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Research Study to Look at How Well the Drug Concizumab Works in Your Body if You Have Haemophilia With Inhibitors (explorer7)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04083781
Recruitment Status : Suspended (The decision to pause the trial is a result of the occurrence of non-fatal thrombotic events in three patients enrolled in the ongoing phase 3 programme.)
First Posted : September 10, 2019
Last Update Posted : March 26, 2020
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Study Description
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Brief Summary:
This study will test how well a new medicine called concizumab works in the body of people with haemophilia A or B with inhibitors. The purpose is to show that concizumab can prevent bleeds in the body and is safe to use. Participants who usually only take medicine to treat bleeds (on-demand) will be placed in one of two groups. In one group participants will get study medicine from the start of the study. In the other group participants will continue with their normal medicine and get study medicine after 6 months. The group will be decided by chance. Participants who usually take medicine to prevent bleeds (prophylaxis treatment) or who are already being treated with concizumab (study medicine) will receive the study medicine from the start of the study. Participants will have to inject themselves with study medicine every day under the skin. This can be done at home. The participant's doctor will hand out the medicine in the form of a pen-injector. The pen-injector will contain the study medicine. The study will last for about three years. Participants will have to come to the clinic for up to 29 times. The time between visits will be approximately 4 weeks for the first 6 months and approximately 8 weeks for the rest of the study. At all visits, blood samples will be taken. Participants will be asked to record information into an electronic diary during the study and may also be asked to wear an activity tracker.

Condition or disease Intervention/treatment Phase
Haemophilia A With Inhibitors Haemophilia B With Inhibitors Drug: Concizumab Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 152 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Patients will be randomised to concizumab prophylaxis (ppx) or no ppx or assigned into the non-randomised treatment arms, based on their treatment regimen before entering the trial. The main part of the trial is completed for a patient when the patient has completed 24 weeks of participation (screening period not included). Patients randomised into arm 1 will continue on-demand treatment with their usual bypassing product/s until visit 9 (week 24, end of main part).After the main part of the trial (visit 9), all patients will be offered to continue in the extension part of the trial and receive treatment with concizumab for up to an additional 136 weeks. After 136 weeks in extension part the patient will enter the safety follow-up part of the trial. The follow-up part of the trial lasts for 7 weeks and the patient will continue to report bleeding episodes until visit 27 (week 167). The patient will receive his last dose on visit 26 (week 160)
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Concizumab Prophylaxis in Patients With Haemophilia A or B With Inhibitors
Actual Study Start Date : October 21, 2019
Estimated Primary Completion Date : October 30, 2020
Estimated Study Completion Date : March 10, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hemophilia

Arms and Interventions
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Arm Intervention/treatment
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. In the extension phase, this group will receive treatment with concizumab.
 Drug: Concizumab
Concizumab 0.25 mg/kg administered daily subcutaneously (s.c., under the skin). Arms 1, 2 and 4 are starting with a loading dose of 1.0 mg/kg at the first day of dosing. In the extension part patients may increase the dose to 0.35 mg/kg, based on specific criteria.
Experimental: Arm 2: Concizumab prophylaxis
HAwI and HBwI patients, previously treated on-demand, will be randomised 1:2 to concizumab prophylaxis.
 Drug: Concizumab
Concizumab 0.25 mg/kg administered daily subcutaneously (s.c., under the skin). Arms 1, 2 and 4 are starting with a loading dose of 1.0 mg/kg at the first day of dosing. In the extension part patients may increase the dose to 0.35 mg/kg, based on specific criteria.
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.
 Drug: Concizumab
Concizumab 0.25 mg/kg administered daily subcutaneously (s.c., under the skin). Arms 1, 2 and 4 are starting with a loading dose of 1.0 mg/kg at the first day of dosing. In the extension part patients may increase the dose to 0.35 mg/kg, based on specific criteria.
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 2.
 Drug: Concizumab
Concizumab 0.25 mg/kg administered daily subcutaneously (s.c., under the skin). Arms 1, 2 and 4 are starting with a loading dose of 1.0 mg/kg at the first day of dosing. In the extension part patients may increase the dose to 0.35 mg/kg, based on specific criteria.


