A Trial Evaluating the Efficacy and Safety of Prophylactic Administration of Concizumab in Haemophilia A and B Patients With Inhibitors

Congenital Bleeding Disorder Clinical Trial

— explorer™4  

Official title:

A Multi-Centre, Randomised, Open-Label, Controlled Trial Evaluating the Efficacy and Safety of Prophylactic Administration of Concizumab in Haemophilia A and B Patients With Inhibitors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03196284
• Other study ID #: NN7415-4310
• Secondary ID: U1111-1179-29252
• Status: Completed
• Phase: Phase 2
• Start date: August 10, 2017
• Est. completion date: January 31, 2020

Study information

• Verified date: September 2021
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial is conducted in Africa, Asia, Europe and North America. The aim of the trial is to assess the efficacy of concizumab administered s.c. (subcutaneously, under the skin) once daily in preventing bleeding episodes in haemophilia A and B patients with inhibitors.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: January 31, 2020
• Est. primary completion date: September 19, 2018
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria: - Informed consent obtained before any trial related activities. Trial related activities are any procedures that are carried out as part of the trial, including activities to determine the suitability for the trial - Male haemophilia A or B patients with inhibitors aged 18 years or older at the time of signing informed consent - Patients currently in need of treatment with bypassing agents Exclusion Criteria: - Known or suspected hypersensitivity to trial product(s) or related products - Known inherited or acquired bleeding disorder other than haemophilia - Ongoing or planned immune tolerance induction therapy or prophylaxis with FVIII or FIX

Related Conditions & MeSH terms

• Blood Coagulation Disorders
• Congenital Bleeding Disorder
• Haemophilia A With Inhibitors
• Haemophilia B With Inhibitors
• Hemophilia A
• Hemophilia B
• Hemostatic Disorders

Intervention

Drug:
• Concizumab
A loading dose of 0.5 mg/kg will be given as the first dose, followed by 0.15 mg/kg (with potential stepwise dose escalation to 0.25 mg/kg) administered daily s.c. (subcutaneously, under the skin). Treatment duration is 24 weeks in the main trial, and up to 52 weeks in the extension phase
• Eptacog alfa
A single dose of 90 µg/kg eptacog alfa one week after dosing with concizumab. On-demand treatment during bleeding episodes in both treatment arms

