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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04082429




Registration number
NCT04082429
Ethics application status
Date submitted
5/09/2019
Date registered
9/09/2019
Date last updated
11/06/2020

Titles & IDs
Public title
Research Study to Look at How Well the Drug Concizumab Works in Your Body if You Have Haemophilia Without Inhibitors
Scientific title
Efficacy and Safety of Concizumab Prophylaxis in Patients With Haemophilia A or B Without Inhibitors
Secondary ID [1] 0 0
U1111-1225-9722
Secondary ID [2] 0 0
NN7415-4307
Universal Trial Number (UTN)
Trial acronym
explorer8
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Haemophilia A Without Inhibitors 0 0
Haemophilia B Without Inhibitors 0 0
Condition category
Condition code
Blood 0 0 0 0
Clotting disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Concizumab

Experimental: Arm 1: No prophylaxis - Haemophilia A (HA) and haemophilia B (HB) patients), previously treated on-demand, will be randomised 1:2 to no prophylaxis. In the extension phase, this group will receive treatment with concizumab.

Experimental: Arm 2: Concizumab prophylaxis - HA and HB patients, previously treated on-demand, will be randomised 1:2 to concizumab prophylaxis.

Experimental: Arm 3: Concizumab prophylaxis - HA patients, who were enrolled in NN7415-4255 (explorer5) and who were on concizumab prophylaxis up until enrolment into this trial, will continue concizumab prophylaxis.

Experimental: Arm 4: Concizumab prophylaxis - HA and HB patients, who were enrolled in NN7415-4322 (explorer6) and who were previously on prophylaxis with factor products. In addition, arm 4 will also include remaining HA and HB patients from explorer 6 not fulfilling the criteria for arms 1, 2 and 3.


Treatment: Drugs: Concizumab
Concizumab 0.25 mg/kg administered daily subcutaneously (s.c., under the skin). Arms 1, 2 and 4 are starting with a loading dose of 1.0 mg/kg at the first day of dosing. In the extension part patients may increase the dose to 0.35 mg/kg, based on specific criteria.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
For haemophilia A patients without inhibitors: The number of treated bleeding episodes (spontaneous and traumatic) - Count
Timepoint [1] 0 0
From start of treatment (week 0) to the end of the main part (week 24)
Primary outcome [2] 0 0
For haemophilia B patients without inhibitors: The number of treated bleeding episodes (spontaneous and traumatic) - Count
Timepoint [2] 0 0
From start of treatment (week 0) to the end of the main part (week 24)
Secondary outcome [1] 0 0
Annualised bleeding rate (ABR) for treated bleeds for each period: Concizumab and the patient's previous PPX in patients with HA - Count/year
Timepoint [1] 0 0
From start of treatment (week 0) to the end of the main part (week 24)
Secondary outcome [2] 0 0
Annualised bleeding rate (ABR) for treated bleeds for each period: Concizumab and the patient's previous PPX in patients with HB - Count/year
Timepoint [2] 0 0
From start of treatment (week 0) to the end of the main part (week 24)
Secondary outcome [3] 0 0
For haemophilia A patients without inhibitors: Number of treated spontaneous bleeding episodes - Count
Timepoint [3] 0 0
From start of treatment (week 0) to the end of the main part (week 24)
Secondary outcome [4] 0 0
For haemophilia B patients without inhibitors: Number of treated spontaneous bleeding episodes - Count
Timepoint [4] 0 0
From start of treatment (week 0) to the end of the main part (week 24)
Secondary outcome [5] 0 0
For haemophilia A patients without inhibitors: Number of treated joint bleeds - Count
Timepoint [5] 0 0
From start of treatment (week 0) to the end of the main part (week 24)
Secondary outcome [6] 0 0
For haemophilia B patients without inhibitors: Number of treated joint bleeds - Count
Timepoint [6] 0 0
From start of treatment (week 0) to the end of the main part (week 24)
Secondary outcome [7] 0 0
For haemophilia A patients without inhibitors: Number of treated target joint bleeds - Count
Timepoint [7] 0 0
From start of treatment (week 0) to the end of the main part (week 24)
Secondary outcome [8] 0 0
For haemophilia B patients without inhibitors: Number of treated target joint bleeds - Count
Timepoint [8] 0 0
From start of treatment (week 0) to the end of the main part (week 24)
Secondary outcome [9] 0 0
Number of thromboembolic events - Count
Timepoint [9] 0 0
From start of treatment (week 0) to the end of the main part (week 24)
Secondary outcome [10] 0 0
Number of hypersensitivity type reactions - Count
Timepoint [10] 0 0
From start of treatment (week 0) to the end of the main part (week 24)
Secondary outcome [11] 0 0
Number of injection site reactions - Count
Timepoint [11] 0 0
From start of treatment (week 0) to the end of the main part (week 24)
Secondary outcome [12] 0 0
Number of patients with antibodies to concizumab - Count
Timepoint [12] 0 0
From start of treatment (week 0) to the end of the main part (week 24) and end of trial (week 167)
Secondary outcome [13] 0 0
Concizumab plasma concentrations prior to the last prophylaxis dose administration in main part - ng/ml
Timepoint [13] 0 0
Week 24
Secondary outcome [14] 0 0
Peak thrombin generation prior to the last prophylaxis dose administration in main part - nM
Timepoint [14] 0 0
Week 24
Secondary outcome [15] 0 0
Free Tissue Factor Pathway Inhibitor (TFPI) concentration prior to the last prophylaxis dose administration in main part - ng/ml
Timepoint [15] 0 0
Week 24
Secondary outcome [16] 0 0
Concizumab plasma concentration (maximum concentration, Cmax) - ng/ml
Timepoint [16] 0 0
From 0 to 24 hours where 0 is time of prophylaxis dose at week 24
Secondary outcome [17] 0 0
Concizumab plasma concentration (area under the curve, AUC) - ng*hr/ml
Timepoint [17] 0 0
From 0 to 24 hours where 0 is time of prophylaxis dose at week 24

