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

Sponsor

Novo Nordisk A/S (Industry)

Overall Status

Completed

CT.gov ID

NCT03196297

Collaborator

(none)

Enrollment

Locations

Arm

33.6

Actual Duration (Months)

1.2

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Haemostasis Haemophilia A	Drug: Concizumab Drug: Turoctocog alfa	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

36 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Aug 16, 2017

Actual Primary Completion Date :

Jun 22, 2018

Actual Study Completion Date :

Jun 3, 2020

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

The Number of Bleeding Episodes During at Least 24 Weeks From Treatment Onset [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.

Secondary Outcome Measures

The Number of Bleeding Episodes During at Least 76 Weeks From Treatment Onset [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.
The Number of Spontaneous Bleeding Episodes During at Least 24 Weeks From Treatment Onset [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.
The Number of Spontaneous Bleeding Episodes During at Least 76 Weeks From Treatment Onset [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.
Number of Treatment-emergent Adverse Events (TEAEs) During at Least 24 Weeks From Treatment Onset [During at least 24 weeks from treatment onset (week 0)]
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.
Number of Treatment-emergent Adverse Events (TEAEs) During at Least 76 Weeks From Treatment Onset [During at least 76 weeks from treatment onset (week 0)]
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.
Occurrence of Anti-concizumab Antibodies During at Least 24 Weeks From Treatment Onset [During at least 24 weeks from treatment onset (week 0)]
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.
Occurrence of Anti-concizumab Antibodies During at Least 76 Weeks From Treatment Onset [During at least 76 weeks from treatment onset (week 0)]
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.
Change in Fibrinogen During 24 Weeks From Treatment Onset [During 24 weeks from treatment onset (week 0)]
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.
Change in Fibrinogen During at Least 76 Weeks From Treatment Onset [During at least 76 weeks from treatment onset (week 0)]
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.
Change in D-dimer During 24 Weeks From Treatment Onset [During 24 weeks from treatment onset (week 0)]
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.
Change in D-dimer During at Least 76 Weeks From Treatment Onset [During at least 76 weeks from treatment onset (week 0)]
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.
Change in Prothrombin Fragment 1 + 2 (F1 + F2) During 24 Weeks From Treatment Onset [During 24 weeks from treatment onset (week 0)]
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.
Change in Prothrombin Fragment 1 + 2 (F1 + F2) During at Least 76 Weeks From Treatment Onset [During at least 76 weeks from treatment onset (week 0)]
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.
Change in Prothrombin Time (PT) During 24 Weeks From Treatment Onset [During 24 weeks from treatment onset (week 0)]
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.
Change in Prothrombin Time (PT) During at Least 76 Weeks From Treatment Onset [During at least 76 weeks from treatment onset (week 0)]
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.
Change in Activated Partial Thromboplastin Time (APTT) During 24 Weeks From Treatment Onset [During 24 weeks from treatment onset (week 0)]
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.
Change in Activated Partial Thromboplastin Time (APTT) During at Least 76 Weeks From Treatment Onset [During at least 76 weeks from treatment onset (week 0)]
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.
Change in Anti-thrombin (AT) During 24 Weeks From Treatment Onset [During 24 weeks from treatment onset (week 0)]
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.
Change in Anti-thrombin (AT) After at Least 76 Weeks From Treatment [During at least 76 weeks from treatment onset (week 0)]
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.
Concentration of Concizumab Prior to the Last Dose Administration at 24 Weeks [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.
Concentration of Concizumab Prior to the Last Dose Administration After at Least 76 Weeks [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.
Free Tissue Factor Pathway Inhibitor (TFPI) Concentration Value Prior to the Last Dose Administration at 24 Weeks [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.
Free Tissue Factor Pathway Inhibitor (TFPI) Concentration Value Prior to the Last Dose Administration After at Least 76 Weeks [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.
Peak Thrombin Generation Prior to the Last Dose Administration at 24 Weeks [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.
Peak Thrombin Generation Prior to the Last Dose Administration After at Least 76 Weeks [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.
Endogenous Thrombin Potential Prior to the Last Dose Administration at 24 Weeks [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.
Endogenous Thrombin Potential Prior to the Last Dose Administration After at Least 76 Weeks [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.
Thrombin Generation Velocity Index Prior to the Last Dose Administration at 24 Weeks [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.
Thrombin Generation Velocity Index Prior to the Last Dose Administration After at Least 76 Weeks [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Los Angeles	California	United States	90027
2	Novo Nordisk Investigational Site	Indianapolis	Indiana	United States	46260
3	Novo Nordisk Investigational Site	Oklahoma City	Oklahoma	United States	73104
4	Novo Nordisk Investigational Site	Nashville	Tennessee	United States	37232
5	Novo Nordisk Investigational Site	Salt Lake City	Utah	United States	84113
6	Novo Nordisk Investigational Site	Brest		France	29609
7	Novo Nordisk Investigational Site	Caen		France	14033
8	Novo Nordisk Investigational Site	Nantes Cedex 1		France	44093
9	Novo Nordisk Investigational Site	Bonn		Germany	53127
10	Novo Nordisk Investigational Site	Homburg		Germany	66421
11	Novo Nordisk Investigational Site	Milano		Italy	20124
12	Novo Nordisk Investigational Site	Rome		Italy	00168
13	Novo Nordisk Investigational Site	Aichi		Japan	466-8560
14	Novo Nordisk Investigational Site	Nara		Japan	634-8522
15	Novo Nordisk Investigational Site	Tokyo		Japan	160-0023
16	Novo Nordisk Investigational Site	Tokyo		Japan	167-0035
17	Novo Nordisk Investigational Site	Madrid		Spain	28046
18	Novo Nordisk Investigational Site	Málaga		Spain	29010
19	Novo Nordisk Investigational Site	Valencia		Spain	46026
20	Novo Nordisk Investigational Site	Malmö		Sweden	205 02
21	Novo Nordisk Investigational Site	Solna		Sweden	171 64
22	Novo Nordisk Investigational Site	Bangkok		Thailand	10400
23	Novo Nordisk Investigational Site	Ankara		Turkey	06100
24	Novo Nordisk Investigational Site	Bornova-IZMIR		Turkey	35100
25	Novo Nordisk Investigational Site	Edirne		Turkey	22030
26	Novo Nordisk Investigational Site	İstanbul		Turkey	34098
27	Novo Nordisk Investigational Site	Lviv		Ukraine	79044
28	Novo Nordisk Investigational Site	Belfast		United Kingdom	BT9 7AB
29	Novo Nordisk Investigational Site	Cambridge		United Kingdom	CB2 0QQ
30	Novo Nordisk Investigational Site	London		United Kingdom	NW3 2QG
31	Novo Nordisk Investigational Site	London		United Kingdom	SE1 7EH