Locations

Country	Name	City	State
Austria	Novo Nordisk Investigational Site	Wien
Canada	Novo Nordisk Investigational Site	Toronto	Ontario
Croatia	Novo Nordisk Investigational Site	Zagreb
Denmark	Novo Nordisk Investigational Site	Århus N
Greece	Novo Nordisk Investigational Site	Athens
Israel	Novo Nordisk Investigational Site	Tel-Hashomer
Italy	Novo Nordisk Investigational Site	Firenze
Italy	Novo Nordisk Investigational Site	Milano
Japan	Novo Nordisk Investigational Site	Aichi
Japan	Novo Nordisk Investigational Site	Nara
Japan	Novo Nordisk Investigational Site	Tokyo
Malaysia	Novo Nordisk Investigational Site	Georgetown, Penang
Malaysia	Novo Nordisk Investigational Site	Kota Kinabalu
Spain	Novo Nordisk Investigational Site	Madrid
Spain	Novo Nordisk Investigational Site	Sevilla
Sweden	Novo Nordisk Investigational Site	Solna
Ukraine	Novo Nordisk Investigational Site	Lviv
United Kingdom	Novo Nordisk Investigational Site	London
United Kingdom	Novo Nordisk Investigational Site	Sheffield
United States	Novo Nordisk Investigational Site	Indianapolis	Indiana
United States	Novo Nordisk Investigational Site	Iowa City	Iowa
United States	Novo Nordisk Investigational Site	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Austria,  Canada,  Croatia,  Denmark,  Greece,  Israel,  Italy,  Japan,  Malaysia,  Spain,  Sweden,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Number of Bleeding Episodes	The number of bleeding episodes that were treated during at least 24 weeks from treatment onset (week 0) are presented.	During at least 24 weeks from treatment onset (week 0)
Secondary	The Number of Bleeding Episodes	The number of bleeding episodes that were treated during at least 76 weeks from treatment onset (week 0) are presented. This outcome measure is applicable for only 'Concizumab' treatment arm.	During at least 76 weeks from treatment onset (week 0)
Secondary	The Number of Spontaneous Bleeding Episodes	Bleeds that were not linked to a specific, known action or event are called spontaneous bleeding episodes. The number of spontaneous bleeding episodes that were treated during at least 24 weeks from treatment onset (week 0) are presented. The data is presented per the last dose level which the participants have reached at the time of assessment.	During at least 24 weeks from treatment onset (week 0)
Secondary	The Number of Spontaneous Bleeding Episodes	Bleeds that were not linked to a specific, known action or event are called spontaneous bleeding episodes. The number of spontaneous bleeding episodes that were treated during at least 76 weeks from treatment onset (week 0) are presented. The data is presented per the last dose level which the participants have reached at the time of assessment.	During at least 76 weeks from treatment onset (week 0)
Secondary	Number of Treatment-emergent Adverse Events (TEAEs) During at Least 24 Weeks From Treatment Onset	An adverse event (AE) was any untoward medical occurrence in a participant administered a medicinal product, and which does not necessarily had a causal relationship with this treatment. A TEAE was defined as an event that had onset from the first exposure to treatment until the last visit in the trial. Number of TEAEs that occurred during at least 24 weeks from treatment onset (week 0) are presented. The data is presented per the dose level which the participants have reached at the time of event.	During at least 24 weeks from treatment onset (week 0)
Secondary	Number of Treatment-emergent Adverse Events (TEAEs) During at Least 76 Weeks From Treatment Onset	An adverse event (AE) was any untoward medical occurrence in a participant administered a medicinal product, and which does not necessarily had a causal relationship with this treatment. A TEAE was defined as an event that had onset from the first exposure to treatment until the last visit in the trial. Number of TEAEs that occurred during at least 76 weeks from treatment onset (week 0) are presented. The data is presented per the dose level which the participants have reached at the time of event.	During at least 76 weeks from treatment onset (week 0)
Secondary	Number of Treatment-emergent Adverse Events (TEAEs) Within 24 Hours After Eptacog Alfa Administration	An adverse event (AE) was any untoward medical occurrence in a participant administered a medicinal product, and which does not necessarily had a causal relationship with this treatment. A TEAE was defined as an event that had onset from the first exposure to treatment until the last visit in the trial. Number of TEAEs that occurred within 24 hours after eptacog alfa administration are presented. This outcome measure is applicable only for 'Eptacog alfa' treatment arm.	Within 24 hours after eptacog alfa administration
Secondary	Occurrence of Anti-concizumab Antibodies During at Least 24 Weeks From Treatment Onset	Occurrence of anti-concizumab antibodies during at least 24 weeks from treatment onset (week 0) is presented. This outcome measure is applicable for only 'Concizumab' treatment arm.	During at least 24 weeks from treatment onset (week 0)
Secondary	Occurrence of Anti-concizumab Antibodies During at Least 76 Weeks From Treatment Onset	Occurrence of anti-concizumab antibodies during at least 76 weeks from treatment onset (week 0) is presented. This outcome measure is applicable for only 'Concizumab' treatment arm.	During at least 76 weeks from treatment onset (week 0)
