HaemostasisPhase 2explorer™5NCT03196297
A Trial Evaluating Efficacy and Safety of Prophylactic Administration of Concizumab in Patients With Severe Haemophilia A Without Inhibitors
A Phase 2 study testing Concizumab and Turoctocog alfa in people with Haemostasis and Haemophilia A, run by Novo Nordisk A/S at 31 sites in 11 countries.
Trial summary
This trial is conducted in Asia, Europe and the United States of America (USA). 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 patients with severe haemophilia A without inhibitors. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Haemostasis, Haemophilia A
- What is being tested?
- Concizumab and Turoctocog alfa
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 31 sitesin 11 countries
- Study dates
- 16 Aug 2017to 3 Jun 2020
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
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 patients aged 18 years or older at the time of signing informed consent, diagnosed with severe haemophilia A (FVIII activity below 1%), based on medical records or results at screening Exclusion Criteria: - Known or suspected hypersensitivity to trial product(s) or related products - Known inherited or acquired bleeding disorder other than haemophilia A - Presence of inhibitors (neutralising antibodies) to Factor VIII (equal to or above 0.6 Bethesda Units) at screening measured by the Nijmegen method
Trial locations and contacts
31 sites in 11 countries.
31 sites in 11 countries
United States5 sites
Novo Nordisk Investigational Site
Indianapolis, Indiana, 46260
Novo Nordisk Investigational Site
Los Angeles, California, 90027
Novo Nordisk Investigational Site
Nashville, Tennessee, 37232
Novo Nordisk Investigational Site
Oklahoma City, Oklahoma, 73104
Novo Nordisk Investigational Site
Salt Lake City, Utah, 84113
Japan4 sites
Novo Nordisk Investigational Site
Aichi, 466-8560
Novo Nordisk Investigational Site
Nara, 634-8522
Novo Nordisk Investigational Site
Tokyo, 160-0023
Novo Nordisk Investigational Site
Tokyo, 167-0035
Turkey (Türkiye)4 sites
Novo Nordisk Investigational Site
Ankara, 06100
Novo Nordisk Investigational Site
Bornova-IZMIR, 35100
Novo Nordisk Investigational Site
Edirne, 22030
Novo Nordisk Investigational Site
Istanbul, 34098
United Kingdom4 sites
Novo Nordisk Investigational Site
Belfast, BT9 7AB
Novo Nordisk Investigational Site
Cambridge, CB2 0QQ
Novo Nordisk Investigational Site
London, NW3 2QG
Novo Nordisk Investigational Site
London, SE1 7EH
France3 sites
Novo Nordisk Investigational Site
Brest, 29609
Novo Nordisk Investigational Site
Caen, 14033
Novo Nordisk Investigational Site
Nantes, 44093
Spain3 sites
Novo Nordisk Investigational Site
Madrid, 28046
Novo Nordisk Investigational Site
Málaga, 29010
Novo Nordisk Investigational Site
Valencia, 46026
Germany2 sites
Novo Nordisk Investigational Site
Bonn, 53127
Novo Nordisk Investigational Site
Homburg, 66421
Italy2 sites
Novo Nordisk Investigational Site
Milan, 20124
Novo Nordisk Investigational Site
Rome, 00168
Sweden2 sites
Novo Nordisk Investigational Site
Malmö, 205 02
Novo Nordisk Investigational Site
Solna, 171 64
About this study
Official title: A Multi-Centre Trial Evaluating Efficacy and Safety of Prophylactic Administration of Concizumab in Patients With Severe Haemophilia A Without Inhibitors
This trial is conducted in Asia, Europe and the United States of America (USA). 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 patients with severe haemophilia A without inhibitors.
- Conditions
- Haemostasis, Haemophilia A
- Being tested
- Concizumab, Turoctocog alfa
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ConcizumabDrug
0.15 mg/kg (with potential stepwise dose administration to 0.25 mg/kg) administered daily s.c (subcutaneously, under the skin). Treatment duration is 24 weeks in the main phase, and 52 weeks in the extension phase
Turoctocog alfaDrug
Breakthrough bleeding episodes will be treated by the patients at home with turoctocog alfa at the discretion of the study doctor, who will also choose dose levels
| Study group | Role | What they receive |
|---|---|---|
| Concizumab | Experimental | Daily administration of concizumab to both on-demand and prophylaxis patients Receives: Drug: Concizumab; Drug: Turoctocog alfa |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Number of Bleeding Episodes During at Least 24 Weeks From Treatment Onset
The number of bleeding episodes that were treated during at least 24 weeks from treatment onset are presented. The data is presented while on last dose level when the bleed occurred.
