What side effects are associated with this type of intervention?

Common treatments for Hemophilia A, such as Emicizumab and recombinant activated factor VII (rFVIIa), have known side effects. Emicizumab can cause injection site reactions, headache, and arthralgia, with serious risks including thrombotic events and thrombotic microangiopathy (TMA) when combined with activated prothrombin complex concentrate (aPCC). Recombinant activated factor VII (rFVIIa) is associated with thromboembolic events like deep vein thrombosis and myocardial infarction. Careful monitoring is essential to manage these risks.

What prior FDA approvals exist?

FDA-approved treatments for Hemophilia A include Emicizumab, a bispecific monoclonal antibody that mimics the function of factor VIII and is used for prophylaxis in patients with and without inhibitors. Emicizumab is administered subcutaneously and has shown significant efficacy in reducing bleeding rates. Another treatment is recombinant activated factor VII (rFVIIa), used for managing bleeding episodes in patients with inhibitors. While Concizumab, an anti-TFPI monoclonal antibody, is still under study, it aims to prevent bleeds by targeting tissue factor pathway inhibitor (TFPI), similar to how Emicizumab targets the coagulation pathway to prevent bleeding.

What other types of research exist?

Promising novel alternatives to Concizumab for Haemophilia A patients include Emicizumab, which has shown good efficacy and safety in both clinical trials and real-world studies. Other potential alternatives under investigation include gene therapies and newer monoclonal antibodies targeting different pathways involved in coagulation.

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Monoclonal Antibodies

Concizumab for Hemophilia (explorer8 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.

Must not have

Known inherited or acquired coagulation disorder other than congenital haemophilia.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up time frame is presented under 'outcome measure description'.

Awards & highlights

Pivotal Trial

No Placebo-Only Group

Summary

This trial tests concizumab, a new daily injectable medicine, in people with haemophilia A or B without inhibitors. The goal is to see if it can safely prevent bleeding episodes. Participants will either start the new medicine immediately or after a period of time, depending on their current treatment plan. Concizumab has shown significant reduction in bleeding rates in previous trials.

Who is the study for?

This trial is for males aged 12 or older with severe haemophilia A (FVIII below 1%) or B (FIX equal to or below 2%), without inhibitors. Participants must consent and be able to inject themselves daily with the study drug, concizumab. They cannot join if they have other coagulation disorders, a history of blood clots, are at high risk for clotting events, or are allergic to ingredients in the trial product.

What is being tested?

The effectiveness of concizumab in preventing bleeds in people with haemophilia A or B is being tested. Some participants will start on concizumab immediately while others will begin after six months; assignment is random. Those already on prophylaxis treatment will receive it from the start. The medicine is self-administered daily via a pen-injector.

What are the potential side effects?

Potential side effects of concizumab may include reactions at the injection site, increased risk of bleeding episodes due to its blood-thinning properties, and possible allergic reactions among those sensitive to its components.

Eligibility Criteria

Inclusion Criteria

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

Select...

I am a male aged 12 or older.

Exclusion Criteria

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

Select...

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

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ time frame is presented under 'outcome measure description'.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~time frame is presented under 'outcome measure description'.

This trial's timeline: 3 weeks for screening, Varies for treatment, and time frame is presented under 'outcome measure description'. for reporting.

Treatment Details

Study Objectives

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

Secondary study objectives

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

Hemophilia A

For haemophilia A patients without inhibitors: Number of treated spontaneous and traumatic target joint bleeds

+14 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

Pivotal Trial

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

No Placebo-Only Group

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

Trial Design

4Treatment groups

Experimental Treatment

Group I: Arm 4: Concizumab prophylaxisExperimental Treatment1 Intervention

Arm 4 will include patients previously on prophylaxis with factor products with a minimum of 24 weeks observation in NN7415-4322 (explorer 6) (at least 30 HA and 30 HB patients). In addition, arm 4 will also include: 1) Patients who were randomised to arms 1 and 2 before the treatment pause. 2) HA patients who were in NN7415-4255 (explorer 5) at the time of the treatment pause, and who have now completed explorer 5. 3) On demand patients included after arms 1 and 2 are closed.

Group II: Arm 3: Concizumab prophylaxisExperimental Treatment1 Intervention

The HA patients enrolled into the concizumab phase 2 trial NN7415-4255 (explorer 5) will be offered enrolment into this arm.

Group III: Arm 2: Concizumab prophylaxisExperimental Treatment1 Intervention

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

Group IV: Arm 1: No prophylaxis (PPX)Experimental Treatment1 Intervention

Haemophilia A (HA) and haemophilia B (HB) patients, previously treated on-demand, will be randomised 1:2 to no prophylaxis versus concizumab prophylaxis. In the extension phase, this group will receive treatment with concizumab.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Concizumab

2023

Completed Phase 2

~110

0 / 2Eligibility 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

Common treatments for Hemophilia A include factor VIII replacement therapy, emicizumab, and concizumab. Factor VIII replacement therapy involves infusing the missing clotting factor directly into the bloodstream, which helps to prevent and control bleeding episodes. Emicizumab is a bispecific monoclonal antibody that mimics the function of factor VIII by bridging activated factor IX and factor X, thereby promoting blood clotting. Concizumab, an anti-TFPI monoclonal antibody, works by inhibiting tissue factor pathway inhibitor (TFPI), which enhances thrombin generation and improves clot formation. These treatments are crucial for Hemophilia A patients as they help to reduce bleeding episodes, prevent joint damage, and improve overall quality of life.

A randomized trial of safety, pharmacokinetics and pharmacodynamics of concizumab in people with hemophilia A.Administration of recombinant FVIIa (rFVIIa) to concizumab-dosed monkeys is safe, and concizumab does not affect the potency of rFVIIa in hemophilic rabbits.