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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04083781




Registration number
NCT04083781
Ethics application status
Date submitted
6/09/2019
Date registered
10/09/2019

Titles & IDs
Public title
Research Study to Look at How Well the Drug Concizumab Works in Your Body if You Have Haemophilia With Inhibitors
Scientific title
Efficacy and Safety of Concizumab Prophylaxis in Patients With Haemophilia A or B With Inhibitors
Secondary ID [1] 0 0
U1111-1225-9670
Secondary ID [2] 0 0
NN7415-4311
Universal Trial Number (UTN)
Trial acronym
explorer7
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Haemophilia A With Inhibitors 0 0
Haemophilia B With 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 - Haemophilia A with inhibitors (HAwI) and haemophilia B with inhibitors (HBwI) patients, previously treated on-demand, will be randomised 1:2 to no prophylaxis versus concizumab prophylaxis. In the extension part, patients in arm 1 will receive daily concizumab subcutaneous (s.c., under the skin) injections.

Experimental: Arm 2: Concizumab prophylaxis - HAwI and HBwI patients, previously treated on-demand, will be randomised 1:2 to no prophylaxis versus concizumab prophylaxis.

Experimental: Arm 3: Concizumab prophylaxis - The HAwI and HBwI patients enrolled into the concizumab phase 2 trial (NN7415-4310) at time of transfer will be offered enrolment into this trial. It is required that these patients are on concizumab prophylaxis up until enrolment into the trial. These patients will continue concizumab prophylaxis.

Experimental: Arm 4: Concizumab prophylaxis - Patients previously on prophylaxis with by-passing agents and on-demand patients who are screened at a timepoint where the required number of patients in arms 1 and 2 have been randomised. These patients will, if eligible, be enrolled into the trial and will initiate concizumab prophylaxis at visit 2a (week 0).


Treatment: Drugs: Concizumab
Concizumab will be administered daily subcutaneously (s.c., under the skin). When patients are randomised to concizumab prophylaxis they will receive a loading dose of 1.0 mg/kg concizumab at visit 2a (week 0: arm 2, 3 \& 4) or visit 9a (week 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 (week 6: arm 2, 3 \& 4) or 9a.3 (week 30: arm 1) and will be based on the concizumab exposure level measured at the previous visit 4a (week 4) or 9a.2 (week 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 bypassing product until visit 9a (week 24: end of main part for arm 1).

