Concizumab for Hemophilia

(explorer7 Trial)

Not currently recruiting at 207 trial locations

Age: Any Age

Sex: Male

Trial Phase: Phase 3

Sponsor: Novo Nordisk A/S

Must be taking: Bypassing agents

Disqualifiers: Hypersensitivity, Coagulation disorder, Thromboembolic disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 167 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how well a new medicine, concizumab (an anti-TFPI monoclonal antibody), can help people with hemophilia A or B who have inhibitors. These inhibitors make usual treatments less effective. The trial aims to determine if concizumab can prevent bleeding and is safe to use. Participants will either begin taking concizumab immediately or continue their usual treatment for six months before switching to concizumab. This trial may suit those managing hemophilia with on-demand or preventive treatments and who have recently used or need bypassing agents. Participants will self-administer daily injections with a pen-like device at home. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications. However, if you usually take medicine to prevent bleeds, you will start the study medicine right away. If you take medicine only when you have a bleed, you might continue your normal medicine for the first 6 months.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that concizumab is generally safe for people with hemophilia A and B. Studies have found that patients tolerate it well when administered either intravenously or as a subcutaneous injection. It has a good safety record, with serious side effects being rare.

Early results suggest it effectively reduces bleeding without major safety concerns. Recent data have revealed no new safety issues, although more information is needed about its long-term safety. Overall, concizumab has demonstrated safety for many patients, but additional data will help confirm this over time. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for hemophilia?

Unlike the standard treatments for hemophilia, which often involve regular infusions of clotting factors, concizumab offers a novel approach by targeting the tissue factor pathway inhibitor (TFPI). This mechanism helps promote clotting without directly replacing missing factors, potentially offering a more consistent and convenient management strategy. Moreover, concizumab is administered via a simple subcutaneous injection, making it easier and less invasive than traditional intravenous infusions. Researchers are excited about concizumab because it could improve the quality of life for patients by reducing bleeding episodes with a more straightforward treatment regimen.

What evidence suggests that concizumab might be an effective treatment for hemophilia?

Research has shown that concizumab reduces bleeding in people with hemophilia A and B. In this trial, participants will join different treatment arms, including those receiving concizumab prophylaxis. Studies have found that concizumab works well as a preventive treatment, stopping bleeds before they start. For people with hemophilia who have inhibitors (antibodies that make treatment less effective), concizumab successfully reduces the number of bleeding episodes. It has also proven safe for patients. Overall, concizumab is a promising option for managing bleeding in hemophilia, improving the quality of life for those affected. ^{1 4 6 7 8}

Who Is on the Research Team?

Clinical Reporting Anchor and Disclosure (1452)

Principal Investigator

Novo Nordisk A/S

Are You a Good Fit for This Trial?

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.

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.

I am a male aged 12 or older.

I have needed treatment with special blood clotting agents in the last 6 months.

Exclusion Criteria

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

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

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily concizumab injections under the skin, which they administer themselves at home. The treatment phase includes randomization into different groups, with some starting concizumab immediately and others after 6 months.

167 weeks

Visits every 4 weeks for the first 6-12 months, then every 8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including recording information in an electronic diary and possibly wearing an activity tracker.

4 weeks

Extension

Participants in the extension part receive daily concizumab injections, continuing the treatment regimen.

Up to 7 years or until the drug is available for purchase

What Are the Treatments Tested in This Trial?

Interventions

• Concizumab

Trial Overview

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.

How Is the Trial Designed?

Group I: Arm 4: Concizumab prophylaxis Experimental Treatment 1 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 prophylaxis Experimental Treatment 1 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 prophylaxis Experimental Treatment 1 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 prophylaxis Experimental Treatment 1 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.

Concizumab is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Alhemo for:

• Hemophilia A with inhibitors
• Hemophilia B with inhibitors

Approved in United States as Alhemo for:

• Hemophilia A with factor VIII inhibitors
• Hemophilia B with factor IX inhibitors

Approved in Canada as Alhemo for:

• Hemophilia A with inhibitors
• Hemophilia B with inhibitors

Who Is Running the Clinical Trial?

Novo Nordisk A/S

Lead Sponsor

Trials

1,578

Recruited

3,813,000+

Lars Fruergaard Jørgensen

Novo Nordisk A/S

Chief Executive Officer since 2017

MSc in Finance and Business Administration, Aarhus School of Business, Aarhus University, Denmark

Martin Holst Lange

Novo Nordisk A/S

Chief Medical Officer since 2021

MD from University of Copenhagen

Published Research Related to This Trial

Concizumab is a monoclonal antibody that effectively prevents tissue factor pathway inhibitor (TFPI) from inhibiting activated Factor X, which is crucial for blood clotting, making it a promising treatment for hemophilia A and B.