Sponsors and Collaborators

Novo Nordisk A/S

Investigators

None specified.

Study Documents (Full-Text)

More Information

Publications

None provided.

Responsible Party:

Novo Nordisk A/S

ClinicalTrials.gov Identifier:

NCT03196297

Other Study ID Numbers:

NN7415-4255
U1111-1179-3872
2016-000614-29
JapicCTI-173682

First Posted:

Jun 22, 2017

Last Update Posted:

Nov 16, 2021

Last Verified:

Nov 1, 2021

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:

Additional relevant MeSH terms:

Hemophilia A

Study Results

Participant Flow

Recruitment Details	The trial was conducted at 26 sites in 11 countries as follows: France (3), Germany (2), Italy (1), Japan (3), Spain (3), Sweden (2), Thailand (1), Turkey (3), the United Kingdom (4), Ukraine (1) and the United States (3). In addition to these sites, 5 sites were approved by the IRB/IEC and/or local health authority but did not screen or assign any participants to treatment.
Pre-assignment Detail	The trial consisted of two treatment periods: main part which lasted at least 24 weeks for all participants in the trial and an extension part which was up to 102 weeks.

Arm/Group Title	Concizumab
Arm/Group Description	Participants received subcutaneous (s.c.) injection of concizumab once daily for up to 126 weeks (at least 24 weeks main part + 52-102 weeks extension part). The initial dose was 0.15 milligrams per kilogram (mg/kg) and then the dose was escalated to 0.20 and 0.25 mg/kg based on the number of spontaneous bleeding episodes. Participants continued the extension phase at the same dose of concizumab once daily they have reached at the end of main part for 52-102 weeks with the potential dose escalation based on the number of spontaneous bleeding episodes.
Period Title: Main Period
STARTED	36
Full Analysis Set (FAS)	36
Subject Analysis Set (SAS)	36
COMPLETED	32
NOT COMPLETED	4
Period Title: Main Period
STARTED	32
FAS	32
SAS	32
COMPLETED	29
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Concizumab
Arm/Group Description	Participants were to receive subcutaneous (s.c.) injection of concizumab once daily for up to 126 weeks (24 weeks main part + 52-102 weeks extension part). The initial dose was 0.15 milligrams per kilogram (mg/kg) and then the dose was escalated to 0.20 and 0.25 mg/kg based on the number of spontaneous bleeding episodes. Participants continued the extension phase at the same dose of concizumab once daily they have reached at the end of main part for 52-102 weeks with the potential dose escalation based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.
Overall Participants	36
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	36.9 (12.9)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	36 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 8.3%
Not Hispanic or Latino	30 83.3%
Unknown or Not Reported	3 8.3%
Race/Ethnicity, Customized (Count of Participants)
Asian	8 22.2%
White	24 66.7%
Other	1 2.8%
Not applicable	3 8.3%

Outcome Measures

1. Primary Outcome

Title	The Number of Bleeding Episodes During at Least 24 Weeks From Treatment Onset
Description	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.
Time Frame	During at least 24 weeks from treatment onset

Outcome Measure Data

Analysis Population Description
The FAS included all participants who took al least one dose of the study drug.

Arm/Group Title	Concizumab 0.15 mg/kg- Main Part	Concizumab 0.20 mg/kg- Main Part	Concizumab 0.25 mg/kg- Main Part
Arm/Group Description	Participants received s.c. injection of 0.15 mg/kg concizumab once daily for 24 weeks. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants received s.c. injection of concizumab once daily for 24 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants received s.c. injection of concizumab once daily for 24 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 and 0.25 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.
Measure Participants	21	7	8
Number [Episodes]	43	13	14

2. Secondary Outcome

Title	The Number of Bleeding Episodes During at Least 76 Weeks From Treatment Onset
Description	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.
Time Frame	During at least 76 weeks from treatment onset

Outcome Measure Data

Analysis Population Description
The FAS included all participants who took al least one dose of the study drug.

Arm/Group Title	Concizumab 0.15 mg/kg	Concizumab 0.20 mg/kg	Concizumab 0.25 mg/kg
Arm/Group Description	Participants were to receive s.c. injection of 0.15 mg/kg of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks with the potential dose escalation based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants were to receive s.c. injection of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants were to receive s.c. injection of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.25 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.
Measure Participants	15	10	10
Number [Episodes]	67	42	123

3. Secondary Outcome

Title	The Number of Spontaneous Bleeding Episodes During at Least 24 Weeks From Treatment Onset
Description	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.
Time Frame	During at least 24 weeks from treatment onset

Outcome Measure Data

Analysis Population Description
The FAS included all participants who took al least one dose of the study drug.