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

Outcomes
Primary outcome [1] 0 0
The number of treated spontaneous and traumatic bleeding episodes
Timepoint [1] 0 0
On demand (arm 1): From randomisation (week 0) up until start of concizumab treatment (at least 24 weeks). Concizumab (arm 2): From start of the new concizumab dosing regimen (week 0) up until the primary analysis cut-off (at least 32 weeks)
Secondary outcome [1] 0 0
Change in 36 Item short form health survey version 2 (SF36v2) bodily pain
Timepoint [1] 0 0
From start of treatment (week 0) until week 24. Week 0 is defined as time of randomisation to on-demand administration or time of start of the new concizumab dosing regimen.
Secondary outcome [2] 0 0
Change in SF36v2 physical functioning
Timepoint [2] 0 0
From start of treatment (week 0) until week 24. Week 0 is defined as time of randomisation to on-demand administration or time of start of the new concizumab dosing regimen.
Secondary outcome [3] 0 0
Number of treated spontaneous bleeding episodes
Timepoint [3] 0 0
On demand (arm 1): From randomisation (week 0) up until start of concizumab treatment (at least 24 weeks) Concizumab (arm 2): From start of the new concizumab dosing regimen (week 0) up until the primary analysis cut-off (at least 32 weeks)
Secondary outcome [4] 0 0
Number of treated spontaneous and traumatic joint bleeds
Timepoint [4] 0 0
On demand (arm 1): From randomisation (week 0) up until start of concizumab treatment (at least 24 weeks) Concizumab (arm 2): From start of the new concizumab dosing regimen (week 0) up until the primary analysis cut-off (at least 32 weeks)
Secondary outcome [5] 0 0
Number of treated spontaneous and traumatic target joint bleeds
Timepoint [5] 0 0
On demand (arm 1): From randomisation (week 0) up until start of concizumab treatment (at least 24 weeks) Concizumab (arm 2): From start of the new concizumab dosing regimen (week 0) up until the primary analysis cut-off (at least 32 weeks)
Secondary outcome [6] 0 0
Number of thromboembolic events
Timepoint [6] 0 0
Timeframe is presented under 'outcome measure description'
Secondary outcome [7] 0 0
Number of thromboembolic events
Timepoint [7] 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 280 weeks).
Secondary outcome [8] 0 0
Number of hypersensitivity type reactions
Timepoint [8] 0 0
Timeframe is presented under 'outcome measure description'
Secondary outcome [9] 0 0
Number of hypersensitivity type reactions
Timepoint [9] 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 280 weeks).
Secondary outcome [10] 0 0
Number of injection site reactions
Timepoint [10] 0 0
Timeframe is presented under 'outcome measure description'
Secondary outcome [11] 0 0
Number of injection site reactions
Timepoint [11] 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 280 weeks).
Secondary outcome [12] 0 0
Number of patients with antibodies to concizumab
Timepoint [12] 0 0
Timeframe is presented under 'outcome measure description'
Secondary outcome [13] 0 0
Number of patients with antibodies to concizumab
Timepoint [13] 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 280 weeks).
Secondary outcome [14] 0 0
Pre-dose (trough) concizumab plasma concentration (Ctrough)
Timepoint [14] 0 0
Prior to the concizumab administration at week 24 (after restart)
Secondary outcome [15] 0 0
Pre-dose thrombin peak
Timepoint [15] 0 0
Prior to the concizumab administration at week 24 (after restart)
Secondary outcome [16] 0 0
Pre-dose free tissue factor pathway inhibitor (TFPI) concentration
Timepoint [16] 0 0
Prior to the concizumab administration at week 24 (after restart)
Secondary outcome [17] 0 0
Maximum concizumab plasma concentration (Cmax)
Timepoint [17] 0 0
From 0 to 24 hours where 0 is time of the concizumab dose at week 24 (after restart)
Secondary outcome [18] 0 0
Area under the concizumab plasma concentration-time curve (AUC)
Timepoint [18] 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 Haemophilia A or B of any severity with documented history of inhibitor (equal to or above 0.6 Bethesda Units (BU).
* Patient has been prescribed, or in need of, treatment with bypassing agents in the last 24 weeks prior to screening (for patients not previously enrolled in NN7415-4310 (explorer 4)).
Minimum age
No limit
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.
* Ongoing or planned Immune Tolerance Induction treatment.