In March 2023, concizumab received approval in Canada for use in adolescents and adults with hemophilia B who have FIX inhibitors, marking a significant advancement in prophylactic treatment options to reduce bleeding episodes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concizumab: First Approval. Keam, SJ.[2023]

Concizumab effectively binds to and neutralizes the inhibitory function of tissue factor pathway inhibitor (TFPI), promoting coagulation, which could be beneficial for patients with hemophilia.

Pharmacokinetic studies in rabbits showed a non-linear, dose-dependent clearance profile for concizumab, indicating that its distribution and elimination are influenced by its interaction with TFPI on the endothelium of blood vessels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Target-mediated clearance and bio-distribution of a monoclonal antibody against the Kunitz-type protease inhibitor 2 domain of Tissue Factor Pathway Inhibitor. Hansen, L., Petersen, LC., Lauritzen, B., et al.[2019]

Concizumab, a monoclonal antibody that inhibits tissue factor pathway inhibitor (TFPI), effectively restores thrombin generation in hemophilia patients, showing promise in reducing bleeding episodes as demonstrated in both plasma studies and a rabbit model.

In Phase 1 trials, Concizumab led to a dose-dependent decrease in TFPI levels and increased thrombin generation without significant thrombosis risk, indicating its potential as a safe and effective alternative to traditional factor replacement therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of Tissue Factor Pathway Inhibitor (TFPI) as a Treatment for Haemophilia: Rationale with Focus on Concizumab. Chowdary, P.[2023]

Concizumab is a humanized monoclonal antibody that targets the Kunitz-2 domain of Tissue Factor Pathway Inhibitor (TFPI), showing promise in restoring thrombin generation and enhancing blood clotting in hemophilia patients.

Preclinical and clinical studies, including those from the EXPLORER program, support concizumab's potential as a new treatment option for hemophilia, with ongoing trials eagerly awaited for further results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concizumab as a Subcutaneous Prophylactic Treatment Option for Patients with Hemophilia A or B: A Review of the Evidence and Patient's Perspectives. Pasca, S.[2022]

In the explorer7 trial involving 133 patients with hemophilia A or B with inhibitors, concizumab prophylaxis significantly reduced the annualized bleeding rate to 1.7 episodes compared to 11.8 episodes in the no prophylaxis group, demonstrating its efficacy in preventing bleeding events.

After a treatment pause due to nonfatal thromboembolic events, no further thromboembolic incidents were reported once concizumab therapy resumed, indicating a favorable safety profile for the drug in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 3 Trial of Concizumab in Hemophilia with Inhibitors. Matsushita, T., Shapiro, A., Abraham, A., et al.[2023]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12078972/

Evaluating the Safety and Efficacy of Concizumab in ...

Concizumab appears to be an effective and safe prophylactic treatment for patients with hemophilia A and B, demonstrating consistent reductions in bleeding ...

2.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa2216455

Phase 3 Trial of Concizumab in Hemophilia with Inhibitors

Success rates with induction of immune tolerance among patients with hemophilia B with inhibitors remain low, and such therapy has potentially ...

3.

sciencedirect.com

sciencedirect.com/science/article/pii/S2352302624003077

Concizumab prophylaxis in people with haemophilia A or ...

Concizumab was effective in reducing the bleeding rate compared with no prophylaxis and was considered safe in patients with haemophilia A or B ...

4.

journals.lww.com

journals.lww.com/annals-of-medicine-and-surgery/fulltext/2025/10000/alhemo_s_fda_approval__a_new_treatment_option_for.89.aspx

Alhemo's FDA approval: a new treatment option for...

The new approval of Alhemo is considered to be a significant option for the better quality of life for patients by reducing the amount of ...

5.

tandfonline.com

tandfonline.com/doi/full/10.1080/17425255.2025.2524873?src=

Full article: Pharmacokinetic evaluation of concizumab for ...

Concizumab has an acceptable safe profile and efficacy in hemophilia A or B with and without inhibitors.

6.

sciencedirect.com

sciencedirect.com/science/article/pii/S1538783622089711

Safety and pharmacokinetics of anti‐TFPI antibody ...

Concizumab showed a favorable safety profile after iv or sc administration and nonlinear pharmacokinetics was observed due to target‐mediated clearance.

7.

ema.europa.eu

ema.europa.eu/en/medicines/human/EPAR/alhemo

Alhemo | European Medicines Agency (EMA)

People with haemophilia A or B are at risk of bleeding because they lack proteins that help the blood clot (factor VIII for haemophilia A and factor IX for ...

8.

thelancet.com

thelancet.com/journals/lanhae/article/PIIS2352-3026(24)00307-7/fulltext

Concizumab prophylaxis in people with haemophilia A or ...

Long-term safety data are scarce for non-factor therapies but, on the basis of the current data, there are no new safety findings to note. Anti- ...