Outcome Measures
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Primary Outcome Measures :
  1. The number of treated bleeding episodes (spontaneous and traumatic) [ Time Frame: From start of treatment (week 0) to the end of the main part (week 24) ]
    Count


Secondary Outcome Measures :
  1. Change in Short Form (36) Health Survey, verrsion 2 (SF36v2) bodily pain [ Time Frame: From start of treatment (week 0) to the end of the main part (week 24) ]
    The Bodily Pain subscale of the SF-36v2 questionnaire consists of 2 items. Subscale scores range from 0-100 and are transformed into population norm adjusted T-scores. A higher score indicates a better outcome on this subscale.

  2. Change in SF36v2 physical functioning [ Time Frame: From start of treatment (week 0) to the end of the main part (week 24) ]
    The Physical Function subscale of the SF-36v2 questionnaire consists of 1 item with 10 subitems. Subscale scores range from 0-100 and are transformed into population norm adjusted T-scores. A higher score indicates a better outcome on this subscale.

  3. Number of treated spontaneous bleeding episodes [ Time Frame: From start of treatment (week 0) to the end of the main part (week 24) ]
    Count

  4. Number of treated joint bleeds [ Time Frame: From start of treatment (week 0) to the end of the main part (week 24) ]
    Count

  5. Number of treated target joint bleeds [ Time Frame: From start of treatment (week 0) to the end of the main part (week 24) ]
    Count

  6. Number of thromboembolic events [ Time Frame: From start of treatment (week 0) to the end of the main part (week 24) ]
    Count

  7. Number of hypersensitivity type reactions [ Time Frame: From start of treatment (week 0) to the end of the main part (week 24) ]
    Count

  8. Number of injection site reactions [ Time Frame: From start of treatment (week 0) to the end of the main part (week 24) ]
    Count

  9. Number of patients with antibodies to concizumab [ Time Frame: From start of treatment (week 0) to the end of the main part (week 24) and end of trial (week 167) ]
    Count

  10. Concizumab plasma concentrations prior to the last prophylaxis dose administration in main part [ Time Frame: Week 24 ]
    ng/ml

  11. Peak thrombin generation prior to the last prophylaxis dose administration in main part [ Time Frame: Week 24 ]
    nM

  12. Free Tissue Factor Pathway Inhibitor (TFPI) concentration value prior to the last prophylaxis dose administration in main part [ Time Frame: Week 24 ]
    ng/ml

  13. Concizumab plasma concentration (maximum concentration, Cmax) [ Time Frame: From 0 to 24 hours where 0 is time of prophylaxis dose at week 24 ]
    ng/ml

  14. Concizumab plasma concentration area under the curve (AUC) [ Time Frame: From 0 to 24 hours where 0 is time of prophylaxis dose at week 24 ]
    ng*hr/ml


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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 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).

Exclusion Criteria:

  • Known or suspected hypersensitivity to monoclonal antibodies.
  • Known inherited or acquired coagulation disorder other than congenital haemophilia.
  • Ongoing or planned Immune Tolerance Induction treatment.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04083781


Locations
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Sponsors and Collaborators
Novo Nordisk A/S
Investigators
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Study Director: Clinical Reporting Anchor and Disclosure (1452) Novo Nordisk A/S
More Information
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Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT04083781    
Other Study ID Numbers: NN7415-4311
U1111-1225-9670 ( Other Identifier: World Health Organization (WHO) )
2018-004889-34 ( Registry Identifier: European Medicines Agency (EudraCT) )
First Posted: September 10, 2019    Key Record Dates
Last Update Posted: March 26, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
URL: http://novonordisk-trials.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hemophilia A
Hemophilia B
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
 Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked