Concizumab for Hemophilia A and B

(Explorer10 Trial)

Not currently recruiting at 167 trial locations

Overseen By Novo Nordisk

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Novo Nordisk A/S

Must be taking: Coagulation factors

Disqualifiers: Thromboembolic disease, Coagulation disorders, 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: Unknown

Duration: At least 32 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new medicine, concizumab (an Anti-TFPI monoclonal antibody), to determine its effectiveness in preventing bleeds and its safety for people with hemophilia A or B, regardless of the presence of inhibitors (substances that interfere with standard treatment). Participants will inject the medicine under their skin daily using a pen-injector. The trial is open to males with severe hemophilia A or B who experience frequent bleeds or are already using concizumab through compassionate use. 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 information does not specify if you need to stop taking your current medications. It is best to discuss this with the study team or your doctor.

Is there any evidence suggesting that concizumab is likely to be safe for humans?

Research shows that concizumab holds promise for treating hemophilia A and B. Studies have found it generally safe and effective in reducing bleeding episodes for people with these conditions. Concizumab is administered through injections under the skin, and results suggest it is well-tolerated, with no major new safety concerns reported.

In some studies involving people with hemophilia who have inhibitors (meaning their bodies don't respond to regular treatments), concizumab still demonstrated good safety results. This indicates that even in more complex cases, the treatment does not cause significant safety issues.

Overall, current evidence supports the safety of concizumab, though long-term safety information remains limited. Participants considering joining a trial should feel reassured by these findings but should always discuss any concerns with healthcare providers. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for hemophilia?

Concizumab is unique because it targets a specific protein in the blood called tissue factor pathway inhibitor (TFPI), which plays a crucial role in regulating blood clotting. Unlike standard treatments for hemophilia A and B, which typically involve factor replacement therapies to compensate for missing or deficient clotting factors, Concizumab offers a non-factor approach. This innovative mechanism can potentially reduce bleeding episodes and the need for frequent infusions, making it a promising option for patients. Researchers are excited about Concizumab because it could simplify treatment regimens and improve quality of life for those with hemophilia.

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

Studies have shown that concizumab effectively treats people with hemophilia A or B by consistently reducing bleeding, resulting in fewer bleeding episodes. Research indicates that concizumab is safe and serves as a good alternative to having no preventative treatment. In this trial, some participants will be concizumab-naïve, while others will have previously received concizumab through compassionate use. Patients, regardless of the presence of inhibitors (substances that can stop treatments from working), have benefited from this medication. Overall, concizumab is a promising option for managing hemophilia, lowering the chances of bleeding, and improving quality of life. ^{1 4 6 7 8}

Who Is on the Research Team?

Clinical Transparency (dept. 2834)

Principal Investigator

Novo Nordisk A/S

Are You a Good Fit for This Trial?

This trial is for individuals with severe haemophilia A or moderate/severe haemophilia B, with or without inhibitors. Participants must have a history of treatment for at least 26 weeks in the past year and give informed consent. It's not open to those allergic to concizumab, undergoing Immune Tolerance Induction, with thromboembolic disease or risk factors for it, other coagulation disorders besides haemophilia, or a history of thrombosis.

Inclusion Criteria

I have severe haemophilia A, moderate/severe haemophilia B, or haemophilia with inhibitors.

I have haemophilia A or B without inhibitors.

I have been on preventive treatment for at least 26 weeks in the past year.

Exclusion Criteria

I am undergoing or will undergo immune tolerance therapy.

I have had blood clots in the past.

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 injections of concizumab under the skin with a pen-injector

At least 32 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants may continue treatment until the study medicine is available for purchase in their country

Up to 4 years

What Are the Treatments Tested in This Trial?

Interventions

• Concizumab

Trial Overview The study tests concizumab's effectiveness in preventing bleeding episodes in people with haemophilia A/B. Participants will self-inject concizumab daily using a pen-injector. The trial spans 2-4 years depending on when the drug becomes commercially available.

How Is the Trial Designed?

Group I: Patients coming from compassionate use Experimental Treatment 1 Intervention

Patients previously treated with concizumab via compassionate use, either on an individual patient basis or through the concizumab compassionate use programme NN7415-4807

Group II: Concizumab-naïve patients Experimental Treatment 1 Intervention

Concizumab-naïve participants below 12 years of age at the time of consent/assent

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]

mAb 2021, a high-affinity monoclonal antibody targeting tissue factor pathway inhibitor (TFPI), effectively enhances clot formation in hemophilia by preventing TFPI's inhibition of the coagulation pathway, as demonstrated in both blood and plasma samples.

In a rabbit model of hemophilia, mAb 2021 significantly reduced bleeding for at least 7 days after a single intravenous dose, showing comparable efficacy to standard treatments like rFVIIa, suggesting it could be a promising new treatment option for hemophilia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemostatic effect of a monoclonal antibody mAb 2021 blocking the interaction between FXa and TFPI in a rabbit hemophilia model. Hilden, I., Lauritzen, B., Sørensen, BB., et al.[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]

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]

Concizumab, an anti-tissue factor monoclonal antibody, enhances thrombin generation in hemophilia A/B patients, and its effects are concentration-dependent, indicating its potential efficacy in improving hemostasis during prophylaxis.

When combined with bypassing agents like rFVIIa, APCC, or factor replacement therapies like rFVIII and rFIX, concizumab further increases thrombin generation, but the interactions are mostly additive rather than synergistic, suggesting careful dose adjustments are needed to ensure safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thrombin generation potential in the presence of concizumab and rFVIIa, APCC, rFVIII, or rFIX: In vitro and ex vivo analyses. Kjalke, M., Kjelgaard-Hansen, M., Andersen, S., 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. 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 ...

3. 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 ...

4. 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 ...

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- ...