Arm/Group Title	Concizumab 0.15 mg/kg- Main Part	Concizumab 0.20 mg/kg- Main Part	Concizumab 0.25 mg/kg- Main Part
Arm/Group Description	Participants received s.c. injection of 0.15 mg/kg concizumab once daily for 24 weeks. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants received s.c. injection of concizumab once daily for 24 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants received s.c. injection of concizumab once daily for 24 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 and 0.25 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.
Measure Participants	21	7	8
Number [Episodes]	16	8	2

4. Secondary Outcome

Title	The Number of Spontaneous Bleeding Episodes During at Least 76 Weeks From Treatment Onset
Description	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.
Time Frame	During at least 76 weeks from treatment onset

Outcome Measure Data

Analysis Population Description
The FAS included all participants who took al least one dose of the study drug.

Arm/Group Title	Concizumab 0.15 mg/kg	Concizumab 0.20 mg/kg	Concizumab 0.25 mg/kg
Arm/Group Description	Participants were to receive s.c. injection of 0.15 mg/kg of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks with the potential dose escalation based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants were to receive s.c. injection of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants were to receive s.c. injection of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.25 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.
Measure Participants	15	10	10
Number [Episodes]	39	15	29

5. Secondary Outcome

Title	Number of Treatment-emergent Adverse Events (TEAEs) During at Least 24 Weeks From Treatment Onset
Description	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.
Time Frame	During at least 24 weeks from treatment onset (week 0)

Outcome Measure Data

Analysis Population Description
The SAS included all participants who took al least one dose of the study drug.

Arm/Group Title	Concizumab 0.15 mg/kg- Main Part	Concizumab 0.20 mg/kg- Main Part	Concizumab 0.25 mg/kg- Main Part
Arm/Group Description	Participants received s.c. injection of 0.15 mg/kg concizumab once daily for 24 weeks. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants received s.c. injection of concizumab once daily for 24 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants received s.c. injection of concizumab once daily for 24 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 and 0.25 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.
Measure Participants	36	15	8
Number [Events]	105	16	9

6. Secondary Outcome

Title	Number of Treatment-emergent Adverse Events (TEAEs) During at Least 76 Weeks From Treatment Onset
Description	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.
Time Frame	During at least 76 weeks from treatment onset (week 0)

Outcome Measure Data

Analysis Population Description
The SAS included all participants who took al least one dose of the study drug.

Arm/Group Title	Concizumab 0.15 mg/kg	Concizumab 0.20 mg/kg	Concizumab 0.25 mg/kg
Arm/Group Description	Participants were to receive s.c. injection of 0.15 mg/kg of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks with the potential dose escalation based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants were to receive s.c. injection of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants were to receive s.c. injection of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.25 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.
Measure Participants	36	21	11
Number [Events]	201	53	44

7. Secondary Outcome

Title	Occurrence of Anti-concizumab Antibodies During at Least 24 Weeks From Treatment Onset
Description	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.
Time Frame	During at least 24 weeks from treatment onset (week 0)

Outcome Measure Data

Analysis Population Description
The FAS included all participants who took al least one dose of the study drug.

Arm/Group Title	Concizumab - Main Part
Arm/Group Description	Participants were to receive subcutaneous (s.c.) injection of concizumab once daily for 24 weeks. The initial dose was 0.15 milligrams per kilogram (mg/kg) and then the dose was escalated to 0.20 and 0.25 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.
Measure Participants	36
Yes	3 8.3%
No	33 91.7%

8. Secondary Outcome

Title	Occurrence of Anti-concizumab Antibodies During at Least 76 Weeks From Treatment Onset
Description	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.
Time Frame	During at least 76 weeks from treatment onset (week 0)

Outcome Measure Data

Analysis Population Description
The FAS included all participants who took al least one dose of the study drug.

Arm/Group Title	Concizumab
Arm/Group Description	Participants who completed main part treatment were continued the same dose regimen for concizumab once daily for 52-102 weeks with the potential dose escalation based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.
Measure Participants	36
Yes	9 25%
No	27 75%

9. Secondary Outcome

Title	Change in Fibrinogen During 24 Weeks From Treatment Onset
Description	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.
Time Frame	During 24 weeks from treatment onset (week 0)

Outcome Measure Data

Analysis Population Description
The SAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.

Arm/Group Title	Concizumab 0.15 mg/kg- Main Part	Concizumab 0.20 mg/kg- Main Part	Concizumab 0.25 mg/kg- Main Part
Arm/Group Description	Participants received s.c. injection of 0.15 mg/kg concizumab once daily for 24 weeks. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants received s.c. injection of concizumab once daily for 24 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants received s.c. injection of concizumab once daily for 24 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 and 0.25 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.
Measure Participants	19	7	8
Mean (Standard Deviation) [gram per litre (g/L)]	-0.08 (0.61)	-0.19 (0.47)	-0.27 (0.29)

10. Secondary Outcome

Title	Change in Fibrinogen During at Least 76 Weeks From Treatment Onset
Description	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)

Outcome Measure Data

Analysis Population Description
The SAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.

Arm/Group Title	Concizumab 0.15 mg/kg	Concizumab 0.20 mg/kg	Concizumab 0.25 mg/kg
Arm/Group Description	Participants were to receive s.c. injection of 0.15 mg/kg of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks with the potential dose escalation based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants were to receive s.c. injection of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants were to receive s.c. injection of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.25 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.
Measure Participants	13	10	7
Mean (Standard Deviation) [gram per litre (g/L)]	-0.05 (0.39)	-0.35 (0.56)	-0.23 (0.63)

11. Secondary Outcome

Title	Change in D-dimer During 24 Weeks From Treatment Onset
Description	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 24 weeks from treatment onset (week 0)

Outcome Measure Data

Analysis Population Description
The SAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.

Arm/Group Title	Concizumab 0.15 mg/kg- Main Part	Concizumab 0.20 mg/kg- Main Part	Concizumab 0.25 mg/kg- Main Part
Arm/Group Description	Participants received s.c. injection of 0.15 mg/kg concizumab once daily for 24 weeks. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants received s.c. injection of concizumab once daily for 24 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants received s.c. injection of concizumab once daily for 24 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 and 0.25 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.
Measure Participants	19	7	8
Mean (Standard Deviation) [Nanograms per milliliter (ng/mL)]	184.5 (404.5)	272.9 (684.4)	703.8 (693.6)

12. Secondary Outcome

Title	Change in D-dimer During at Least 76 Weeks From Treatment Onset
Description	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)

Outcome Measure Data

Analysis Population Description
The SAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.

Arm/Group Title	Concizumab 0.15 mg/kg	Concizumab 0.20 mg/kg	Concizumab 0.25 mg/kg
Arm/Group Description	Participants were to receive s.c. injection of 0.15 mg/kg of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks with the potential dose escalation based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants were to receive s.c. injection of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants were to receive s.c. injection of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.25 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.
Measure Participants	14	9	7
Mean (Standard Deviation) [Nanograms per milliliter (ng/mL)]	265.4 (405.3)	506.7 (369.9)	1109.3 (818.5)

13. Secondary Outcome

Title	Change in Prothrombin Fragment 1 + 2 (F1 + F2) During 24 Weeks From Treatment Onset
Description	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.
Time Frame	During 24 weeks from treatment onset (week 0)

Outcome Measure Data

Analysis Population Description
The SAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.

Arm/Group Title	Concizumab 0.15 mg/kg- Main Part	Concizumab 0.20 mg/kg- Main Part	Concizumab 0.25 mg/kg- Main Part
Arm/Group Description	Participants received s.c. injection of 0.15 mg/kg concizumab once daily for 24 weeks. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants received s.c. injection of concizumab once daily for 24 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants received s.c. injection of concizumab once daily for 24 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 and 0.25 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.
Measure Participants	19	7	8
Mean (Standard Deviation) [Picomoles per liter (pmol/L)]	134 (156)	257 (524)	580 (741)

14. Secondary Outcome

Title	Change in Prothrombin Fragment 1 + 2 (F1 + F2) During at Least 76 Weeks From Treatment Onset
Description	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.
Time Frame	During at least 76 weeks from treatment onset (week 0)

Outcome Measure Data

Analysis Population Description
The SAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.

Arm/Group Title	Concizumab 0.15 mg/kg	Concizumab 0.20 mg/kg	Concizumab 0.25 mg/kg
Arm/Group Description	Participants were to receive s.c. injection of 0.15 mg/kg of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks with the potential dose escalation based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants were to receive s.c. injection of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants were to receive s.c. injection of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.25 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.
Measure Participants	14	9	7
Mean (Standard Deviation) [pmol/L]	128 (183)	211 (207)	889 (423)

15. Secondary Outcome

Title	Change in Prothrombin Time (PT) During 24 Weeks From Treatment Onset
Description	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.
Time Frame	During 24 weeks from treatment onset (week 0)

Outcome Measure Data

Analysis Population Description
The SAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.

Arm/Group Title	Concizumab 0.15 mg/kg- Main Part	Concizumab 0.20 mg/kg- Main Part	Concizumab 0.25 mg/kg- Main Part
Arm/Group Description	Participants received s.c. injection of 0.15 mg/kg concizumab once daily for 24 weeks. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants received s.c. injection of concizumab once daily for 24 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants received s.c. injection of concizumab once daily for 24 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 and 0.25 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.
Measure Participants	19	7	8
Mean (Standard Deviation) [Seconds (sec)]	-0.0 (0.4)	-0.3 (0.9)	0.3 (0.7)

16. Secondary Outcome

Title	Change in Prothrombin Time (PT) During at Least 76 Weeks From Treatment Onset
Description	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)

Outcome Measure Data

Analysis Population Description
The SAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.

Arm/Group Title	Concizumab 0.15 mg/kg	Concizumab 0.20 mg/kg	Concizumab 0.25 mg/kg
Arm/Group Description	Participants were to receive s.c. injection of 0.15 mg/kg of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks with the potential dose escalation based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants were to receive s.c. injection of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants were to receive s.c. injection of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.25 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.
Measure Participants	14	9	7
Mean (Standard Deviation) [sec]	0.0 (0.4)	0.8 (2.7)	0.4 (0.4)

17. Secondary Outcome

Title	Change in Activated Partial Thromboplastin Time (APTT) During 24 Weeks From Treatment Onset
Description	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.
Time Frame	During 24 weeks from treatment onset (week 0)

Outcome Measure Data

Analysis Population Description
The SAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.

Arm/Group Title	Concizumab 0.15 mg/kg- Main Part	Concizumab 0.20 mg/kg- Main Part	Concizumab 0.25 mg/kg- Main Part
Arm/Group Description	Participants received s.c. injection of 0.15 mg/kg concizumab once daily for 24 weeks. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants received s.c. injection of concizumab once daily for 24 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants received s.c. injection of concizumab once daily for 24 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 and 0.25 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.
Measure Participants	19	7	8
Mean (Standard Deviation) [sec]	1.5 (10.2)	3.1 (6.1)	6.5 (6.9)

18. Secondary Outcome

Title	Change in Activated Partial Thromboplastin Time (APTT) During at Least 76 Weeks From Treatment Onset
Description	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)

Outcome Measure Data

Analysis Population Description
The SAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.

Arm/Group Title	Concizumab 0.15 mg/kg	Concizumab 0.20 mg/kg	Concizumab 0.25 mg/kg
Arm/Group Description	Participants were to receive s.c. injection of 0.15 mg/kg of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks with the potential dose escalation based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants were to receive s.c. injection of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants were to receive s.c. injection of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.25 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.
Measure Participants	14	9	7
Mean (Standard Deviation) [sec]	3.1 (4.3)	9.2 (8.8)	2.1 (9.4)

19. Secondary Outcome

Title	Change in Anti-thrombin (AT) During 24 Weeks From Treatment Onset
Description	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.
Time Frame	During 24 weeks from treatment onset (week 0)

Outcome Measure Data

Analysis Population Description
The SAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.

Arm/Group Title	Concizumab 0.15 mg/kg- Main Part	Concizumab 0.20 mg/kg- Main Part	Concizumab 0.25 mg/kg- Main Part
Arm/Group Description	Participants received s.c. injection of 0.15 mg/kg concizumab once daily for 24 weeks. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants received s.c. injection of concizumab once daily for 24 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants received s.c. injection of concizumab once daily for 24 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 and 0.25 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.
Measure Participants	19	7	8
Mean (Standard Deviation) [Percentage point]	7 (13)	17 (31)	7 (18)

20. Secondary Outcome

Title	Change in Anti-thrombin (AT) After at Least 76 Weeks From Treatment
Description	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	During at least 76 weeks from treatment onset (week 0)

Outcome Measure Data

Analysis Population Description
The SAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.

Arm/Group Title	Concizumab 0.15 mg/kg	Concizumab 0.20 mg/kg	Concizumab 0.25 mg/kg
Arm/Group Description	Participants were to receive s.c. injection of 0.15 mg/kg of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks with the potential dose escalation based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants were to receive s.c. injection of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants were to receive s.c. injection of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.25 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.
Measure Participants	14	9	7
Mean (Standard Deviation) [second]	0 (12)	11 (23)	15 (25)

21. Secondary Outcome

Title	Concentration of Concizumab Prior to the Last Dose Administration at 24 Weeks
Description	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

Outcome Measure Data

Analysis Population Description
The FAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.

Arm/Group Title	Concizumab 0.15 mg/kg- Main Part	Concizumab 0.20 mg/kg- Main Part	Concizumab 0.25 mg/kg- Main Part
Arm/Group Description	Participants received s.c. injection of 0.15 mg/kg concizumab once daily for 24 weeks. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants received s.c. injection of concizumab once daily for 24 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants received s.c. injection of concizumab once daily for 24 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 and 0.25 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.
Measure Participants	18	4	6
Mean (Standard Deviation) [ng/mL]	195.2 (147.0)	374.4 (644.0)	2640.8 (4085.6)

22. Secondary Outcome

Title	Concentration of Concizumab Prior to the Last Dose Administration After at Least 76 Weeks
Description	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.
Time Frame	Prior to the last dose administration after at least 76 weeks

Outcome Measure Data

Analysis Population Description
The FAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.

Arm/Group Title	Concizumab 0.15 mg/kg	Concizumab 0.20 mg/kg	Concizumab 0.25 mg/kg
Arm/Group Description	Participants were to receive s.c. injection of 0.15 mg/kg of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks with the potential dose escalation based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants were to receive s.c. injection of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants were to receive s.c. injection of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.25 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.
Measure Participants	13	10	7
Mean (Standard Deviation) [ng/mL]	195.1 (161.7)	392.3 (427.9)	4015.1 (2902.0)

23. Secondary Outcome

Title	Free Tissue Factor Pathway Inhibitor (TFPI) Concentration Value Prior to the Last Dose Administration at 24 Weeks
Description	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

Outcome Measure Data

Analysis Population Description
The FAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.

Arm/Group Title	Concizumab 0.15 mg/kg- Main Part	Concizumab 0.20 mg/kg- Main Part	Concizumab 0.25 mg/kg- Main Part
Arm/Group Description	Participants received s.c. injection of 0.15 mg/kg concizumab once daily for 24 weeks. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants received s.c. injection of concizumab once daily for 24 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants received s.c. injection of concizumab once daily for 24 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 and 0.25 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.
Measure Participants	18	4	6
Mean (Standard Deviation) [ng/mL]	30.1 (15.6)	64.4 (35.3)	12.4 (2.2)

24. Secondary Outcome

Title	Free Tissue Factor Pathway Inhibitor (TFPI) Concentration Value Prior to the Last Dose Administration After at Least 76 Weeks
Description	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.
Time Frame	Prior to the last dose administration after at least 76 weeks

Outcome Measure Data

Analysis Population Description
The FAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.

Arm/Group Title	Concizumab 0.15 mg/kg	Concizumab 0.20 mg/kg	Concizumab 0.25 mg/kg
Arm/Group Description	Participants were to receive s.c. injection of 0.15 mg/kg of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks with the potential dose escalation based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants were to receive s.c. injection of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants were to receive s.c. injection of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.25 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.
Measure Participants	13	10	7
Mean (Standard Deviation) [ng/mL]	26.9 (17.1)	36.1 (33.1)	10.1 (5.7)

25. Secondary Outcome

Title	Peak Thrombin Generation Prior to the Last Dose Administration at 24 Weeks
Description	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

Outcome Measure Data

Analysis Population Description
The FAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.

Arm/Group Title	Concizumab 0.15 mg/kg- Main Part	Concizumab 0.20 mg/kg- Main Part	Concizumab 0.25 mg/kg- Main Part
Arm/Group Description	Participants received s.c. injection of 0.15 mg/kg concizumab once daily for 24 weeks. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants received s.c. injection of concizumab once daily for 24 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants received s.c. injection of concizumab once daily for 24 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 and 0.25 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.
Measure Participants	18	4	5
Mean (Standard Deviation) [Nanomoles per liter (nmol/L)]	88.6 (34.5)	67.5 (35.0)	83.4 (10.6)

26. Secondary Outcome

Title	Peak Thrombin Generation Prior to the Last Dose Administration After at Least 76 Weeks
Description	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.
Time Frame	Prior to the last dose administration after at least 76 weeks

Outcome Measure Data

Analysis Population Description
The FAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.

