SEVENFACT® for Hemophilia

Recruiting at 23 trial locations

Overseen By Jessica Callis

Age: Any Age

Sex: Any

Trial Phase: Phase 4

Sponsor: American Thrombosis and Hemostasis Network

Must not be taking: Unapproved prophylactic drugs

Disqualifiers: Other hemostasis disorders, Rabbit allergy, others

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

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 4 years

55 Participants Needed

Trial Summary

What is the purpose of this trial?

Phase IV multi-center, US-centric, open-label, safety study enrolling participants with Hemophilia A or B with inhibitors, 12 years of age and older, who are either on long term prophylactic treatment (e.g., emicizumab) at risk of experiencing a breakthrough bleeding event (BE), or who are not on prophylactic treatment who may need to control a BE.

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 on a prophylactic treatment for bleeding that is not FDA-approved, you may not be eligible to participate.

What data supports the effectiveness of the drug SEVENFACT® for Hemophilia?

Recombinant factor VIIa (rFVIIa, NovoSeven) has been shown to be effective in treating bleeding in hemophilia patients with inhibitors, and it is generally well tolerated. It has been used successfully in various situations, including surgeries, and is considered a valuable treatment alternative for patients with certain bleeding disorders. ^{1 2 3 4 5}

Is SEVENFACT® (recombinant factor VIIa) safe for use in humans?

Recombinant factor VIIa (rFVIIa, also known as NovoSeven) has been used in over 6,500 patients with hemophilia or other bleeding disorders, with more than 180,000 doses administered by 2001. Clinical experience suggests it is generally safe, with a very low incidence of blood clots, and no side effects reported even with prolonged use. ^{1 3 6 7 8}

What makes the drug SEVENFACT® unique for treating hemophilia?

SEVENFACT® (recombinant factor VIIa) is unique because it is a recombinant product that bypasses the need for other clotting factors, making it effective for patients with inhibitors to traditional treatments. It is produced using DNA biotechnology, reducing the risk of viral transmission and antigenicity compared to blood-derived products. ^{1 2 4 5 9}

Research Team

Mark Reding, MD

Principal Investigator

University of Minnesota

Tammuella Chrisentery-Singleton, MD

Principal Investigator

American Thrombosis and Hemostasis Network

Eligibility Criteria

This trial is for individuals aged 12 and older with Hemophilia A or B who have inhibitors. Participants must understand the study, be able to use an app or diary for tracking bleeding events and medication usage, and not have other clotting disorders or conditions that could interfere with the study.

Inclusion Criteria

Be able to provide medical evidence through prior medical history of previous inhibitor levels

Be willing and able to use the ATHN mobile application or a paper diary to document BEs and medication usage

I have hemophilia A or B with inhibitors.

Exclusion Criteria

Have any life-threatening disease, or other disease or condition which, in the investigator's judgment, could pose a potential hazard to the patient or interfere with study participation or study outcome (e.g., a history of non responsiveness to bypassing products or thromboembolic disease)

You had a new medical device implanted in the last 6 months that is still being tested and not yet approved for use.

You have taken a new experimental drug within the past month.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive SEVENFACT® to treat bleeding episodes, with dosing at the discretion of the attending physician

Up to 4 years

Visits as needed for bleeding episodes

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 days after last dose

Treatment Details

Interventions

• coagulation factor VIIa [recombinant]-jncw

Trial Overview The trial is testing SEVENFACT®, a coagulation factor VIIa [recombinant]-jncw, in people with Hemophilia A or B experiencing breakthrough bleeding events. It's open-label and includes those on prophylactic treatment like emicizumab as well as those without it.

Participant Groups

Group I: Hemophilia A and B Cases Experimental Treatment 1 Intervention

SEVENFACT® has been approved for the treatment of bleeding events in individuals with hemophilia A or B with inhibitors. This study is intended to further investigate the safety and tolerability of SEVENFACT in participants with hemophilia A or B with inhibitors in the presence or absence of prophylactic therapies. Dosing will be at the discretion of the attending physician, and each participant will be supplied with the equivalent of nine 75 µg/kg doses, which aligns with the recommended dosing schedule as provided in SEVENFACT's United States Prescribing Information (USPI). In the event of a bleeding episode (BE), the participant will either self-administer the correct dose under the guidance of the treating investigator or the dose will be administered at a treatment facility.

coagulation factor VIIa [recombinant]-jncw is already approved in United States, European Union for the following indications:

Approved in United States as SEVENFACT for:

• Hemophilia A with inhibitors
• Hemophilia B with inhibitors

Approved in European Union as NovoSeven for:

• Hemophilia A with inhibitors
• Hemophilia B with inhibitors
• Congenital factor VII deficiency
• Glanzmann's thrombasthenia
• Acquired hemophilia

Approved in United States as NovoSeven for:

• Hemophilia A with inhibitors
• Hemophilia B with inhibitors
• Congenital factor VII deficiency
• Glanzmann's thrombasthenia
• Acquired hemophilia

Who Is Running the Clinical Trial?

American Thrombosis and Hemostasis Network

Lead Sponsor

Trials

11

Recruited

204,000+

LFB USA, Inc.

Industry Sponsor

Trials

3

Recruited

90+

Findings from Research

Recombinant factor VIIa (NovoSeven) effectively initiates coagulation in patients with inhibitors to clotting factors, demonstrating efficacy in various clinical situations, including surgeries, without causing systemic coagulation activation.