Measured: During at least 24 weeks from treatment onset
Secondary outcomes (29)
The Number of Bleeding Episodes During at Least 76 Weeks From Treatment Onset
The number of bleeding episodes that were treated during at least 76 weeks from treatment onset are presented. The data is presented while on last dose level when the bleed occurred.
Measured: During at least 76 weeks from treatment onset
The Number of Spontaneous Bleeding Episodes During at Least 24 Weeks From Treatment Onset
Bleeds that were not linked to a specific, known action or event are called spontaneous bleeding episodes. The number of spontaneous bleeding episodes that were treated during at least 24 weeks from treatment onset are presented. The data is presented while on last dose level when the bleed occurred.
Measured: During at least 24 weeks from treatment onset
The Number of Spontaneous Bleeding Episodes During at Least 76 Weeks From Treatment Onset
Bleeds that were not linked to a specific, known action or event are called spontaneous bleeding episodes. The number of spontaneous bleeding episodes that were treated during at least 76 weeks from treatment onset are presented. The data is presented while on last dose level when the bleed occurred.
Measured: During at least 76 weeks from treatment onset
Number of Treatment-emergent Adverse Events (TEAEs) During at Least 24 Weeks From Treatment Onset
An adverse event (AE) was any untoward medical occurrence in a participant administered a medicinal product, and which does not necessarily had a causal relationship with this treatment. A TEAE was defined as an event that had onset from the first exposure to treatment until the last visit in the trial. Number of TEAEs that occurred during at least 24 weeks from treatment onset (week 0) are presented. The data is presented per dose level participants were on at the time of onset of the adverse event.
Measured: During at least 24 weeks from treatment onset (week 0)
Number of Treatment-emergent Adverse Events (TEAEs) During at Least 76 Weeks From Treatment Onset
An adverse event (AE) was any untoward medical occurrence in a participant administered a medicinal product, and which does not necessarily had a causal relationship with this treatment. A TEAE was defined as an event that had onset from the first exposure to treatment until the last visit in the trial. Number of TEAEs that occurred during at least 76 weeks from treatment onset (week 0) are presented. The data is presented per dose level participants were on at the time of onset of the adverse event.
Measured: During at least 76 weeks from treatment onset (week 0)
Occurrence of Anti-concizumab Antibodies During at Least 24 Weeks From Treatment Onset
Occurrence of anti-concizumab antibodies during at least 24 weeks from treatment onset (week 0) is presented. In the reported data, 'Yes' infers number of participants who showed positive anti-concizumab antibody tests whereas 'No' infers number of participants who showed negative anti-concizumab antibody tests.
Measured: During at least 24 weeks from treatment onset (week 0)
Occurrence of Anti-concizumab Antibodies During at Least 76 Weeks From Treatment Onset
Occurrence of anti-concizumab antibodies during at least 76 weeks from treatment onset (week 0) is presented. In the reported data, 'Yes' infers number of participants who showed positive anti-concizumab antibody tests whereas 'No' infers number of participants who showed negative anti-concizumab antibody tests.
Measured: During at least 76 weeks from treatment onset (week 0)
Change in Fibrinogen During 24 Weeks From Treatment Onset
Change in fibrinogen during 24 weeks from treatment onset (week 0) is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.
Measured: During 24 weeks from treatment onset (week 0)
Change in Fibrinogen During at Least 76 Weeks From Treatment Onset
Change in fibrinogen during at least 76 weeks from treatment onset (week 0) is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.
Measured: During at least 76 weeks from treatment onset (week 0)
Change in D-dimer During 24 Weeks From Treatment Onset
Change in D-dimer during at least 24 weeks from treatment onset (week 0) is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.
Measured: During 24 weeks from treatment onset (week 0)
Change in D-dimer During at Least 76 Weeks From Treatment Onset
Change in D-dimer during at least 76 weeks from treatment onset (week 0) is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.
Measured: During at least 76 weeks from treatment onset (week 0)
Change in Prothrombin Fragment 1 + 2 (F1 + F2) During 24 Weeks From Treatment Onset
Change in F1 + F2 during 24 weeks from treatment onset (week 0) is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.
Measured: During 24 weeks from treatment onset (week 0)
Change in Prothrombin Fragment 1 + 2 (F1 + F2) During at Least 76 Weeks From Treatment Onset
Change in F1 + F2 during at least 76 weeks from treatment onset (week 0) is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.
Measured: During at least 76 weeks from treatment onset (week 0)
Change in Prothrombin Time (PT) During 24 Weeks From Treatment Onset
Change in PT during 24 weeks from treatment onset (week 0) is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.
Measured: During 24 weeks from treatment onset (week 0)
Change in Prothrombin Time (PT) During at Least 76 Weeks From Treatment Onset
Change in PT during at least 76 weeks from treatment onset (week 0) is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.
