A Trial Evaluating Efficacy and Safety of Prophylactic Administration of Concizumab in Patients With Severe Haemophilia A Without Inhibitors (explorer™5)

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

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.

Study Overview

• Status: Completed
• Conditions: Haemophilia A; Haemostasis
• Intervention / Treatment: Drug: Concizumab; Drug: Turoctocog alfa

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Brest, France, 29609
    • Novo Nordisk Investigational Site
  • Caen, France, 14033
    • Novo Nordisk Investigational Site
  • Nantes Cedex 1, France, 44093
    • Novo Nordisk Investigational Site
• Germany
  • Bonn, Germany, 53127
    • Novo Nordisk Investigational Site
  • Homburg, Germany, 66421
    • Novo Nordisk Investigational Site
• Italy
  • Milano, Italy, 20124
    • Novo Nordisk Investigational Site
  • Rome, Italy, 00168
    • Novo Nordisk Investigational Site
• Japan
  • Aichi, Japan, 466-8560
    • Novo Nordisk Investigational Site
  • Nara, Japan, 634-8522
    • Novo Nordisk Investigational Site
  • Tokyo, Japan, 167-0035
    • Novo Nordisk Investigational Site
  • Tokyo, Japan, 160-0023
    • Novo Nordisk Investigational Site
• Spain
  • Madrid, Spain, 28046
    • Novo Nordisk Investigational Site
  • Málaga, Spain, 29010
    • Novo Nordisk Investigational Site
  • Valencia, Spain, 46026
    • Novo Nordisk Investigational Site
• Sweden
  • Malmö, Sweden, 205 02
    • Novo Nordisk Investigational Site
  • Solna, Sweden, 171 64
    • Novo Nordisk Investigational Site
• Thailand
  • Bangkok, Thailand, 10400
    • Novo Nordisk Investigational Site
• Turkey
  • Ankara, Turkey, 06100
    • Novo Nordisk Investigational Site
  • Bornova-IZMIR, Turkey, 35100
    • Novo Nordisk Investigational Site
  • Edirne, Turkey, 22030
    • Novo Nordisk Investigational Site
  • İstanbul, Turkey, 34098
    • Novo Nordisk Investigational Site
• Ukraine
  • Lviv, Ukraine, 79044
    • Novo Nordisk Investigational Site
• United Kingdom
  • Belfast, United Kingdom, BT9 7AB
    • Novo Nordisk Investigational Site
  • Cambridge, United Kingdom, CB2 0QQ
    • Novo Nordisk Investigational Site
  • London, United Kingdom, NW3 2QG
    • Novo Nordisk Investigational Site
  • London, United Kingdom, SE1 7EH
    • Novo Nordisk Investigational Site
• United States
  • California
    • Los Angeles, California, United States, 90027
      • Novo Nordisk Investigational Site
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Novo Nordisk Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Novo Nordisk Investigational Site
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Novo Nordisk Investigational Site
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Concizumab; Daily administration of concizumab to both on-demand and prophylaxis patients

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; Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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
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
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• Shapiro AD, Angchaisuksiri P, Astermark J, Benson G, Castaman G, Eichler H, Jimenez-Yuste V, Kavakli K, Matsushita T, Poulsen LH, Wheeler AP, Young G, Zupancic-Salek S, Oldenburg J, Chowdary P. Long-term efficacy and safety of subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors. Blood Adv. 2022 Jun 14;6(11):3422-3432. doi: 10.1182/bloodadvances.2021006403.
• Shapiro AD, Angchaisuksiri P, Astermark J, Benson G, Castaman G, Chowdary P, Eichler H, Jimenez-Yuste V, Kavakli K, Matsushita T, Poulsen LH, Wheeler AP, Young G, Zupancic-Salek S, Oldenburg J. Subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors: phase 2 trial results. Blood. 2019 Nov 28;134(22):1973-1982. doi: 10.1182/blood.2019001542.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 16, 2017
• Primary Completion (ACTUAL): June 22, 2018
• Study Completion (ACTUAL): June 3, 2020

Study Registration Dates

• First Submitted: June 20, 2017
• First Submitted That Met QC Criteria: June 20, 2017
• First Posted (ACTUAL): June 22, 2017

Study Record Updates

• Last Update Posted (ACTUAL): November 16, 2021
• Last Update Submitted That Met QC Criteria: November 15, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A
• Other Study ID Numbers: NN7415-4255; U1111-1179-3872 (OTHER: World Health Organization (WHO)); 2016-000614-29 (REGISTRY: EudraCT); JapicCTI-173682 (REGISTRY: JAPIC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No