A Trial Evaluating Efficacy and Safety of Prophylactic Administration of Concizumab in Patients With Severe Haemophilia A Without Inhibitors

Haemophilia A Clinical Trial

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Official title:

A Multi-Centre Trial Evaluating Efficacy and Safety of Prophylactic Administration of Concizumab in Patients With Severe Haemophilia A Without Inhibitors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03196297
• Other study ID #: NN7415-4255
• Secondary ID: U1111-1179-38722
• Status: Completed
• Phase: Phase 2
• Start date: August 16, 2017
• Est. completion date: June 3, 2020

Study information

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

Clinical Trial Summary

This trial is conducted in Asia, Europe and the United States of America (USA). 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 patients with severe haemophilia A without inhibitors.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: June 3, 2020
• Est. primary completion date: June 22, 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 patients aged 18 years or older at the time of signing informed consent, diagnosed with severe haemophilia A (FVIII activity below 1%), based on medical records or results at screening Exclusion Criteria: - Known or suspected hypersensitivity to trial product(s) or related products - Known inherited or acquired bleeding disorder other than haemophilia A - Presence of inhibitors (neutralising antibodies) to Factor VIII (equal to or above 0.6 Bethesda Units) at screening measured by the Nijmegen method

Related Conditions & MeSH terms

• Haemophilia A
• Haemostasis
• Hemophilia A

Intervention

Drug:
• Concizumab
0.15 mg/kg (with potential stepwise dose administration to 0.25 mg/kg) administered daily s.c (subcutaneously, under the skin). Treatment duration is 24 weeks in the main phase, and 52 weeks in the extension phase
• Turoctocog alfa
Breakthrough bleeding episodes will be treated by the patients at home with turoctocog alfa at the discretion of the study doctor, who will also choose dose levels

