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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04082429
Ethics application status
Date submitted
5/09/2019
Date registered
9/09/2019

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(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Concizumab

Experimental: Arm 1: No prophylaxis (PPX) - Haemophilia A (HA) and haemophilia B (HB) patients, previously treated on-demand, will be randomised 1:2 to no prophylaxis versus concizumab 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 no prophylaxis versus concizumab prophylaxis.

Experimental: Arm 3: Concizumab prophylaxis - The HA patients enrolled into the concizumab phase 2 trial NN7415-4255 (explorer 5) will be offered enrolment into this arm.

Experimental: Arm 4: Concizumab prophylaxis - Arm 4 will include patients previously on prophylaxis with factor products with a minimum of 24 weeks observation in NN7415-4322 (explorer 6) (at least 30 HA and 30 HB patients).

In addition, arm 4 will also include: 1) Patients who were randomised to arms 1 and 2 before the treatment pause. 2) HA patients who were in NN7415-4255 (explorer 5) at the time of the treatment pause, and who have now completed explorer 5. 3) On demand patients included after arms 1 and 2 are closed.


Treatment: Drugs: Concizumab
When patients are randomised/allocated to concizumab prophylaxis, they will receive a loading dose of 1.0 mg/kg concizumab at visit 2a (week (Wk) 0) (arm 2, 3 and 4) or visit 9a (Wk 24) (arm 1) followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week dose adjustment period on 0.20 mg/kg concizumab, the patients can be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab. A potential dose adjustment will take place at visit 4a.1 (Wk 6) or 9a.3 (Wk 30) and will be based on the concizumab exposure level measured at the previous visit 4a (Wk 6) or 9a.2 (Wk 28). Patients who have concizumab exposure levels of 200-4000 ng/mL will stay at 0.20 mg/kg concizumab. Patients in arm 1 will continue on-demand treatment with their usual replacement therapy until visit 9a (week 24; end of main part). In the extension part, patients in arm 1 will receive daily concizumab subcutaneous injections.
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 spontaneous and traumatic bleeding episodes
Timepoint [1] 0 0
On demand (arm 1): From randomisation after the pause (Wk 0) up until start of concizumab treatment (Wk 24). Concizumab (arm 2): From start of the new concizumab dosing regimen (Wk 0) up until the confirmatory analyses cut-off (at least 32 weeks)
Primary outcome [2] 0 0
For haemophilia B patients without inhibitors: The number of treated spontaneous and traumatic bleeding episodes
Timepoint [2] 0 0
On demand (arm 1): From randomisation after the pause (Wk 0) up until start of concizumab treatment (Wk 24). Concizumab (arm 2): From start of the new concizumab dosing regimen (Wk 0) up until the confirmatory analyses cut-off (at least 32 weeks)
Secondary outcome [1] 0 0
For haemophilia A patients without inhibitors: The number of treated spontaneous and traumatic bleeding episodes
Timepoint [1] 0 0
Time frame is presented under 'outcome measure description'
Secondary outcome [2] 0 0
For haemophilia B patients without inhibitors: The number of treated spontaneous and traumatic bleeding episodes
Timepoint [2] 0 0
Time frame is presented under 'outcome measure description'
Secondary outcome [3] 0 0
For haemophilia A patients without inhibitors: Number of treated spontaneous bleeding episodes
Timepoint [3] 0 0
On demand (arm 1): From randomisation after the pause (Wk 0) up until start of concizumab treatment (Wk 24). Concizumab (arm 2): From start of the new concizumab dosing regimen (Wk 0) up until the confirmatory analyses cut-off (at least 32 weeks)
Secondary outcome [4] 0 0
For haemophilia B patients without inhibitors: Number of treated spontaneous bleeding episodes
Timepoint [4] 0 0
On demand (arm 1): From randomisation after the pause (Wk 0) up until start of concizumab treatment (Wk 24). Concizumab (arm 2): From start of the new concizumab dosing regimen (Wk 0) up until the confirmatory analyses cut-off (at least 32 weeks)