The treatment has a short half-life of 2 to 3 hours and is administered at dosages of 90-120 mcg/kg every 2-3 hours, but it has shown no side effects even with prolonged use, although its high cost may be a drawback.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Recombinant activated factor VII: a new treatment for hemophilia]. Goudemand, J.[2019]

NN1731, a recombinant activated factor VII analog, was found to be safe and well tolerated in a clinical trial involving healthy male subjects, with no serious adverse events or antibody formation reported at doses up to 30 microg kg(-1).

The pharmacokinetic profile of NN1731 demonstrated a two-compartment model with a rapid initial distribution phase (half-life of 20 minutes) followed by a slower elimination phase (half-life of 3 hours), indicating effective activity in coagulation-related parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the safety and pharmacokinetics of a fast-acting recombinant FVIIa analogue, NN1731, in healthy male subjects. Møss, J., Scharling, B., Ezban, M., et al.[2023]

NN1731, a modified version of recombinant factor VIIa, shows significantly enhanced ability to activate factor X and generate thrombin compared to standard rFVIIa, achieving this at 50-fold lower concentrations.

In both normal and fibrinolytic conditions, NN1731 not only promotes faster clotting but also improves the stability of the clot more effectively than rFVIIa, indicating its potential as a superior treatment for bleeding in hemophilia patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A variant of recombinant factor VIIa with enhanced procoagulant and antifibrinolytic activities in an in vitro model of hemophilia. Allen, GA., Persson, E., Campbell, RA., et al.[2017]

Recombinant factor VIIa (NovoSeven) is effective and generally well tolerated for treating bleeding episodes in patients with specific bleeding disorders, such as hemophilia A or B with inhibitors, and is a preferred treatment for hemophilia B with high-responding inhibitors.

This treatment is relatively safe, showing low risks of antigenicity, thrombogenicity, and viral transmission, making it a valuable alternative to traditional blood products in managing bleeding disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant factor VIIa (Eptacog Alfa): a review of its use in congenital or acquired haemophilia and other congenital bleeding disorders. Siddiqui, MA., Scott, LJ.[2018]

Recombinant factor VIIa (rFVIIa) was successfully used to stabilize a 63-year-old burn patient with severe coagulopathy, demonstrating its efficacy as a hemostatic agent in critical situations.

After administering rFVIIa, the patient achieved hemodynamic stability and improved hematocrit levels within 4 hours, indicating effective control of bleeding following extensive surgical procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant factor VIIa: hemostatic adjunct in the coagulopathic burn patient. Martin, JT., Alkhoury, F., McIntosh, BC., et al.[2021]

Recombinant activated coagulation factor VII (rFVIIa) is highly effective in treating bleeding episodes in pediatric patients with congenital hemophilia with inhibitors, achieving effectiveness in 95.4% of cases across various age groups.

The treatment is considered safe, with adverse reactions similar to those seen in adults, and only one confirmed thrombotic event related to rFVIIa, indicating a favorable safety profile for pediatric use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of recombinant factor VIIa by pediatric age cohort: reassessment of compassionate use and trial data supporting US label. Croteau, SE., Nakar, C., Neufeld, EJ., et al.[2018]

Recombinant factor VIIa (rFVIIa) has been safely administered to over 6,500 patients with hemophilia and other bleeding disorders, with more than 180,000 doses given by May 2001, showing its effectiveness in treating bleeding episodes.

The incidence of thrombotic events associated with rFVIIa is very low, and when they do occur, they are often linked to improvements in the body's ability to stop bleeding rather than a direct effect of the treatment itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant factor VIIa (Novoseven) and the safety of treatment. Roberts, HR.[2019]

In a large phase III study involving 560 actively hemorrhaging trauma patients, recombinant activated factor VII (rFVIIa) did not increase the overall risk of adverse events or mortality compared to placebo, indicating its safety in this critical setting.

While there was a slight imbalance in reported myocardial infarctions in the rFVIIa group, the use of rFVIIa was associated with a significantly lower rate of acute respiratory distress syndrome compared to the placebo group (3.0% vs. 7.2%), suggesting potential benefits in respiratory outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant activated factor VII safety in trauma patients: results from the CONTROL trial. Dutton, RP., Parr, M., Tortella, BJ., et al.[2020]

Recombinant factor VIIa (rFVIIa) is a safe and effective treatment for hemophiliacs with inhibitory antibodies, making it the only bypassing agent produced through recombinant technology.

The availability of rFVIIa has led to extensive clinical and biochemical research, enhancing our understanding of its mechanism of action and paving the way for improved variants currently in development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant coagulation factor VIIa--from molecular to clinical aspects of a versatile haemostatic agent. Persson, E., Bolt, G., Steenstrup, TD., et al.[2016]

References

1. France pubmed.ncbi.nlm.nih.gov

[Recombinant activated factor VII: a new treatment for hemophilia]. [2019]

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

Evaluation of the safety and pharmacokinetics of a fast-acting recombinant FVIIa analogue, NN1731, in healthy male subjects. [2023]

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

A variant of recombinant factor VIIa with enhanced procoagulant and antifibrinolytic activities in an in vitro model of hemophilia. [2017]

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

Recombinant factor VIIa (Eptacog Alfa): a review of its use in congenital or acquired haemophilia and other congenital bleeding disorders. [2018]

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

Recombinant factor VIIa: hemostatic adjunct in the coagulopathic burn patient. [2021]

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

Safety and efficacy of recombinant factor VIIa by pediatric age cohort: reassessment of compassionate use and trial data supporting US label. [2018]

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

Recombinant factor VIIa (Novoseven) and the safety of treatment. [2019]

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

Recombinant activated factor VII safety in trauma patients: results from the CONTROL trial. [2020]

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

Recombinant coagulation factor VIIa--from molecular to clinical aspects of a versatile haemostatic agent. [2016]