What side effects are associated with this type of intervention?

Common treatments for Hemophilia B, such as recombinant factor IX-albumin fusion (rFIX-FP) and glyco-PEGylated recombinant factor IX (rFIX-GP), are generally well-tolerated. Reported side effects include injection site reactions, headaches, and upper respiratory tract infections. In clinical trials, these treatments did not commonly lead to the development of inhibitors. Concizumab, an Anti-TFPI Monoclonal Antibody, is being studied for its efficacy and safety, with the primary focus on preventing bleeds and ensuring it is safe for long-term use.

What prior FDA approvals exist?

The FDA has approved several treatments for Hemophilia B, including recombinant factor IX products. Notable approvals include recombinant factor IX-albumin fusion (rFIX-FP; Idelvion) in 2016, which has a prolonged half-life of approximately 102 hours, and glyco-PEGylated recombinant factor IX (rFIX-GP; Rebinyn) in 2017, with a half-life of approximately 93 hours. These treatments are designed to prevent and manage bleeding episodes in individuals with Hemophilia B. While Concizumab, an anti-TFPI monoclonal antibody, is still under study, these recombinant factor IX products represent significant advancements in the management of Hemophilia B.

What other types of research exist?

Promising novel alternatives to Concizumab for Hemophilia B patients in 2024 include recombinant factor IX fusion proteins (e.g., rIX-FP) and glycoPEGylated recombinant factor IX (e.g., N9-GP). These therapies offer prolonged half-life and enhanced pharmacokinetic properties, making them effective options for prophylaxis and on-demand treatment.

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Monoclonal Antibodies

Concizumab for Hemophilia (explorer7 Trial)

Phase 3

Waitlist Available

Research Sponsored by Novo Nordisk A/S

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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)).

Must not have

Ongoing or planned Immune Tolerance Induction treatment.

Known inherited or acquired coagulation disorder other than congenital haemophilia.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 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)

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial tests concizumab, a new medicine, in people with hemophilia A or B who have inhibitors. It aims to see if concizumab can prevent bleeding by helping the blood clot more effectively. Concizumab has shown good results in earlier studies for hemophilia A and B.

Who is the study for?

This trial is for males aged 12 or older with Hemophilia A or B and inhibitors, who have used bypassing agents in the last 24 weeks. It's not for those with thromboembolic disease, high risk of blood clots, ongoing immune treatments, hypersensitivity to similar drugs, or other coagulation disorders.

What is being tested?

The study tests concizumab's effectiveness in preventing bleeds in people with hemophilia on-demand or prophylaxis treatment. Participants self-inject daily using a pen-injector and are monitored over six years with clinic visits and an electronic diary.

What are the potential side effects?

While specific side effects aren't listed here, participants will be closely monitored for any adverse reactions due to concizumab throughout the study period.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am a male aged 12 or older.

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I have Haemophilia A or B with a history of inhibitors.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am undergoing or planning to start treatment to boost my immune system.

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I have a blood clotting disorder that is not congenital haemophilia.

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I am currently being treated for or showing signs of blood clots.

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I have a history of blood clots, including in my heart, lungs, brain, or legs.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 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)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~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)

This trial's timeline: 3 weeks for screening, Varies for treatment, and 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) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

The number of treated spontaneous and traumatic bleeding episodes

Secondary study objectives

Area under the concizumab plasma concentration-time curve (AUC)

Change in 36 Item short form health survey version 2 (SF36v2) bodily pain

Change in SF36v2 physical functioning

+11 more

Side effects data

From 2020 Phase 2 trial • 36 Patients • NCT03196297

20%

Fibrin D dimer increased

20%

Prothrombin level increased

10%

Pyrexia

10%

Upper respiratory tract infection

10%

Thrombocytopenia

10%

Atypical pneumonia

10%

Arthralgia

10%

Hyperkeratosis

10%

Ligament sprain

10%

Lip discolouration

10%

Gastrointestinal haemorrhage

10%

Anal fistula

10%

Blood fibrinogen decreased

10%

Contusion

10%

Cough

10%

Dental caries

10%

Gingivitis

10%

Injection site haemorrhage

10%

Oropharyngeal pain

10%

Pharyngitis

100%

80%

60%

40%

20%

Study treatment Arm

Concizumab 0.25 mg/kg - Extension Part

Concizumab 0.20 mg/kg - Main Part

Concizumab 0.15 mg/kg - Extension Part

Concizumab 0.20 mg/kg - Extension Part

Concizumab 0.25 mg/kg - Main Part

Concizumab 0.15 mg/kg - Main Part

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

4Treatment groups

Experimental Treatment

Group I: Arm 4: Concizumab prophylaxisExperimental Treatment1 Intervention

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 2a (week 0).

Group II: Arm 3: Concizumab prophylaxisExperimental Treatment1 Intervention

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.

Group III: Arm 2: Concizumab prophylaxisExperimental Treatment1 Intervention

HAwI and HBwI patients, previously treated on-demand, will be randomised 1:2 to no prophylaxis versus concizumab prophylaxis.

Group IV: Arm 1: No prophylaxisExperimental Treatment1 Intervention

Haemophilia A with inhibitors (HAwI) and haemophilia B with inhibitors (HBwI) patients, previously treated on-demand, will be randomised 1:2 to no prophylaxis versus concizumab prophylaxis. In the extension part, patients in arm 1 will receive daily concizumab subcutaneous (s.c., under the skin) injections.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Concizumab

2023

Completed Phase 2

~110

0 / 6Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Hemophilia B include recombinant factor IX (rFIX) products, which replace the missing clotting factor IX, and factor IX-albumin fusion proteins, which extend the half-life of factor IX, reducing the frequency of infusions. Non-factor therapies, such as concizumab, an anti-TFPI monoclonal antibody, work by inhibiting tissue factor pathway inhibitor (TFPI), thereby enhancing thrombin generation and improving clot formation. These treatments are crucial for Hemophilia B patients as they help manage bleeding episodes and reduce the risk of complications. Concizumab, in particular, offers a promising alternative by potentially providing effective prophylaxis with subcutaneous administration, improving patient compliance and quality of life.

Non-factor therapies for bleeding disorders: A primer for the general haematologist.Administration of recombinant FVIIa (rFVIIa) to concizumab-dosed monkeys is safe, and concizumab does not affect the potency of rFVIIa in hemophilic rabbits.