Arm/Group Title	Concizumab 0.15 mg/kg	Concizumab 0.20 mg/kg	Concizumab 0.25 mg/kg
Arm/Group Description	Participants were to receive s.c. injection of 0.15 mg/kg of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks with the potential dose escalation based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants were to receive s.c. injection of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants were to receive s.c. injection of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.25 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.
Measure Participants	13	10	7
Mean (Standard Deviation) [nmol/L]	90.8 (45.2)	99.1 (36.2)	111.6 (63.5)

27. Secondary Outcome

Title	Endogenous Thrombin Potential Prior to the Last Dose Administration at 24 Weeks
Description	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.
Time Frame	Prior to the last dose administration at 24 weeks

Outcome Measure Data

Analysis Population Description
The FAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.

Arm/Group Title	Concizumab 0.15 mg/kg- Main Part	Concizumab 0.20 mg/kg- Main Part	Concizumab 0.25 mg/kg- Main Part
Arm/Group Description	Participants received s.c. injection of 0.15 mg/kg concizumab once daily for 24 weeks. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants received s.c. injection of concizumab once daily for 24 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants received s.c. injection of concizumab once daily for 24 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 and 0.25 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.
Measure Participants	18	4	5
Mean (Standard Deviation) [Nanomolarminute (nMmin)]	1229.1 (340.6)	965.3 (362.0)	1176.0 (278.8)

28. Secondary Outcome

Title	Endogenous Thrombin Potential Prior to the Last Dose Administration After at Least 76 Weeks
Description	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.
Time Frame	Prior to the last dose administration after at least 76 weeks

Outcome Measure Data

Analysis Population Description
The FAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.

Arm/Group Title	Concizumab 0.15 mg/kg	Concizumab 0.20 mg/kg	Concizumab 0.25 mg/kg
Arm/Group Description	Participants were to receive s.c. injection of 0.15 mg/kg of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks with the potential dose escalation based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants were to receive s.c. injection of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants were to receive s.c. injection of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.25 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.
Measure Participants	13	10	7
Mean (Standard Deviation) [nM*min]	1253.0 (507.3)	1352.6 (349.5)	1233.4 (267.9)

29. Secondary Outcome

Title	Thrombin Generation Velocity Index Prior to the Last Dose Administration at 24 Weeks
Description	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.
Time Frame	Prior to the last dose administration at 24 weeks

Outcome Measure Data

Analysis Population Description
The FAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.

Arm/Group Title	Concizumab 0.15 mg/kg- Main Part	Concizumab 0.20 mg/kg- Main Part	Concizumab 0.25 mg/kg- Main Part
Arm/Group Description	Participants received s.c. injection of 0.15 mg/kg concizumab once daily for 24 weeks. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants received s.c. injection of concizumab once daily for 24 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants received s.c. injection of concizumab once daily for 24 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 and 0.25 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.
Measure Participants	18	4	5
Mean (Standard Deviation) [nM/min]	9.3 (4.8)	7.0 (5.0)	8.2 (1.6)

30. Secondary Outcome

Title	Thrombin Generation Velocity Index Prior to the Last Dose Administration After at Least 76 Weeks
Description	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.
Time Frame	Prior to the last dose administration after at least 76 weeks

Outcome Measure Data

Analysis Population Description
The FAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.

Arm/Group Title	Concizumab 0.15 mg/kg	Concizumab 0.20 mg/kg	Concizumab 0.25 mg/kg
Arm/Group Description	Participants were to receive s.c. injection of 0.15 mg/kg of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks with the potential dose escalation based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants were to receive s.c. injection of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.	Participants were to receive s.c. injection of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.25 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.
Measure Participants	13	10	7
Mean (Standard Deviation) [Nano molar/min (nM/min)]	10.3 (6.4)	10.5 (4.8)	16.0 (17.1)

Adverse Events

	Concizumab 0.15 mg/kg - Main Part		Concizumab 0.20 mg/kg - Main Part		Concizumab 0.25 mg/kg - Main Part		Concizumab 0.15 mg/kg - Extension Part		Concizumab 0.20 mg/kg - Extension Part		Concizumab 0.25 mg/kg - Extension Part
Time Frame	From start of study drug administration (week 0) up to 134 weeks
Adverse Event Reporting Description	Results are based on the safety analysis set which included all dosed participants. All presented adverse events are treatment emergent adverse events (TEAEs). TEAE was defined as an event that had onset from the first exposure to treatment until the last visit in the trial. The data is presented per dose level participants were on at the time of onset of the adverse event. MedDRA version 21.0 is used for the main phase and MedDRA version 22.1 is used for the extension phase.