Secondary outcome [5] 0 0
For haemophilia A patients without inhibitors: Number of treated spontaneous and traumatic joint bleeds
Timepoint [5] 0 0
On demand (arm 1): From randomisation after the pause (Wk 0) up until start of concizumab treatment (Wk 24). Concizumab (arm 2): From start of the new concizumab dosing regimen (Wk 0) up until the confirmatory analyses cut-off (at least 32 weeks)
Secondary outcome [6] 0 0
For haemophilia B patients without inhibitors: Number of treated spontaneous and traumatic joint bleeds
Timepoint [6] 0 0
On demand (arm 1): From randomisation after the pause (Wk 0) up until start of concizumab treatment (Wk 24). Concizumab (arm 2): From start of the new concizumab dosing regimen (Wk 0) up until the confirmatory analyses cut-off (at least 32 weeks)
Secondary outcome [7] 0 0
For haemophilia A patients without inhibitors: Number of treated spontaneous and traumatic target joint bleeds
Timepoint [7] 0 0
On demand (arm 1): From randomisation after the pause (Wk 0) up until start of concizumab treatment (Wk 24). Concizumab (arm 2): From start of the new concizumab dosing regimen (Wk 0) up until the confirmatory analyses cut-off (at least 32 weeks)
Secondary outcome [8] 0 0
For haemophilia B patients without inhibitors: Number of treated spontaneous and traumatic target joint bleeds
Timepoint [8] 0 0
On demand (arm 1): From randomisation after the pause (Wk 0) up until start of concizumab treatment (Wk 24). Concizumab (arm 2): From start of the new concizumab dosing regimen (Wk 0) up until the confirmatory analyses cut-off (at least 32 weeks)
Secondary outcome [9] 0 0
Number of thromboembolic events
Timepoint [9] 0 0
Time frame is presented under 'outcome measure description'.
Secondary outcome [10] 0 0
Number of thromboembolic events
Timepoint [10] 0 0
Concizumab: Before the pause: From start of treatment (week 0) up until 7 weeks after the treatment was paused. After the pause: From start of concizumab treatment up until the end of trial (up to 296 weeks).
Secondary outcome [11] 0 0
Number of hypersensitivity type reactions
Timepoint [11] 0 0
Time frame is presented under 'outcome measure description'.
Secondary outcome [12] 0 0
Number of hypersensitivity type reactions
Timepoint [12] 0 0
Concizumab: Before the pause: From start of treatment (week 0) up until 7 weeks after the treatment was paused. After the pause: From start of concizumab treatment up until the end of trial (up to 296 weeks).
Secondary outcome [13] 0 0
Number of injection site reactions
Timepoint [13] 0 0
Time frame is presented under 'outcome measure description'.
Secondary outcome [14] 0 0
Number of injection site reactions
Timepoint [14] 0 0
Concizumab: Before the pause: From start of treatment (week 0) up until 7 weeks after the treatment was paused. After the pause: From start of concizumab treatment up until the end of trial (up to 296 weeks).
Secondary outcome [15] 0 0
Number of patients with antibodies to concizumab
Timepoint [15] 0 0
Time frame is presented under 'outcome measure description'.
Secondary outcome [16] 0 0
Number of patients with antibodies to concizumab
Timepoint [16] 0 0
Concizumab: Before the pause: From start of treatment (week 0) up until 7 weeks after the treatment was paused. After the pause: From start of concizumab treatment up until the end of trial (up to 296 weeks).
Secondary outcome [17] 0 0
Pre-dose (trough) concizumab plasma concentration (Ctrough)
Timepoint [17] 0 0
Prior to the concizumab administration at week 24 (after restart)
Secondary outcome [18] 0 0
Pre-dose thrombin peak
Timepoint [18] 0 0
Prior to the concizumab administration at week 24 (after restart)
Secondary outcome [19] 0 0
Pre-dose free tissue factor pathway inhibitor (TFPI) concentration
Timepoint [19] 0 0
Prior to the concizumab administration at week 24 (after restart)
Secondary outcome [20] 0 0
Maximum concizumab plasma concentration (Cmax)
Timepoint [20] 0 0
From 0 to 24 hours where 0 is time of the concizumab dose at week 24 (after restart)
Secondary outcome [21] 0 0
Area under the concizumab plasma concentration-time curve (AUC)
Timepoint [21] 0 0
From 0 to 24 hours where 0 is time of the concizumab dose at week 24 (after restart)

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
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
* Known or suspected hypersensitivity to any constituent of the trial product or related products.
* Known inherited or acquired coagulation disorder other than congenital haemophilia.
* Presence of confirmed inhibitors 0.6 BU or greater at screening.
* History of thromboembolic disease (includes arterial and venous thrombosis including myocardial infarction, pulmonary embolism, cerebral infarction/thrombosis, deep vein thrombosis, other clinically significant thromboembolic events and peripheral artery occlusion). Current clinical signs of, or treatment for thromboembolic disease. Patients who in the judgement of the investigator are considered at high risk of thromboembolic events (thromboembolic risk factors could include, but are not limited to, hypercholesterolemia, diabetes mellitus, hypertension, obesity, smoking, family history of thromboembolic events, arteriosclerosis, other conditions associated with increased risk of thromboembolic events.)

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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/11/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
9/06/2026
Actual
Sample size
Target
158
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC,WA
Recruitment hospital [1] 0 0
The Alfred - Melbourne
Recruitment hospital [2] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [3] 0 0
Fiona Stanley Hospital - Haemophilia and Haemostasis Centre - 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
Michigan
Country [3] 0 0
United States of America
State/province [3] 0 0
Pennsylvania
Country [4] 0 0
United States of America
State/province [4] 0 0
Tennessee
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
United States of America
State/province [6] 0 0
Wisconsin
Country [7] 0 0
Algeria
State/province [7] 0 0
Algiers
Country [8] 0 0
Algeria
State/province [8] 0 0
Constantine
Country [9] 0 0
Bosnia and Herzegovina
State/province [9] 0 0
Banja Luka
Country [10] 0 0
Bulgaria
State/province [10] 0 0
Sofia
Country [11] 0 0
Canada
State/province [11] 0 0
Ontario
Country [12] 0 0
Croatia
State/province [12] 0 0
Zagreb
Country [13] 0 0
Denmark
State/province [13] 0 0
København
Country [14] 0 0
Estonia
State/province [14] 0 0
Tallinn
Country [15] 0 0
France
State/province [15] 0 0
Brest
Country [16] 0 0
France
State/province [16] 0 0
Caen
Country [17] 0 0
France
State/province [17] 0 0
Le Kremlin Bicetre
Country [18] 0 0
France
State/province [18] 0 0
Rennes
Country [19] 0 0
Germany
State/province [19] 0 0
Homburg
Country [20] 0 0
Hungary
State/province [20] 0 0
Budapest
Country [21] 0 0
India
State/province [21] 0 0
Karnataka
Country [22] 0 0
India
State/province [22] 0 0
Maharashtra
Country [23] 0 0
India
State/province [23] 0 0
Rajasthan
Country [24] 0 0
Israel
State/province [24] 0 0
Tel-Hashomer
Country [25] 0 0
Italy
State/province [25] 0 0
Torino
Country [26] 0 0
Japan
State/province [26] 0 0
Aichi
Country [27] 0 0
Japan
State/province [27] 0 0
Hiroshima
Country [28] 0 0
Japan
State/province [28] 0 0
Hyogo
Country [29] 0 0
Japan
State/province [29] 0 0
Osaka
Country [30] 0 0
Japan
State/province [30] 0 0
Saitama
Country [31] 0 0
Japan
State/province [31] 0 0
Shizuoka
Country [32] 0 0
Japan
State/province [32] 0 0
Tokyo
Country [33] 0 0
Korea, Republic of
State/province [33] 0 0
Daejeon
Country [34] 0 0
Korea, Republic of
State/province [34] 0 0
Jeju-do
Country [35] 0 0
Korea, Republic of
State/province [35] 0 0
Seoul
Country [36] 0 0
Lithuania
State/province [36] 0 0
Vilnius
Country [37] 0 0
Malaysia
State/province [37] 0 0
Ampang, Selangor
Country [38] 0 0
Mexico
State/province [38] 0 0
Nuevo León
Country [39] 0 0
Poland
State/province [39] 0 0
Mazowieckie
Country [40] 0 0
Poland
State/province [40] 0 0
Malopolskie
Country [41] 0 0
Poland
State/province [41] 0 0
Wielkopolskie
Country [42] 0 0
Poland
State/province [42] 0 0
Lublin
Country [43] 0 0
Portugal
State/province [43] 0 0
Porto
Country [44] 0 0
Russian Federation
State/province [44] 0 0
Krasnodar
Country [45] 0 0
Russian Federation
State/province [45] 0 0
Moscow
Country [46] 0 0
Russian Federation
State/province [46] 0 0
Petrozavodsk
Country [47] 0 0
Russian Federation
State/province [47] 0 0
Saint-Petersburg
Country [48] 0 0
Serbia
State/province [48] 0 0
Belgrade
Country [49] 0 0
Serbia
State/province [49] 0 0
Kragujevac
Country [50] 0 0
Serbia
State/province [50] 0 0
Novi Sad
Country [51] 0 0
South Africa
State/province [51] 0 0
Limpopo
Country [52] 0 0
Spain
State/province [52] 0 0
Madrid
Country [53] 0 0
Spain
State/province [53] 0 0
Málaga
Country [54] 0 0
Spain
State/province [54] 0 0
Sevilla
Country [55] 0 0
Sweden
State/province [55] 0 0
Malmö
Country [56] 0 0
Sweden
State/province [56] 0 0
Solna
Country [57] 0 0
Switzerland
State/province [57] 0 0
Zürich
Country [58] 0 0
Thailand
State/province [58] 0 0
Bangkok
Country [59] 0 0
Turkey
State/province [59] 0 0
Besevler/Ankara
Country [60] 0 0
Turkey
State/province [60] 0 0
Adana
Country [61] 0 0
Turkey
State/province [61] 0 0
Ankara
Country [62] 0 0
Turkey
State/province [62] 0 0
Capa-ISTANBUL
Country [63] 0 0
Turkey
State/province [63] 0 0
Edirne
Country [64] 0 0
Turkey
State/province [64] 0 0
Izmir
Country [65] 0 0
Turkey
State/province [65] 0 0
Samsun
Country [66] 0 0
Ukraine
State/province [66] 0 0
Kyiv
Country [67] 0 0
Ukraine
State/province [67] 0 0
Lviv
Country [68] 0 0
United Kingdom
State/province [68] 0 0
Belfast
Country [69] 0 0
United Kingdom
State/province [69] 0 0
London
Country [70] 0 0
United Kingdom
State/province [70] 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
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://novonordisk-trials.com


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04082429