CONCIZUMAB for Haemophilia A with inhibitors | Haemophilia B with inhibitors

Inclusion criteria

• {"criterion_text":"-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\n-Male aged ≥12 years at the time of signing informed consent.\n-Body weight >25 kg at screening\n-Congenital Haemophilia A or B of any severity with documented history of inhibitor (≥0.6 BU).\n-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)."}

Exclusion criteria

• {"criterion_text":"-Known or suspected hypersensitivity to any constituent of the trial product or related products\n-A known systemic inflammatory condition requiring systemic treatment at screening\n-Treatment with emicizumab within 180 days before screening.\n-Ongoing or planned Immune Tolerance Induction treatment\n-Any disorder, except for conditions associated with haemophilia, which in the investigator’s opinion might jeopardise patient’s safety or compliance with the protocol\n-Previous participation in this trial. Participation is defined as signed informed consent. However, this is not applicable for patients who were screen failed at Sponsor’s decision due to the treatment pause.\n-Participation in any clinical trial of an approved or non-approved investigational medicinal product within 5 half-lives or 30 days from screening, whichever is longer (not applicable for patients from NN7415-4310).\n-Platelets ≤ 100x109/L at screening\n-Fibrinogen below laboratory lower normal limit at screening\n-Hepatic dysfunction defined as AST and/or ALT > 3 times the upper limit combined with total bilirubin > 1,5 times the upper limit at screening\n-Renal impairment defined as estimated Glomerular Filtration Rate (eGFR) ≤ 30 ml/min/1.73 m2 for serum creatinine measured at screening\n-Known inherited or acquired coagulation disorder other than congenital haemophilia\n-History of thromboembolic disease. 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 c"}

Primary endpoints

• {"endpoint_text":"-The number of treated spontaneous and traumatic bleeding episodes. 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)","definition_or_measurement_approach":"Count of treated spontaneous and traumatic bleeding episodes recorded per participant during the specified on‑demand and concizumab treatment observation periods (arm 1: from randomisation to start of concizumab; arm 2: from start of concizumab dosing regimen to primary analysis cut-off)."}

Secondary endpoints

• {"endpoint_text":"-Change in SF36v2 bodily pain from start of treatment (week 0) until week 24\n-Change in SF36v2 physical functioning From start of treatment (week 0) until week 24\n-Number of treated spontaneous bleeding episodes 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)\n-Number of treated spontaneous and traumatic joint bleeds 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)\n-Number of treated spontaneous and traumatic target joint bleeds 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)\n-Number of thromboembolic events On demand (arm 1 main part) From randomisation to on demand treatment up until start of concizumab treatment Concizumab (arms 2-4) Before the pause: From start of concizumab treatment (week 0) up until 7 weeks after the treatment was paused as well as After the pause: From start of concizumab treatment (week 0) up until the primary analysis cut-off (at least 32 weeks) Concizumab (arm 1 extension part) From start of the new concizumab dosing regimen (visit 9a) up\n-Number of thromboembolic events Concizumab Before the pause: From start of treatment (week 0) up until 7 weeks after the treatment was paused as well as After the pause: From start of concizumab treatment up until the end of trial (up to 339 weeks)\n-Number of hypersensitivity type reactions On demand (arm 1 main part) From randomisation to on demand treatment up until start of concizumab treatment Concizumab (arms 2-4) Before the pause: From start of concizumab treatment (week 0) up until 7 weeks after the treatment was paused as well as After the pause: From start of concizumab treatment (week 0) up until the primary analysis cut-off (at least 32 weeks) Concizumab (arm 1 extension part) From start of the new concizumab dosing regimen (visi\n-Number of hypersensitivity type reactions Concizumab Before the pause: From start of treatment (week 0) up until 7 weeks after the treatment was paused as well as After the pause: From start of concizumab treatment up until the end of trial (up to 339 weeks)\n-Number of injection site reactions On demand (arm 1 main part) From randomisation to on demand treatment up until start of concizumab treatment Concizumab (arms 2-4) Before the pause: From start of concizumab treatment (week 0b) up until 7 weeks after the treatment was paused as well as After the pause: From start of concizumab treatment (week 0a) up until the primary analysis cut-off (at least 32 weeks) Concizumab (arm 1 extension part) From start of the new concizumab dosing regimen (visit 9a)\n-Number of injection site reactions Concizumab Before the pause: From start of treatment (week 0) up until 7 weeks after the treatment was paused as well as After the pause: From start of concizumab treatment up until the end of trial (up to 339 weeks)\n-Number of patients with antibodies to concizumab Concizumab (arms 2-4) Before the pause: From start of concizumab treatment (week 0) up until 7 weeks after the treatment was paused as well as After the pause: From start of concizumab treatment (week 0) up until the primary analysis cut-off (at least 32 weeks) Concizumab (arm 1 extension part) From start of the new concizumab dosing regimen (visit 9a) up until the primary analysis cut-off\n-Number of patients with antibodies to concizumab Concizumab Before the pause: From start of treatment (week 0) up until 7 weeks after the treatment was paused as well as After the pause: From start of concizumab treatment up until the end of trial (339 weeks)\n-Pre-dose (trough) concizumab plasma concentration (Ctrough) Prior to the concizumab administration at week 24 (after restart)\n-Pre-dose thrombin peak Prior to the concizumab administration at week 24 (after restart)\n-Pre-dose free TFPI concentration Prior to the concizumab administration at week 24 (after restart)\n-Maximum concizumab plasma concentration (Cmax) From 0 to 24 hours where 0 is time of the concizumab dose at week 24 (after restart)\n-Area under the concizumab plasma concentration-time curve (AUC) From 0 to 24 hours where 0 is time of the concizumab dose at week 24 (after restart)","definition_or_measurement_approach":"Secondary endpoints include patient-reported outcome changes (SF36v2 bodily pain and physical functioning) measured from baseline to week 24; counts of specific bleeding event types (treated spontaneous bleeds, joint bleeds, target joint bleeds) recorded during specified observation windows per arm; safety events (thromboembolic events, hypersensitivity reactions, injection site reactions) counted during specified periods (including before/after treatment pause and up to end of trial where specified); immunogenicity (number of patients with antibodies to concizumab) assessed in specified windows; PK/PD measures (Ctrough, thrombin peak, free TFPI, Cmax, AUC) measured around the week 24 dose (0–24h or pre-dose as specified)."}