* 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
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
The Alfred - Melbourne
Recruitment hospital [2] 0 0
Fiona Stanley Hospital - Haemophilia and Haemostasis Centre - Murdoch
Recruitment postcode(s) [1] 0 0
3004 - Melbourne
Recruitment postcode(s) [2] 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
Missouri
Country [5] 0 0
United States of America
State/province [5] 0 0
North Carolina
Country [6] 0 0
United States of America
State/province [6] 0 0
Tennessee
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
Algeria
State/province [8] 0 0
Algiers
Country [9] 0 0
Algeria
State/province [9] 0 0
Constantine
Country [10] 0 0
Austria
State/province [10] 0 0
Wien
Country [11] 0 0
Bulgaria
State/province [11] 0 0
Sofia
Country [12] 0 0
Croatia
State/province [12] 0 0
Zagreb
Country [13] 0 0
Czechia
State/province [13] 0 0
Praha 2
Country [14] 0 0
Czechia
State/province [14] 0 0
Praha
Country [15] 0 0
Denmark
State/province [15] 0 0
Aarhus N
Country [16] 0 0
France
State/province [16] 0 0
Bron
Country [17] 0 0
France
State/province [17] 0 0
Clermont-Ferrand
Country [18] 0 0
France
State/province [18] 0 0
Le Kremlin-Bicetre
Country [19] 0 0
France
State/province [19] 0 0
Rennes
Country [20] 0 0
India
State/province [20] 0 0
Karnataka
Country [21] 0 0
India
State/province [21] 0 0
Maharashtra
Country [22] 0 0
India
State/province [22] 0 0
New Delhi
Country [23] 0 0
India
State/province [23] 0 0
Tamil Nadu
Country [24] 0 0
Italy
State/province [24] 0 0
FI
Country [25] 0 0
Italy
State/province [25] 0 0
Castelfranco Veneto
Country [26] 0 0
Italy
State/province [26] 0 0
Milano
Country [27] 0 0
Italy
State/province [27] 0 0
Udine
Country [28] 0 0
Italy
State/province [28] 0 0
Verona
Country [29] 0 0
Japan
State/province [29] 0 0
Aichi
Country [30] 0 0
Japan
State/province [30] 0 0
Kagoshima
Country [31] 0 0
Japan
State/province [31] 0 0
Kanagawa
Country [32] 0 0
Japan
State/province [32] 0 0
Nara
Country [33] 0 0
Japan
State/province [33] 0 0
Saitama
Country [34] 0 0
Japan
State/province [34] 0 0
Tokyo
Country [35] 0 0
Korea, Republic of
State/province [35] 0 0
Daejeon
Country [36] 0 0
Korea, Republic of
State/province [36] 0 0
Seoul
Country [37] 0 0
Malaysia
State/province [37] 0 0
Sabah
Country [38] 0 0
Malaysia
State/province [38] 0 0
Ampang, Selangor
Country [39] 0 0
Malaysia
State/province [39] 0 0
Georgetown, Penang
Country [40] 0 0
Mexico
State/province [40] 0 0
Nuevo León
Country [41] 0 0
Norway
State/province [41] 0 0
Oslo
Country [42] 0 0
Poland
State/province [42] 0 0
Mazowieckie
Country [43] 0 0
Poland
State/province [43] 0 0
Malopolskie
Country [44] 0 0
Poland
State/province [44] 0 0
Lublin
Country [45] 0 0
Poland
State/province [45] 0 0
Wroclaw
Country [46] 0 0
Portugal
State/province [46] 0 0
Porto
Country [47] 0 0
Russian Federation
State/province [47] 0 0
Krasnodar
Country [48] 0 0
Russian Federation
State/province [48] 0 0
Moscow
Country [49] 0 0
Russian Federation
State/province [49] 0 0
Petrozavodsk
Country [50] 0 0
Russian Federation
State/province [50] 0 0
Saint-Petersburg
Country [51] 0 0
Serbia
State/province [51] 0 0
Kragujevac
Country [52] 0 0
Slovakia
State/province [52] 0 0
Bratislava
Country [53] 0 0
South Africa
State/province [53] 0 0
Gauteng
Country [54] 0 0
South Africa
State/province [54] 0 0
KwaZulu-Natal
Country [55] 0 0
South Africa
State/province [55] 0 0
Limpopo
Country [56] 0 0
Spain
State/province [56] 0 0
Barcelona
Country [57] 0 0
Spain
State/province [57] 0 0
Madrid
Country [58] 0 0
Spain
State/province [58] 0 0
Málaga
Country [59] 0 0
Spain
State/province [59] 0 0
Oviedo
Country [60] 0 0
Spain
State/province [60] 0 0
Sevilla
Country [61] 0 0
Sweden
State/province [61] 0 0
Solna
Country [62] 0 0
Thailand
State/province [62] 0 0
Bangkok
Country [63] 0 0
Thailand
State/province [63] 0 0
Chiang Mai
Country [64] 0 0
Thailand
State/province [64] 0 0
Ubon Ratchathani
Country [65] 0 0
Turkey
State/province [65] 0 0
Adana
Country [66] 0 0
Turkey
State/province [66] 0 0
Antalya
Country [67] 0 0
Turkey
State/province [67] 0 0
Capa-ISTANBUL
Country [68] 0 0
Ukraine
State/province [68] 0 0
Kyiv
Country [69] 0 0
Ukraine
State/province [69] 0 0
Lviv
Country [70] 0 0
United Kingdom
State/province [70] 0 0
Birmingham
Country [71] 0 0
United Kingdom
State/province [71] 0 0
London
Country [72] 0 0
United Kingdom
State/province [72] 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.