood.

14. CL - total plasma clearance of drug after intravenous administration [0-144 hours]

    Calculated based on plasma FVIII activity measured in blood.

15. Vz -apparent volume of distribution during terminal phase [0-144 hours]

    Calculated based on plasma FVIII activity measured in blood.

16. Vss - apparent volume of distribution during steady state [0-144 hours]

    Calculated based on plasma FVIII activity measured in blood.

17. MRT - mean residence time [0-144 hours]

    Calculated based on plasma FVIII activity measured in blood.

18. Injection site reactions [Day 0 - day 28]

    Count of reactions

19. Number of treatment requiring bleeding episodes [Day 0 - day 120]

    Count of episodes

20. Consumption of FVIII [Day 0 - day 120]

    Measured in IU

21. Change in Coagulation parameters, fibrinogen [Day 0, day 7]

    Measured in g/L

22. Change in Coagulation parameters, antithrombin [Day 0, day 7]

    Measured in %

23. Change in Coagulation parameters, international normalised ratio [Day 0, day 7]

    Measured in INR

24. Change in Coagulation parameters, activated partial thromboplastin time [Day 0, day 7]

    Measured in sec.

25. Change in Coagulation parameters, von Willebrand Factor [Day 0, day 7]

    Measured in %

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Orlando	Florida	United States	32827
2	Novo Nordisk Investigational Site	Iowa City	Iowa	United States	52242
3	Novo Nordisk Investigational Site	East Lansing	Michigan	United States	48823
4	Novo Nordisk Investigational Site	Cleveland	Ohio	United States	44106
5	Novo Nordisk Investigational Site	Dayton	Ohio	United States	45404
6	Novo Nordisk Investigational Site	Charleston	South Carolina	United States	29425-0001
7	Novo Nordisk Investigational Site	Norfolk	Virginia	United States	23507
8	Novo Nordisk Investigational Site	Milwaukee	Wisconsin	United States	53226
9	Novo Nordisk Investigational Site	Innsbruck		Austria	A 6020
10	Novo Nordisk Investigational Site	Wien		Austria	1090
11	Novo Nordisk Investigational Site	Nantes Cedex 1		France	44093
12	Novo Nordisk Investigational Site	Berlin		Germany	10249
13	Novo Nordisk Investigational Site	Duisburg		Germany	47051
14	Novo Nordisk Investigational Site	Homburg		Germany	66421
15	Novo Nordisk Investigational Site	Shinjuku-ku, Tokyo		Japan	160 0023
16	Novo Nordisk Investigational Site	Tokyo		Japan	167-0035
17	Novo Nordisk Investigational Site	Belgrade		Serbia	11000
18	Novo Nordisk Investigational Site	Belgrade		Serbia	11070
19	Novo Nordisk Investigational Site	Novi Sad		Serbia	21000

Sponsors and Collaborators

• Novo Nordisk A/S

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT02994407
• Other Study ID Numbers: NN7170-4213; U1111-1183-5111; 2016-002396-99; JapicCTI-173683
• First Posted: Dec 15, 2016
• Last Update Posted: Feb 5, 2020
• Last Verified: Jan 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Hemostatic Disorders; Hemophilia A; Blood Coagulation Disorders

Study Results

No Results Posted as of Feb 5, 2020