Study on the efficacy and safety of Concizumab in patients with hemophilia A and B without inhibitors.

Algeria, Australia, Bosnia and Herzegovina, Bulgaria, Canada, Croatia, Denmark, Estonia, European Union, France, Germany, Hungary, India, Italy, Japan, Korea, Republic of, Lithuania, Malaysia, Mexico, Poland, Portugal, Russian Federation, Serbia, Slovakia, South Africa, Spain, Sweden, Switzerland, Thailand, Turkey, Ukraine, United Kingdom, United States (ICTRP)

ICTRP Trial ID
EUCTR2018-004891-36 (ICTRP)

Official title (approved by ethics committee)
Wirksamkeit und Sicherheit einer prophylaktischen Behandlung mit Concizumab bei Patienten mit Hämophilie A oder B ohne Hemmkörper. (BASEC)

Academic title
Efficacy and Safety of Concizumab prophylaxis in patients with haemophilia A or B without inhibitors - explorer8 (ICTRP)

Public title
Research study to look at how well the drug concizumab works in your body if you have haemophilia without inhibitors (ICTRP)

Disease under investigation
Haemophilia AHaemophilia B
MedDRA version: 20.0Level: LLTClassification code 10018938Term: Haemophilia A (Factor VIII)System Organ Class: 100000004850
MedDRA version: 20.0Level: LLTClassification code 10018939Term: Haemophilia B (Factor IX)System Organ Class: 100000004850;Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] (ICTRP)

Intervention under investigation

Product Name: Concizumab C 100 mg/mL PDS290
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: concizumab
Other descriptive name: CONCIZUMAB
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100-

Product Name: Concizumab C 40 mg/mL PDS290
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: concizumab
Other descriptive name: CONCIZUMAB
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 40-

(ICTRP)

Type of trial
Interventional clinical trial of medicinal product (ICTRP)

Trial design
Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: yes Other trial design description: 2 randomised treatment arms (ppx/no ppx) and two non-randomised treatment arms If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Treatment regimen before entering the trial will determine the assignment to the four treatment arms Number of treatment arms in the trial: 4 (ICTRP)

Inclusion/Exclusion criteria
Gender:
Female: no
Male: yes

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 less than 1%) or B (FIX 2% or less)
Are the trial subjects under 18? yes
Number of subjects for this age range: 35
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 113
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10
(ICTRP)

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.)


Primary and secondary end points
Main Objective: 1. To compare effect of concizumab prophylaxis (PPX) to no prophylaxis (on-demand (OD) treatment with factor) in reducing the number of bleeding episodes in adult and adolescent patients with haemophilia A without inhibitors
2. To compare effect of concizumab prophylaxis to no prophylaxis (on-demand treatment with factor) in reducing the number of bleeding episodes in adult and adolescent patients with haemophilia B without inhibitors;Secondary Objective: 1. To compare the effect of concizumab prophylaxis to the patients? previous prophylaxis treatment in reducing the number of bleeding episodes in adult and adolescent patients with haemophilia A without inhibitors
2. To compare the effect of concizumab prophylaxis to the patients? previous prophylaxis treatment in reducing the number of bleeding episodes in adult and adolescent patients with haemophilia B without inhibitors
3. To investigate the safety of concizumab prophylaxis in adult and adolescent patients with haemophilia A or B without inhibitors
4. To investigate the PK and PD parameters of concizumab prophylaxis in adult and adolescent patients with haemophilia A or B without inhibitors;Primary end point(s): 1. For haemophilia A patients without inhibitors: The number of treated spontaneous and traumatic bleeding episodes
2. For haemophilia B patients without inhibitors: The number of treated spontaneous and traumatic bleeding episodes;Timepoint(s) of evaluation of this end point: 1-2. On demand (arm 1): From randomisation after the pause (week 0) up until start of concizumab treatment (week 24).
Concizumab (arm 2): From start of the new concizumab dosing regimen (week 0) up until the confirmatory analyses cut-off (at least 32 weeks) (ICTRP)

Secondary end point(s): 1. For haemophilia A patients without inhibitors: The number of treated spontaneous and traumatic bleeding episodes
2. For haemophilia B patients without inhibitors: The number of treated spontaneous and traumatic bleeding episodes
3. For haemophilia A patients without inhibitors: Number of treated spontaneous bleeding episodes
4. For haemophilia B patients without inhibitors: Number of treated spontaneous bleeding episodes
5. For haemophilia A patients without inhibitors: Number of treated spontaneous and traumatic joint bleeds
6. For haemophilia B patients without inhibitors: Number of treated spontaneous and traumatic joint bleeds
7. For haemophilia A patients without inhibitors: Number of treated spontaneous and traumatic target joint bleeds
8. For haemophilia B patients without inhibitors: Number of treated spontaneous and traumatic target joint bleeds
9. Number of thromboembolic events
10. Number of thromboembolic events
11. Number of hypersensitivity type reactions
12. Number of hypersensitivity type reactions
13. Number of injection site reactions
14. Number of injection site reactions
15. Number of patients with antibodies to concizumab
16. Number of patients with antibodies to concizumab
17. Pre-dose (trough) concizumab plasma concentration (Ctrough)
18. Pre-dose thrombin peak
19. Pre-dose free tissue factor pathway inhibitor (TFPI) concentration
20. Maximum concizumab plasma concentration (Cmax)
21. Area under the concizumab plasma concentration-time curve (AUC);Timepoint(s) of evaluation of this end point: 1-2:Arm 4:patients on stable PPX min.24wks in trial 4322:
-Previous PPX (in 4322):PPX stable-end of trial(EOT)
-Concizumab (Conci) PPX (in 4307):Maintenance dose is confirmed/increased/decreased?conf. analyses (CA) (min.24wks)
3-8:OD (arm 1):Randomisation post-pause(wk0)-dose start(wk24)
-Conci (arm 2):New regimen start(wk0)?CA(min.32wks)
9,11,13:
OD (arm 1 main part):
-Randomisation?OD treatment (Trt.) to dose start
9,11,13,15:
Conci (arm 2-4):
-Pre-pause:Dose start(wk0)?7wks post Trt. pause
-Post-pause:Dose start(wk0)?the CA(min.32wks)
Conci. (arm-1 Ext. part): Start of Conci. Trt. (wk25) to CA cut-off
10,12,14,16:
Conci:
-Pre-pause:Dose at wk0?7wks after Trt. pause
-Post-pause:dose start?EOT(wk167)
17-19.Prior dosing at wk24(post restart)
20-21.0-24 hrs (0:dose at wk24(post restart)) (ICTRP)

Registration date
10.05.2021 (ICTRP)

Incorporation of the first participant
06.07.2021 (ICTRP)

Secondary sponsors
not available

Additional contacts
Clinical Transparency (1452), clinicaltrials@novonordisk.com, Novo Nordisk A/S (ICTRP)

Secondary trial IDs
NN7415-4307, 2018-004891-36-DK (ICTRP)

Results-Individual Participant Data (IPD)
not available

Further information on the trial
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-004891-36 (ICTRP)