Clinical trial NCT03196284: A Trial Evaluating the Efficacy and Safety of Prophylactic Administration of Concizumab in Haemophilia A and B Patients With Inhibitors
Official title: A Multi-Centre, Randomised, Open-Label, Controlled Trial Evaluating the Efficacy and Safety of Prophylactic Administration of Concizumab in Haemophilia A and B Patients With Inhibitors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Congenital Bleeding Disorder
Haemophilia A With Inhibitors
Haemophilia B With Inhibitors
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2017-06-22
Enrollment: 26
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial is conducted in Africa, Asia, Europe and North America. The aim of the trial is to assess the efficacy of concizumab administered s.c. (subcutaneously, under the skin) once daily in preventing bleeding episodes in haemophilia A and B patients with inhibitors.


Eligibility criteria: 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 the suitability for the trial - Male haemophilia A or B patients with inhibitors aged 18 years or older at the time of signing informed consent - Patients currently in need of treatment with bypassing agents Exclusion Criteria: - Known or suspected hypersensitivity to trial product(s) or related products - Known inherited or acquired bleeding disorder other than haemophilia - Ongoing or planned immune tolerance induction therapy or prophylaxis with FVIII or FIX

Primary outcomes:
measure: The Number of Bleeding Episodes
timeFrame: During at least 24 weeks from treatment onset (week 0)
Secondary outcomes:
measure: The Number of Bleeding Episodes
timeFrame: During at least 76 weeks from treatment onset (week 0)
measure: The Number of Spontaneous Bleeding Episodes
timeFrame: During at least 24 weeks from treatment onset (week 0)
measure: The Number of Spontaneous Bleeding Episodes
timeFrame: During at least 76 weeks from treatment onset (week 0)
measure: Number of Treatment-emergent Adverse Events (TEAEs) During at Least 24 Weeks From Treatment Onset
timeFrame: During at least 24 weeks from treatment onset (week 0)
measure: Number of Treatment-emergent Adverse Events (TEAEs) During at Least 76 Weeks From Treatment Onset
timeFrame: During at least 76 weeks from treatment onset (week 0)
measure: Number of Treatment-emergent Adverse Events (TEAEs) Within 24 Hours After Eptacog Alfa Administration
timeFrame: Within 24 hours after eptacog alfa administration
measure: Occurrence of Anti-concizumab Antibodies During at Least 24 Weeks From Treatment Onset
timeFrame: During at least 24 weeks from treatment onset (week 0)
measure: Occurrence of Anti-concizumab Antibodies During at Least 76 Weeks From Treatment Onset
timeFrame: During at least 76 weeks from treatment onset (week 0)
measure: Change in Fibrinogen
timeFrame: During at least 24 weeks from treatment onset (week 0)
measure: Change in Fibrinogen
timeFrame: During at least 76 weeks from treatment onset (week 0)
measure: Change in D-dimer
timeFrame: During at least 24 weeks from treatment onset (week 0)
measure: Change in D-dimer
timeFrame: During at least 76 weeks from treatment onset (week 0)
measure: Change in Prothrombin Fragment 1 + 2 (F1 + 2)
timeFrame: During at least 24 weeks from treatment onset (week 0)
measure: Change in Prothrombin Fragment 1 + 2 (F1 + 2)
timeFrame: During at least 76 weeks from treatment onset (week 0)
measure: Change in Prothrombin Time (PT)
timeFrame: During at least 24 weeks from treatment onset (week 0)
measure: Change in Prothrombin Time (PT)
timeFrame: During at least 76 weeks from treatment onset (week 0)
measure: Change in Activated Partial Thromboplastin Time (APTT)
timeFrame: During at least 24 weeks from treatment onset (week 0)
measure: Change in Activated Partial Thromboplastin Time (APTT)
timeFrame: During at least 76 weeks from treatment onset (week 0)
measure: Change in Anti-thrombin (AT)
timeFrame: During at least 24 weeks from treatment onset (week 0)
measure: Change in Anti-thrombin (AT)
timeFrame: After at least 76 weeks from treatment onset (week 0)
measure: Concentration of Concizumab
timeFrame: Prior to the last dose administration at 24 weeks
measure: Concentration of Concizumab
timeFrame: Prior to the last dose administration after atleast 76 weeks
measure: Free Tissue Factor Pathway Inhibitor (TFPI) Concentration Value
timeFrame: Prior to the last dose administration at 24 weeks
measure: Free Tissue Factor Pathway Inhibitor (TFPI) Concentration Value
timeFrame: Prior to the last dose administration after atleast 76 weeks
measure: Peak Thrombin Generation
timeFrame: Prior to the last dose administration at 24 weeks
measure: Peak Thrombin Generation
timeFrame: Prior to the last dose administration after atleast 76 weeks
measure: Endogenous Thrombin Potential
timeFrame: Prior to the last dose administration at 24 weeks
measure: Endogenous Thrombin Potential
timeFrame: Prior to the last dose administration after atleast 76 weeks
measure: Thrombin Generation Velocity Index
timeFrame: Prior to the last dose administration at 24 weeks
measure: Thrombin Generation Velocity Index
timeFrame: Prior to the last dose administration after atleast 76 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Indianapolis
country: United States
facility: Novo Nordisk Investigational Site
state: Indiana
city: Iowa City
country: United States
facility: Novo Nordisk Investigational Site
state: Iowa
city: Wien
country: Austria
facility: Novo Nordisk Investigational Site
city: Toronto
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Zagreb
country: Croatia
facility: Novo Nordisk Investigational Site
city: Århus N
country: Denmark
facility: Novo Nordisk Investigational Site
city: Athens
country: Greece
facility: Novo Nordisk Investigational Site
city: Tel-Hashomer
country: Israel
facility: Novo Nordisk Investigational Site
city: Firenze
country: Italy
facility: Novo Nordisk Investigational Site
city: Milano
country: Italy
facility: Novo Nordisk Investigational Site
city: Aichi
country: Japan
facility: Novo Nordisk Investigational Site
city: Nara
country: Japan
facility: Novo Nordisk Investigational Site
city: Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Georgetown, Penang
country: Malaysia
facility: Novo Nordisk Investigational Site
city: Kota Kinabalu
country: Malaysia
facility: Novo Nordisk Investigational Site
city: Madrid
country: Spain
facility: Novo Nordisk Investigational Site
city: Sevilla
country: Spain
facility: Novo Nordisk Investigational Site
city: Solna
country: Sweden
facility: Novo Nordisk Investigational Site
city: Lviv
country: Ukraine
facility: Novo Nordisk Investigational Site
city: London
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Sheffield
country: United Kingdom
facility: Novo Nordisk Investigational Site
Study officials:
References:
citation: Shapiro AD, Angchaisuksiri P, Astermark J, Benson G, Castaman G, Eichler H, Jimenez-Yuste V, Kavakli K, Matsushita T, Poulsen LH, Wheeler AP, Young G, Zupancic-Salek S, Oldenburg J, Chowdary P. Long-term efficacy and safety of subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors. Blood Adv. 2022 Jun 14;6(11):3422-3432. doi: 10.1182/bloodadvances.2021006403.
citation: Shapiro AD, Angchaisuksiri P, Astermark J, Benson G, Castaman G, Chowdary P, Eichler H, Jimenez-Yuste V, Kavakli K, Matsushita T, Poulsen LH, Wheeler AP, Young G, Zupancic-Salek S, Oldenburg J. Subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors: phase 2 trial results. Blood. 2019 Nov 28;134(22):1973-1982. doi: 10.1182/blood.2019001542.