Concizumab for Hemophilia

(explorer8 Trial)

Not currently recruiting at 186 trial locations

Overseen By Novo Nordisk

Age: Any Age

Sex: Male

Trial Phase: Phase 3

Sponsor: Novo Nordisk A/S

Disqualifiers: Thromboembolic disease, Coagulation disorder, 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: 12

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how concizumab, an anti-TFPI monoclonal antibody, can help individuals with hemophilia A or B, a condition where blood doesn't clot properly, to prevent bleeding episodes. The trial includes two groups: one will begin taking concizumab immediately, while the other will continue their usual treatment and switch to concizumab after six months. This study targets males aged 12 and older with severe hemophilia A or B who currently manage their condition with on-demand or preventive treatments. Participants must inject themselves daily at home and visit the clinic regularly for check-ups. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are in the group that continues with normal medicine, you will keep taking your usual medication for the first 6 months before starting the study medicine.

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

Research has shown that concizumab is generally well-tolerated by people with hemophilia A or B. Studies have found it to be a safe treatment that effectively reduces bleeding. Testing has included both intravenous and subcutaneous injections, and it has maintained a good safety record, with few serious side effects reported.

Additionally, current data suggests no new safety concerns with long-term use. However, as with many newer treatments, information on long-term safety remains limited. Overall, concizumab appears to be a promising option for managing hemophilia, with a reassuring safety record so far. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Concizumab is unique because it targets a key regulator in the blood clotting process called tissue factor pathway inhibitor (TFPI). Unlike traditional treatments for hemophilia, which often involve infusions of clotting factors to prevent or control bleeding, concizumab offers a different approach by modulating the body's natural anticoagulant pathways. This innovative mechanism could potentially provide more consistent protection against bleeding episodes and reduce the need for frequent infusions. Researchers are excited about concizumab because it might offer a more convenient and effective option for patients with hemophilia, improving their quality of life.

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

Research shows that concizumab helps reduce bleeding in people with hemophilia A and B. In this trial, participants will join different arms, with some receiving concizumab prophylaxis. Studies found that those taking concizumab experienced fewer bleeding episodes than those who did not. This consistent reduction in bleeding makes it a promising treatment for hemophilia. Patients also reported a better quality of life while using concizumab. Overall, the treatment has proven both effective and safe. ^{1 4 5 6 7}

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 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.

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.

Congenital severe haemophilia A (FVIII below 1%) or B (FIX equal to or below 2%).

I am a male aged 12 or older.

Exclusion Criteria

You have had an allergic reaction or are at risk for an allergic reaction to the trial product or related products.

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

I have a history of blood clots or am currently being treated for them.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive concizumab prophylaxis or continue with their normal medicine for 6 months before switching to concizumab

6 months

Approximately 4-week intervals for the first 6-12 months

Long-term Treatment

Participants continue concizumab treatment with visits approximately every 8 weeks

Up to 6.5 years

Approximately 8-week intervals for the remainder of the study

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Concizumab

Trial Overview 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.

How Is the Trial Designed?

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

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

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 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 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, 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 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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2216455

Phase 3 Trial of Concizumab in Hemophilia with Inhibitors Overall, these factors result in poor outcomes for patients with hemophilia B with inhibitors. Concizumab is a monoclonal antibody to ...

2. 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 ...

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

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. sciencedirect.com sciencedirect.com/science/article/pii/S2475037925000299

Concizumab prophylaxis in people with hemophilia A or B ... Estimated treatment difference at week 24 between patients in arms 1 and 2 was −18.0 points (95% CI, −26.4 to −9.5) for Haemophilia Quality of Life ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37646676/

Phase 3 Trial of Concizumab in Hemophilia with Inhibitors Among patients with hemophilia A or B with inhibitors, the annualized bleeding rate was lower with concizumab prophylaxis than with no ...

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 ...