Secondary	Change in Fibrinogen	Change in fibrinogen during at least 24 weeks from treatment onset (week 0) is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.	During at least 24 weeks from treatment onset (week 0)
Secondary	Change in Fibrinogen	Change in fibrinogen during at least 76 weeks from treatment onset (week 0) is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.	During at least 76 weeks from treatment onset (week 0)
Secondary	Change in D-dimer	Change in D-dimer during at least 24 weeks from treatment onset (week 0) is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.	During at least 24 weeks from treatment onset (week 0)
Secondary	Change in D-dimer	Change in D-dimer during at least 76 weeks from treatment onset (week 0) is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.	During at least 76 weeks from treatment onset (week 0)
Secondary	Change in Prothrombin Fragment 1 + 2 (F1 + 2)	Change in F1 + 2 during at least 24 weeks from treatment onset (week 0) is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.	During at least 24 weeks from treatment onset (week 0)
Secondary	Change in Prothrombin Fragment 1 + 2 (F1 + 2)	Change in F1 + 2 during at least 76 weeks from treatment onset (week 0) is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.	During at least 76 weeks from treatment onset (week 0)
Secondary	Change in Prothrombin Time (PT)	Change in PT during at least 24 weeks from treatment onset (week 0) is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.	During at least 24 weeks from treatment onset (week 0)
Secondary	Change in Prothrombin Time (PT)	Change in PT during at least 76 weeks from treatment onset (week 0) is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.	During at least 76 weeks from treatment onset (week 0)
Secondary	Change in Activated Partial Thromboplastin Time (APTT)	Change in APTT during at least 24 weeks from treatment onset (week 0) is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.	During at least 24 weeks from treatment onset (week 0)
Secondary	Change in Activated Partial Thromboplastin Time (APTT)	Change in APTT during at least 76 weeks from treatment onset (week 0) is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.	During at least 76 weeks from treatment onset (week 0)
Secondary	Change in Anti-thrombin (AT)	Change in AT during at least 24 weeks from treatment onset (week 0) is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.	During at least 24 weeks from treatment onset (week 0)
Secondary	Change in Anti-thrombin (AT)	Change in AT after at least 76 weeks from treatment onset (week 0) is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.	After at least 76 weeks from treatment onset (week 0)
Secondary	Concentration of Concizumab	Concentration of concizumab prior to the last dose administration at 24 weeks is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.	Prior to the last dose administration at 24 weeks
Secondary	Concentration of Concizumab	Concentration of concizumab prior to the last dose administration after atleast 76 weeks is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.	Prior to the last dose administration after atleast 76 weeks
Secondary	Free Tissue Factor Pathway Inhibitor (TFPI) Concentration Value	Free TFPI (TFPI not bound to concizumab) concentration value prior to the last dose administration at 24 weeks is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.	Prior to the last dose administration at 24 weeks
Secondary	Free Tissue Factor Pathway Inhibitor (TFPI) Concentration Value	Free TFPI concentration value prior to the last dose administration after atleast 76 weeks is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.	Prior to the last dose administration after atleast 76 weeks
Secondary	Peak Thrombin Generation	Peak thrombin generation is the maximal concentration of thrombin formed at a given point in time. Peak thrombin generation prior to the last dose administration at 24 weeks is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.	Prior to the last dose administration at 24 weeks
Secondary	Peak Thrombin Generation	Peak thrombin generation is the maximal concentration of thrombin formed at a given point in time. Peak thrombin generation prior to the last dose administration after atleast 76 weeks is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.	Prior to the last dose administration after atleast 76 weeks
Secondary	Endogenous Thrombin Potential	Endogenous thrombin potential prior to the last dose administration at 24 weeks is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.	Prior to the last dose administration at 24 weeks
Secondary	Endogenous Thrombin Potential	Endogenous thrombin potential prior to the last dose administration after at least 76 weeks is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.	Prior to the last dose administration after atleast 76 weeks
Secondary	Thrombin Generation Velocity Index	Thrombin generation velocity index prior to the last dose administration at 24 weeks is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.	Prior to the last dose administration at 24 weeks
Secondary	Thrombin Generation Velocity Index	Thrombin generation velocity index prior to the last dose administration after at least 76 weeks is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.	Prior to the last dose administration after atleast 76 weeks