Eligibility
Key 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 suitability for the trial.

- Male aged 12 years or older at the time of signing informed consent.

- Congenital severe haemophilia A (FVIII below 1%) or B (FIX equal to or below 2%).
Minimum age
12 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
- Known or suspected hypersensitivity to monoclonal antibodies.

- Known inherited or acquired coagulation disorder other than congenital haemophilia.

- Presence of confirmed inhibitors equal to or above 0.6 Bethesda Units (BU) at
screening.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Suspended
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC,WA
Recruitment hospital [1] 0 0
Novo Nordisk Investigational Site - Melbourne
Recruitment hospital [2] 0 0
Novo Nordisk Investigational Site - Parkville
Recruitment hospital [3] 0 0
Novo Nordisk Investigational Site - Murdoch
Recruitment postcode(s) [1] 0 0
3004 - Melbourne
Recruitment postcode(s) [2] 0 0
3052 - Parkville
Recruitment postcode(s) [3] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Indiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Iowa
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
North Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Tennessee
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
Algeria
State/province [10] 0 0
Algiers
Country [11] 0 0
Algeria
State/province [11] 0 0
Constantine
Country [12] 0 0
Bulgaria
State/province [12] 0 0
Sofia
Country [13] 0 0
Bulgaria
State/province [13] 0 0
Varna
Country [14] 0 0
Canada
State/province [14] 0 0
Newfoundland and Labrador
Country [15] 0 0
Canada
State/province [15] 0 0
Ontario
Country [16] 0 0
Croatia
State/province [16] 0 0
Zagreb
Country [17] 0 0
Denmark
State/province [17] 0 0
København
Country [18] 0 0
France
State/province [18] 0 0
Brest
Country [19] 0 0
France
State/province [19] 0 0
Caen
Country [20] 0 0
France
State/province [20] 0 0
Le Kremlin Bicetre
Country [21] 0 0
France
State/province [21] 0 0
Nantes Cedex 1
Country [22] 0 0
France
State/province [22] 0 0
Rennes
Country [23] 0 0
Germany
State/province [23] 0 0
Bonn
Country [24] 0 0
Germany
State/province [24] 0 0
Homburg
Country [25] 0 0
India
State/province [25] 0 0
Karnataka
Country [26] 0 0
India
State/province [26] 0 0
Maharashtra
Country [27] 0 0
India
State/province [27] 0 0
Tamil Nadu
Country [28] 0 0
Israel
State/province [28] 0 0
Tel-Hashomer
Country [29] 0 0
Italy
State/province [29] 0 0
Firenze
Country [30] 0 0
Italy
State/province [30] 0 0
Milano
Country [31] 0 0
Italy
State/province [31] 0 0
Roma
Country [32] 0 0
Japan
State/province [32] 0 0
Aichi
Country [33] 0 0
Japan
State/province [33] 0 0
Hiroshima
Country [34] 0 0
Japan
State/province [34] 0 0
Hyogo
Country [35] 0 0
Japan
State/province [35] 0 0
Niigata
Country [36] 0 0
Japan
State/province [36] 0 0
Osaka
Country [37] 0 0
Japan
State/province [37] 0 0
Saitama
Country [38] 0 0
Japan
State/province [38] 0 0
Shizuoka
Country [39] 0 0
Japan
State/province [39] 0 0
Tokyo
Country [40] 0 0
Korea, Republic of
State/province [40] 0 0
Daejeon
Country [41] 0 0
Korea, Republic of
State/province [41] 0 0
Jeju-do
Country [42] 0 0
Korea, Republic of
State/province [42] 0 0
Seoul
Country [43] 0 0
Malaysia
State/province [43] 0 0
Ampang, Selangor
Country [44] 0 0
Mexico
State/province [44] 0 0
Nuevo León
Country [45] 0 0
Poland
State/province [45] 0 0
Krakow
Country [46] 0 0
Poland
State/province [46] 0 0
Lublin
Country [47] 0 0
Poland
State/province [47] 0 0