Locations

Country	Name	City	State
France	Novo Nordisk Investigational Site	Brest
France	Novo Nordisk Investigational Site	Caen
France	Novo Nordisk Investigational Site	Nantes Cedex 1
Germany	Novo Nordisk Investigational Site	Bonn
Germany	Novo Nordisk Investigational Site	Homburg
Italy	Novo Nordisk Investigational Site	Milano
Italy	Novo Nordisk Investigational Site	Rome
Japan	Novo Nordisk Investigational Site	Aichi
Japan	Novo Nordisk Investigational Site	Nara
Japan	Novo Nordisk Investigational Site	Tokyo
Japan	Novo Nordisk Investigational Site	Tokyo
Spain	Novo Nordisk Investigational Site	Madrid
Spain	Novo Nordisk Investigational Site	Málaga
Spain	Novo Nordisk Investigational Site	Valencia
Sweden	Novo Nordisk Investigational Site	Malmö
Sweden	Novo Nordisk Investigational Site	Solna
Thailand	Novo Nordisk Investigational Site	Bangkok
Turkey	Novo Nordisk Investigational Site	Ankara
Turkey	Novo Nordisk Investigational Site	Bornova-IZMIR
Turkey	Novo Nordisk Investigational Site	Edirne
Turkey	Novo Nordisk Investigational Site	Istanbul
Ukraine	Novo Nordisk Investigational Site	Lviv
United Kingdom	Novo Nordisk Investigational Site	Belfast
United Kingdom	Novo Nordisk Investigational Site	Cambridge
United Kingdom	Novo Nordisk Investigational Site	London
United Kingdom	Novo Nordisk Investigational Site	London
United States	Novo Nordisk Investigational Site	Indianapolis	Indiana
United States	Novo Nordisk Investigational Site	Los Angeles	California
United States	Novo Nordisk Investigational Site	Nashville	Tennessee
United States	Novo Nordisk Investigational Site	Oklahoma City	Oklahoma
United States	Novo Nordisk Investigational Site	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  France,  Germany,  Italy,  Japan,  Spain,  Sweden,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Number of Bleeding Episodes During at Least 24 Weeks From Treatment Onset	The number of bleeding episodes that were treated during at least 24 weeks from treatment onset are presented. The data is presented while on last dose level when the bleed occurred.	During at least 24 weeks from treatment onset
Secondary	The Number of Bleeding Episodes During at Least 76 Weeks From Treatment Onset	The number of bleeding episodes that were treated during at least 76 weeks from treatment onset are presented. The data is presented while on last dose level when the bleed occurred.	During at least 76 weeks from treatment onset
Secondary	The Number of Spontaneous Bleeding Episodes During at Least 24 Weeks From Treatment Onset	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 are presented. The data is presented while on last dose level when the bleed occurred.	During at least 24 weeks from treatment onset
Secondary	The Number of Spontaneous Bleeding Episodes During at Least 76 Weeks From Treatment Onset	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 are presented. The data is presented while on last dose level when the bleed occurred.	During at least 76 weeks from treatment onset
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 dose level participants were on at the time of onset of the adverse 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 dose level participants were on at the time of onset of the adverse event.	During at least 76 weeks from treatment onset (week 0)
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. In the reported data, 'Yes' infers number of participants who showed positive anti-concizumab antibody tests whereas 'No' infers number of participants who showed negative anti-concizumab antibody tests.	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. In the reported data, 'Yes' infers number of participants who showed positive anti-concizumab antibody tests whereas 'No' infers number of participants who showed negative anti-concizumab antibody tests.	During at least 76 weeks from treatment onset (week 0)
Secondary	Change in Fibrinogen During 24 Weeks From Treatment Onset	Change in fibrinogen during 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 24 weeks from treatment onset (week 0)
Secondary	Change in Fibrinogen During at Least 76 Weeks From Treatment Onset	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 During 24 Weeks From Treatment Onset	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 24 weeks from treatment onset (week 0)
Secondary	Change in D-dimer During at Least 76 Weeks From Treatment Onset	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 + F2) During 24 Weeks From Treatment Onset	Change in F1 + F2 during 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 24 weeks from treatment onset (week 0)
Secondary	Change in Prothrombin Fragment 1 + 2 (F1 + F2) During at Least 76 Weeks From Treatment Onset	Change in F1 + F2 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) During 24 Weeks From Treatment Onset	Change in PT during 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 24 weeks from treatment onset (week 0)
Secondary	Change in Prothrombin Time (PT) During at Least 76 Weeks From Treatment Onset	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) During 24 Weeks From Treatment Onset	Change in APTT during 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 24 weeks from treatment onset (week 0)
Secondary	Change in Activated Partial Thromboplastin Time (APTT) During at Least 76 Weeks From Treatment Onset	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) During 24 Weeks From Treatment Onset	Change in AT during 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 24 weeks from treatment onset (week 0)
Secondary	Change in Anti-thrombin (AT) After at Least 76 Weeks From Treatment	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.	During at least 76 weeks from treatment onset (week 0)
Secondary	Concentration of Concizumab Prior to the Last Dose Administration at 24 Weeks	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 Prior to the Last Dose Administration After at Least 76 Weeks	Concentration of concizumab 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 at least 76 weeks
Secondary	Free Tissue Factor Pathway Inhibitor (TFPI) Concentration Value Prior to the Last Dose Administration at 24 Weeks	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 Prior to the Last Dose Administration After at Least 76 Weeks	Free TFPI concentration value 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 at least 76 weeks
Secondary	Peak Thrombin Generation Prior to the Last Dose Administration at 24 Weeks	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 Prior to the Last Dose Administration After at Least 76 Weeks	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 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 at least 76 weeks
Secondary	Endogenous Thrombin Potential Prior to the Last Dose Administration at 24 Weeks	The endogenous thrombin potential (ETP), defined as the amount of thrombin which can be generated after the in vitro activation of coagulation with tissue factor as trigger and phospholipids as platelet substitute. 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 Prior to the Last Dose Administration After at Least 76 Weeks	The endogenous thrombin potential (ETP), defined as the amount of thrombin which can be generated after the in vitro activation of coagulation with tissue factor as trigger and phospholipids as platelet substitute. 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 at least 76 weeks
Secondary	Thrombin Generation Velocity Index Prior to the Last Dose Administration at 24 Weeks	Thrombin generation velocity index represents the effective rate of thrombin generation between lag time and time to peak. 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 Prior to the Last Dose Administration After at Least 76 Weeks	Thrombin generation velocity index represents the effective rate of thrombin generation between lag time and time to peak. 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 at least 76 weeks