Concizumab for Hemophilia

(explorer7 Trial)

Recruiting at 174 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

134 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Concizumab for treating hemophilia?

Concizumab has been shown to help reduce bleeding episodes in people with hemophilia by blocking a protein that normally slows down blood clotting. In studies, it increased the body's ability to form clots, which is important for preventing excessive bleeding. ^{1 2 3 4 5}

How is the drug Concizumab unique for treating hemophilia?

Concizumab is unique because it is a monoclonal antibody that targets the tissue factor pathway inhibitor (TFPI), which helps restore normal blood clotting in hemophilia patients. Unlike traditional treatments that replace missing clotting factors, Concizumab is administered subcutaneously (under the skin) and works by inhibiting TFPI to promote clot formation, offering a novel approach to managing bleeding episodes. ^{1 3 5 6 7}

What is the purpose of this trial?

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.

Research Team

Clinical Reporting Anchor and Disclosure (1452)

Principal Investigator

Novo Nordisk A/S

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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, 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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Concizumab: First Approval. [2023]

2. England pubmed.ncbi.nlm.nih.gov

A randomized trial of safety, pharmacokinetics and pharmacodynamics of concizumab in people with hemophilia A. [2023]

3. New Zealand pubmed.ncbi.nlm.nih.gov

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

4. United States 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. [2019]

5. New Zealand 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. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Phase 3 Trial of Concizumab in Hemophilia with Inhibitors. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Safety and pharmacokinetics of anti-TFPI antibody (concizumab) in healthy volunteers and patients with hemophilia: a randomized first human dose trial. [2023]