Poznan
Country [48] 0 0
Poland
State/province [48] 0 0
Warszawa
Country [49] 0 0
Portugal
State/province [49] 0 0
Porto
Country [50] 0 0
Russian Federation
State/province [50] 0 0
Moscow
Country [51] 0 0
Russian Federation
State/province [51] 0 0
Petrozavodsk
Country [52] 0 0
Russian Federation
State/province [52] 0 0
Saint-Petersburg
Country [53] 0 0
Serbia
State/province [53] 0 0
Belgrade
Country [54] 0 0
Serbia
State/province [54] 0 0
Kragujevac
Country [55] 0 0
Serbia
State/province [55] 0 0
Novi Sad
Country [56] 0 0
Slovakia
State/province [56] 0 0
Bratislava
Country [57] 0 0
South Africa
State/province [57] 0 0
Gauteng
Country [58] 0 0
South Africa
State/province [58] 0 0
Limpopo
Country [59] 0 0
Spain
State/province [59] 0 0
Madrid
Country [60] 0 0
Spain
State/province [60] 0 0
Málaga
Country [61] 0 0
Spain
State/province [61] 0 0
Oviedo
Country [62] 0 0
Spain
State/province [62] 0 0
Sevilla
Country [63] 0 0
Spain
State/province [63] 0 0
Valencia
Country [64] 0 0
Sweden
State/province [64] 0 0
Malmö
Country [65] 0 0
Sweden
State/province [65] 0 0
Solna
Country [66] 0 0
Thailand
State/province [66] 0 0
Bangkok
Country [67] 0 0
Turkey
State/province [67] 0 0
Ankara
Country [68] 0 0
Turkey
State/province [68] 0 0
Capa-ISTANBUL
Country [69] 0 0
Turkey
State/province [69] 0 0
Edirne
Country [70] 0 0
Turkey
State/province [70] 0 0
Izmir
Country [71] 0 0
Turkey
State/province [71] 0 0
Samsun
Country [72] 0 0
Ukraine
State/province [72] 0 0
Kyiv
Country [73] 0 0
Ukraine
State/province [73] 0 0
Lviv
Country [74] 0 0
United Kingdom
State/province [74] 0 0
Belfast
Country [75] 0 0
United Kingdom
State/province [75] 0 0
London
Country [76] 0 0
United Kingdom
State/province [76] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novo Nordisk A/S
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study will test how well a new medicine called concizumab works in the body of people
with haemophilia A or B without inhibitors. The purpose is to show that concizumab can
prevent bleeds in the body and is safe to use. Participants who usually only take medicine to
treat bleeds (on-demand) will be placed in one of two groups. In one group participants will
get study medicine from the start of the study. In the other group participants will continue
with their normal medicine and get study medicine after 6 months. The group will be decided
by chance. Participants who usually take medicine to prevent bleeds (prophylaxis treatment)
or who are already being treated with concizumab (study medicine) will receive the study
medicine from the start of the study. Participants will have to inject themselves with study
medicine every day under the skin. This can be done at home. The participant's doctor will
hand out the medicine in the form of a pen-injector. The pen-injector will contain the study
medicine.The study will last for about three years. Participants will have to come to the
clinic for up to 29 times. The time between visits will be approximately 4 weeks for the
first 6 months and approximately 8 weeks for the rest of the study. At all visits, blood
samples will be taken. Participants will be asked to record information into an electronic
diary during the study and may also be asked to wear an activity tracker.
Trial website
https://clinicaltrials.gov/show/NCT04082429
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Reporting Anchor and Disclosure (1452)
Address 0 0
Novo Nordisk A/S
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04082429