France

Earliest CTIS Part Ii Submission Date

09-01-2024

Latest Decision Or Authorization Date

12-02-2024

Processing Time Days

34

Number Of Sites

2

Number Of Participants

5

Spain

Earliest CTIS Part Ii Submission Date

09-01-2024

Latest Decision Or Authorization Date

01-02-2024

Processing Time Days

23

Number Of Sites

4

Number Of Participants

8

Portugal

Earliest CTIS Part Ii Submission Date

09-01-2024

Latest Decision Or Authorization Date

31-01-2024

Processing Time Days

22

Number Of Sites

1

Number Of Participants

1

Poland

Earliest CTIS Part Ii Submission Date

06-02-2024

Latest Decision Or Authorization Date

23-02-2024

Processing Time Days

17

Number Of Sites

4

Number Of Participants

11

Sweden

Earliest CTIS Part Ii Submission Date

06-02-2024

Latest Decision Or Authorization Date

05-02-2024

Processing Time Days

27

Number Of Sites

1

Number Of Participants

3

Denmark

Earliest CTIS Part Ii Submission Date

09-01-2024

Latest Decision Or Authorization Date

31-01-2024

Processing Time Days

22

Number Of Sites

1

Number Of Participants

2

Italy

Earliest CTIS Part Ii Submission Date

09-01-2024

Latest Decision Or Authorization Date

26-02-2024

Processing Time Days

48

Number Of Sites

4

Number Of Participants

9

Croatia

Earliest CTIS Part Ii Submission Date

09-01-2024

Latest Decision Or Authorization Date

02-02-2024

Processing Time Days

24

Number Of Sites

1

Number Of Participants

4

Primary sponsor

Full Name

Novo Nordisk A/S

Organisation Type

Pharmaceutical company

Country Of Registered Address

Denmark

Contract research organisations

Name

Celerion Switzerland AG

Responsibilities

Special laboratory

Name

Syneos Health Inc.

Responsibilities

Special laboratory

Name

WCG Clinical Inc.

Name

Perceptive Eclinical Limited

Responsibilities

IWRS Helpdesk

Name

Calyx

Responsibilities

IWRS Supplier

Third parties

• {"country":"Switzerland","full_name":"Celerion Switzerland AG","duties_or_roles":"Special laboratory","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Actigraph LLC","duties_or_roles":"Activity tracker device Supplier","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Oracle America Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"Special laboratory","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Perceptive Eclinical Limited","duties_or_roles":"IWRS Helpdesk","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Calyx","duties_or_roles":"IWRS Supplier","organisation_type":"Industry"}
• {"country":"United States","full_name":"WCG Clinical Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}