Arm/Group Title	Concizumab 0.15 mg/kg - Main Part		Concizumab 0.20 mg/kg - Main Part		Concizumab 0.25 mg/kg - Main Part		Concizumab 0.15 mg/kg - Extension Part		Concizumab 0.20 mg/kg - Extension Part		Concizumab 0.25 mg/kg - Extension Part
Arm/Group Description	Participants received s.c. injection of 0.15 mg/kg concizumab once daily for 24 weeks. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.		Participants received s.c. injection of concizumab once daily for 24 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.		Participants received s.c. injection of concizumab once daily for 24 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 and 0.25 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.		Participants were to receive s.c. injection of 0.15 mg/kg of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks with the potential dose escalation based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.		Participants were to receive s.c. injection of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.20 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.		Participants were to receive s.c. injection of concizumab once daily. Participants who completed the main part (24 weeks) of the study were continued the same dose regimen for concizumab once daily for 52-102 weeks. The initial dose was 0.15 mg/kg which was then escalated to 0.25 mg/kg based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/36 (0%)		0/15 (0%)		0/8 (0%)		0/19 (0%)		0/14 (0%)		0/10 (0%)
Serious Adverse Events
	Concizumab 0.15 mg/kg - Main Part		Concizumab 0.20 mg/kg - Main Part		Concizumab 0.25 mg/kg - Main Part		Concizumab 0.15 mg/kg - Extension Part		Concizumab 0.20 mg/kg - Extension Part		Concizumab 0.25 mg/kg - Extension Part
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/36 (0%)		0/15 (0%)		0/8 (0%)		2/19 (10.5%)		1/14 (7.1%)		2/10 (20%)
Gastrointestinal disorders
Gastrointestinal haemorrhage	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	0/19 (0%)	0	0/14 (0%)	0	1/10 (10%)	1
Infections and infestations
Atypical pneumonia	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	0/19 (0%)	0	0/14 (0%)	0	1/10 (10%)	1
Gastrointestinal infection	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
Injury, poisoning and procedural complications
Ligament sprain	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	0/19 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pharyngeal haemorrhage	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
Other (Not Including Serious) Adverse Events
	Concizumab 0.15 mg/kg - Main Part		Concizumab 0.20 mg/kg - Main Part		Concizumab 0.25 mg/kg - Main Part		Concizumab 0.15 mg/kg - Extension Part		Concizumab 0.20 mg/kg - Extension Part		Concizumab 0.25 mg/kg - Extension Part
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/36 (72.2%)		7/15 (46.7%)		3/8 (37.5%)		16/19 (84.2%)		9/14 (64.3%)		7/10 (70%)
Blood and lymphatic system disorders
Thrombocytopenia	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	0/19 (0%)	0	0/14 (0%)	0	1/10 (10%)	1
Cardiac disorders
Palpitations	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
Eye disorders
Pinguecula	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
Retinal detachment	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
Gastrointestinal disorders
Abdominal pain	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
Abdominal pain lower	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
Anal fistula	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	0/19 (0%)	0	0/14 (0%)	0	1/10 (10%)	1
Chronic gastritis	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	2/19 (10.5%)	2	0/14 (0%)	0	0/10 (0%)	0
Dental caries	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	1/14 (7.1%)	4	1/10 (10%)	1
Diarrhoea	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
Gastric polyps	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
Lip discolouration	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	0/19 (0%)	0	0/14 (0%)	0	1/10 (10%)	1
Mallory-Weiss syndrome	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
Toothache	0/36 (0%)	0	1/15 (6.7%)	1	0/8 (0%)	0	0/19 (0%)	0	0/14 (0%)	0	0/10 (0%)	0
Vomiting	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
General disorders
Exercise tolerance decreased	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
Granuloma	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
Influenza like illness	2/36 (5.6%)	2	0/15 (0%)	0	0/8 (0%)	0	0/19 (0%)	0	0/14 (0%)	0	0/10 (0%)	0
Injection site bruising	5/36 (13.9%)	8	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	2	0/14 (0%)	0	0/10 (0%)	0
Injection site haematoma	4/36 (11.1%)	5	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	2	0/14 (0%)	0	0/10 (0%)	0
Injection site haemorrhage	3/36 (8.3%)	6	0/15 (0%)	0	0/8 (0%)	0	0/19 (0%)	0	1/14 (7.1%)	1	1/10 (10%)	1
Injection site induration	0/36 (0%)	0	1/15 (6.7%)	1	0/8 (0%)	0	0/19 (0%)	0	0/14 (0%)	0	0/10 (0%)	0
Injection site pruritus	2/36 (5.6%)	2	0/15 (0%)	0	0/8 (0%)	0	0/19 (0%)	0	0/14 (0%)	0	0/10 (0%)	0
Pyrexia	0/36 (0%)	0	1/15 (6.7%)	1	0/8 (0%)	0	0/19 (0%)	0	2/14 (14.3%)	2	1/10 (10%)	1
Infections and infestations
Conjunctivitis	0/36 (0%)	0	0/15 (0%)	0	1/8 (12.5%)	1	0/19 (0%)	0	0/14 (0%)	0	0/10 (0%)	0
Fungal skin infection	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
Gastroenteritis viral	1/36 (2.8%)	1	0/15 (0%)	0	0/8 (0%)	0	0/19 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0
Gastrointestinal infection	1/36 (2.8%)	1	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
Gingivitis	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	0/19 (0%)	0	0/14 (0%)	0	1/10 (10%)	1
Influenza	1/36 (2.8%)	1	0/15 (0%)	0	0/8 (0%)	0	2/19 (10.5%)	2	1/14 (7.1%)	1	0/10 (0%)	0
Laryngitis	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
Nasopharyngitis	9/36 (25%)	11	1/15 (6.7%)	1	0/8 (0%)	0	6/19 (31.6%)	8	1/14 (7.1%)	1	0/10 (0%)	0
Otitis externa	0/36 (0%)	0	1/15 (6.7%)	1	0/8 (0%)	0	0/19 (0%)	0	0/14 (0%)	0	0/10 (0%)	0
Periodontitis	1/36 (2.8%)	1	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
Pharyngitis	1/36 (2.8%)	1	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	1/10 (10%)	1
Pyoderma	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
Respiratory tract infection	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
Rhinitis	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	2/19 (10.5%)	2	0/14 (0%)	0	0/10 (0%)	0
Tooth abscess	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	0/19 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0