Measured: During at least 76 weeks from treatment onset (week 0)
Change in Activated Partial Thromboplastin Time (APTT) During 24 Weeks From Treatment Onset
Change in APTT during 24 weeks from treatment onset (week 0) is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.
Measured: During 24 weeks from treatment onset (week 0)
Change in Activated Partial Thromboplastin Time (APTT) During at Least 76 Weeks From Treatment Onset
Change in APTT during at least 76 weeks from treatment onset (week 0) is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.
Measured: During at least 76 weeks from treatment onset (week 0)
Change in Anti-thrombin (AT) During 24 Weeks From Treatment Onset
Change in AT during 24 weeks from treatment onset (week 0) is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.
Measured: During 24 weeks from treatment onset (week 0)
Change in Anti-thrombin (AT) After at Least 76 Weeks From Treatment
Change in AT after at least 76 weeks from treatment onset (week 0) is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.
Measured: During at least 76 weeks from treatment onset (week 0)
Concentration of Concizumab Prior to the Last Dose Administration at 24 Weeks
Concentration of concizumab prior to the last dose administration at 24 weeks is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.
Measured: Prior to the last dose administration at 24 weeks
Concentration of Concizumab Prior to the Last Dose Administration After at Least 76 Weeks
Concentration of concizumab prior to the last dose administration after at least 76 weeks is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.
Measured: Prior to the last dose administration after at least 76 weeks
Free Tissue Factor Pathway Inhibitor (TFPI) Concentration Value Prior to the Last Dose Administration at 24 Weeks
Free TFPI (TFPI not bound to concizumab) concentration value prior to the last dose administration at 24 weeks is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.
Measured: Prior to the last dose administration at 24 weeks
Free Tissue Factor Pathway Inhibitor (TFPI) Concentration Value Prior to the Last Dose Administration After at Least 76 Weeks
Free TFPI concentration value prior to the last dose administration after at least 76 weeks is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.
Measured: Prior to the last dose administration after at least 76 weeks
Peak Thrombin Generation Prior to the Last Dose Administration at 24 Weeks
Peak thrombin generation is the maximal concentration of thrombin formed at a given point in time. Peak thrombin generation prior to the last dose administration at 24 weeks is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.
Measured: Prior to the last dose administration at 24 weeks
Peak Thrombin Generation Prior to the Last Dose Administration After at Least 76 Weeks
Peak thrombin generation is the maximal concentration of thrombin formed at a given point in time. Peak thrombin generation prior to the last dose administration after at least 76 weeks is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.
Measured: Prior to the last dose administration after at least 76 weeks
Endogenous Thrombin Potential Prior to the Last Dose Administration at 24 Weeks
The endogenous thrombin potential (ETP), defined as the amount of thrombin which can be generated after the in vitro activation of coagulation with tissue factor as trigger and phospholipids as platelet substitute. Endogenous thrombin potential prior to the last dose administration at 24 weeks is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.
Measured: Prior to the last dose administration at 24 weeks
Endogenous Thrombin Potential Prior to the Last Dose Administration After at Least 76 Weeks
The endogenous thrombin potential (ETP), defined as the amount of thrombin which can be generated after the in vitro activation of coagulation with tissue factor as trigger and phospholipids as platelet substitute. Endogenous thrombin potential prior to the last dose administration after at least 76 weeks is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.
Measured: Prior to the last dose administration after at least 76 weeks
Thrombin Generation Velocity Index Prior to the Last Dose Administration at 24 Weeks
Thrombin generation velocity index represents the effective rate of thrombin generation between lag time and time to peak. Thrombin generation velocity index prior to the last dose administration at 24 weeks is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.
Measured: Prior to the last dose administration at 24 weeks
Thrombin Generation Velocity Index Prior to the Last Dose Administration After at Least 76 Weeks
Thrombin generation velocity index represents the effective rate of thrombin generation between lag time and time to peak. Thrombin generation velocity index prior to the last dose administration after at least 76 weeks is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.
Measured: Prior to the last dose administration after at least 76 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2017
- Study start16 Aug 2017
- Primary completion22 Jun 2018
- Study completion3 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HaemostasisStudies of the same condition, open and under way.
- More trials run by Novo Nordisk A/SThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novo Nordisk A/S
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03196297
- Sponsor's protocol ID
- NN7415-4255
- Other IDs
- U1111-1179-3872, 2016-000614-29, JapicCTI-173682, 2016
- Acronym
- explorer™5
- Status last verified
- Nov 2021
- First submitted
- 20 Jun 2017
- Last updated
- 16 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
Publications
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.
PubMed 35290453Shapiro 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.
PubMed 31444162