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

Phase 2CompletedNCT03196284

Novo Nordisk A/S26 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Congenital Bleeding Disorder Haemophilia A With Inhibitors Haemophilia B With Inhibitors

Interventions

ConcizumabDRUG

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 alfaDRUG

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

Eligibility

Sex: MALEMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (22)

Novo Nordisk Investigational Site

Los Angeles, California, United States

Outcomes

Primary Outcomes

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.

Time frame: During at least 24 weeks from treatment onset (week 0)

Secondary Outcomes

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.

Time frame: During at least 76 weeks from treatment onset (week 0)

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.

Time frame: During at least 24 weeks from treatment onset (week 0)

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.

Time frame: During at least 76 weeks from treatment onset (week 0)

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.

Data from ClinicalTrials.gov

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Novo Nordisk Investigational Site

Indianapolis, Indiana, United States

Novo Nordisk Investigational Site

Iowa City, Iowa, United States

Novo Nordisk Investigational Site

Vienna, Austria

Novo Nordisk Investigational Site

Toronto, Ontario, Canada

Novo Nordisk Investigational Site

Zagreb, Croatia

Novo Nordisk Investigational Site

Århus N, Denmark

Novo Nordisk Investigational Site

Athens, Greece

Novo Nordisk Investigational Site

Tel Litwinsky, Israel

Novo Nordisk Investigational Site

Florence, Italy

...and 12 more locations

Time frame: During at least 24 weeks from treatment onset (week 0)

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.

Time frame: During at least 76 weeks from treatment onset (week 0)

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.

Time frame: Within 24 hours after eptacog alfa administration

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.

Time frame: During at least 24 weeks from treatment onset (week 0)

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.

Time frame: During at least 76 weeks from treatment onset (week 0)

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.

Time frame: During at least 24 weeks from treatment onset (week 0)

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.

Time frame: During at least 76 weeks from treatment onset (week 0)

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.

Time frame: During at least 24 weeks from treatment onset (week 0)

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.

Time frame: During at least 76 weeks from treatment onset (week 0)

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.

Time frame: During at least 24 weeks from treatment onset (week 0)

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.

Time frame: During at least 76 weeks from treatment onset (week 0)

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.

Time frame: During at least 24 weeks from treatment onset (week 0)

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.

Time frame: During at least 76 weeks from treatment onset (week 0)

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.

Time frame: During at least 24 weeks from treatment onset (week 0)

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.

Time frame: During at least 76 weeks from treatment onset (week 0)

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.

Time frame: During at least 24 weeks from treatment onset (week 0)

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.

Time frame: After at least 76 weeks from treatment onset (week 0)

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.

Time frame: Prior to the last dose administration at 24 weeks

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.

Time frame: Prior to the last dose administration after atleast 76 weeks

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.

Time frame: Prior to the last dose administration at 24 weeks

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.

Time frame: Prior to the last dose administration after atleast 76 weeks

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.

Time frame: Prior to the last dose administration at 24 weeks

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.

Time frame: Prior to the last dose administration after atleast 76 weeks

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.

Time frame: Prior to the last dose administration at 24 weeks

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.

Time frame: Prior to the last dose administration after atleast 76 weeks

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.

Time frame: Prior to the last dose administration at 24 weeks

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.

Time frame: Prior to the last dose administration after atleast 76 weeks