Upper respiratory tract infection	2/36 (5.6%)	2	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	2	2/14 (14.3%)	2	1/10 (10%)	1
Injury, poisoning and procedural complications
Contusion	1/36 (2.8%)	1	1/15 (6.7%)	1	0/8 (0%)	0	0/19 (0%)	0	0/14 (0%)	0	1/10 (10%)	7
Fall	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	0/19 (0%)	0	2/14 (14.3%)	2	0/10 (0%)	0
Ligament sprain	0/36 (0%)	0	1/15 (6.7%)	1	0/8 (0%)	0	0/19 (0%)	0	0/14 (0%)	0	1/10 (10%)	1
Limb injury	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	2	0/14 (0%)	0	0/10 (0%)	0
Muscle rupture	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
Radius fracture	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	0/19 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0
Skin injury	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
Tooth fracture	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	2	0/14 (0%)	0	0/10 (0%)	0
Investigations
Activated partial thromboplastin time prolonged	0/36 (0%)	0	0/15 (0%)	0	1/8 (12.5%)	1	0/19 (0%)	0	0/14 (0%)	0	0/10 (0%)	0
Antithrombin III decreased	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	0/19 (0%)	0	1/14 (7.1%)	2	0/10 (0%)	0
Aspartate aminotransferase increased	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
Basophil count increased	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	0/19 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0
Blood bilirubin increased	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
Blood fibrinogen decreased	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	0/19 (0%)	0	0/14 (0%)	0	1/10 (10%)	1
C-reactive protein increased	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
Fibrin D dimer increased	3/36 (8.3%)	4	2/15 (13.3%)	2	2/8 (25%)	2	1/19 (5.3%)	1	1/14 (7.1%)	1	2/10 (20%)	2
Hepatic enzyme increased	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	0/19 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0
Platelet count decreased	0/36 (0%)	0	0/15 (0%)	0	1/8 (12.5%)	1	0/19 (0%)	0	0/14 (0%)	0	0/10 (0%)	0
Prothrombin fragment 1.2 increased	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	0/19 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0
Prothrombin level increased	3/36 (8.3%)	4	2/15 (13.3%)	2	2/8 (25%)	3	0/19 (0%)	0	0/14 (0%)	0	2/10 (20%)	3
Soluble fibrin monomer complex increased	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	0/19 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0
Thrombin-antithrombin III complex increased	2/36 (5.6%)	3	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	2	0/14 (0%)	0	0/10 (0%)	0
Vitamin D decreased	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
Metabolism and nutrition disorders
Diabetes mellitus	0/36 (0%)	0	1/15 (6.7%)	1	0/8 (0%)	0	0/19 (0%)	0	0/14 (0%)	0	0/10 (0%)	0
Type 2 diabetes mellitus	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	2/19 (10.5%)	2	0/14 (0%)	0	0/10 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	1/36 (2.8%)	1	0/15 (0%)	0	1/8 (12.5%)	1	0/19 (0%)	0	2/14 (14.3%)	2	1/10 (10%)	2
Arthropathy	0/36 (0%)	0	1/15 (6.7%)	1	0/8 (0%)	0	0/19 (0%)	0	0/14 (0%)	0	0/10 (0%)	0
Back pain	4/36 (11.1%)	4	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	2/14 (14.3%)	2	0/10 (0%)	0
Groin pain	1/36 (2.8%)	2	0/15 (0%)	0	1/8 (12.5%)	1	0/19 (0%)	0	0/14 (0%)	0	0/10 (0%)	0
Haemophilic arthropathy	0/36 (0%)	0	1/15 (6.7%)	1	0/8 (0%)	0	1/19 (5.3%)	2	0/14 (0%)	0	0/10 (0%)	0
Muscle spasms	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
Muscle tightness	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
Musculoskeletal chest pain	1/36 (2.8%)	1	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	2	0/14 (0%)	0	0/10 (0%)	0
Musculoskeletal pain	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	0/19 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0
Myalgia	1/36 (2.8%)	2	0/15 (0%)	0	0/8 (0%)	0	0/19 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0
Neck pain	1/36 (2.8%)	1	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	8	0/14 (0%)	0	0/10 (0%)	0
Nervous system disorders
Headache	7/36 (19.4%)	7	1/15 (6.7%)	1	0/8 (0%)	0	2/19 (10.5%)	3	1/14 (7.1%)	1	0/10 (0%)	0
Presyncope	0/36 (0%)	0	1/15 (6.7%)	1	0/8 (0%)	0	0/19 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0
Product Issues
Device physical property issue	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
Psychiatric disorders
Anxiety	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
Renal and urinary disorders
Crystalluria	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
Haematuria	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
Respiratory, thoracic and mediastinal disorders
Catarrh	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
Cough	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	2/19 (10.5%)	2	0/14 (0%)	0	1/10 (10%)	1
Haemoptysis	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
Oropharyngeal pain	0/36 (0%)	0	1/15 (6.7%)	1	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	1/10 (10%)	3
Skin and subcutaneous tissue disorders
Angioedema	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	0/19 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0
Blister	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
Hyperkeratosis	1/36 (2.8%)	1	0/15 (0%)	0	0/8 (0%)	0	0/19 (0%)	0	0/14 (0%)	0	1/10 (10%)	1
Penile ulceration	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
Pruritus	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
Rash	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0
Urticaria	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	0/19 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0
Surgical and medical procedures
Tooth repair	0/36 (0%)	0	0/15 (0%)	0	0/8 (0%)	0	1/19 (5.3%)	1	0/14 (0%)	0	0/10 (0%)	0

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

At the end of the trial, one or more scientific publications may be prepared collaboratively by the investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for up to 60 days to protect intellectual property.

Results Point of Contact

Name/Title	Clinical Transparency and Medical Writing (1452)
Organization	Novo Nordisk A/S
Phone	(+1) 866-867-7178
Email	clinicaltrials@novonordisk.com

Responsible Party:

Novo Nordisk A/S

ClinicalTrials.gov Identifier:

NCT03196297

Other Study ID Numbers:

NN7415-4255
U1111-1179-3872
2016-000614-29
JapicCTI-173682

First Posted:

Jun 22, 2017

Last Update Posted:

Nov 16, 2021

Last Verified:

Nov 1, 2021

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

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