SEVENFACT® for Hemophilia

Recruiting at 24 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety of SEVENFACT® (coagulation factor VIIa [recombinant]-jncw) for individuals with Hemophilia A or B who have inhibitors, proteins that hinder standard treatments. The goal is to assess how well SEVENFACT® controls bleeding in these individuals, regardless of their use of other preventive treatments. Participants should have a history of hemophilia with inhibitors and be able to track their treatment using an app or paper diary. As a Phase 4 trial, SEVENFACT® is already FDA-approved and has proven effective, and this research aims to understand its benefits for more patients.

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 is the safety track record for SEVENFACT®?

Research has shown that SEVENFACT is approved for treating bleeding in individuals with Hemophilia A or B who have inhibitors, indicating it has undergone extensive testing for safety. Previous studies indicate that SEVENFACT helps stop bleeding by forming clots at the bleeding site.

Data from these studies suggest that SEVENFACT is generally well-tolerated. Most reported side effects were mild, such as headaches and nausea, while severe side effects were rare. This information may reassure those considering joining this trial.

Since this treatment is in a Phase 4 trial, it has already received approval for use. This phase primarily focuses on confirming safety and effectiveness in a larger group. Earlier studies have shown the treatment to be relatively safe. However, discussing any concerns with a healthcare professional before joining a trial is always important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike other treatments for hemophilia A and B, SEVENFACT® is a recombinant coagulation factor VIIa, which is designed to help manage bleeding events in patients with inhibitors. Researchers are particularly excited about SEVENFACT® because it offers a targeted approach by directly addressing the clotting deficiency that these patients experience, potentially providing quicker and more effective bleeding control. Additionally, SEVENFACT® is administered as needed, which offers flexibility in dosing and can be tailored to the individual needs of the patient, making it a promising option for those who require personalized treatment strategies.

What is the effectiveness track record for SEVENFACT® in treating hemophilia?

Research has shown that SEVENFACT® effectively treats bleeding in people with Hemophilia A or B who have inhibitors. In clinical studies, SEVENFACT® stopped bleeding in 93% of cases, demonstrating strong results in managing these episodes. The treatment aids blood clotting, which is essential for stopping bleeds. SEVENFACT® is already approved for this use, highlighting its proven effectiveness. Participants in this trial will receive SEVENFACT® to further investigate its safety and tolerability with or without prophylactic therapies. ^{1 3 4 6 7}

Who Is on the Research Team?

Mark Reding, MD

Principal Investigator

University of Minnesota

Tammuella Chrisentery-Singleton, MD

Principal Investigator

American Thrombosis and Hemostasis Network

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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) 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]

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 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) 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]

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]

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]

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]

Citations

1. fda.gov fda.gov/media/70442/download

NovoSeven RT NovoSeven RT is recombinant human coagulation Factor VIIa (rFVIIa), intended for promoting hemostasis by activating the extrinsic pathway of the coagulation ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11283401/

Current status and future prospects of activated recombinant ... Current status and future prospects of activated recombinant coagulation factor VIIa, NovoSeven®, in the treatment of haemophilia and rare bleeding disorders.

3. reference.medscape.com reference.medscape.com/drug/novoseven-rt-sevenfact-factor-viia-recombinant-342155

NovoSeven RT, Sevenfact (Factor VIIa, recombinant) ... NovoSeven RT only: Bleeding episodes or surgery: 15-30 mcg/kg IV bolus q4-6hr until hemostasis achieved. Doses as low as 10 mcg/kg shown to be effective.

4. sevenfact.com sevenfact.com/Sevenfact_PI.pdf

HIGHLIGHTS OF PRESCRIBING INFORMATION ... Study 1: The safety of SEVENFACT has been evaluated in a safety and efficacy study of 27 subjects with Hemophilia A or B with inhibitors, which included ...

5. fda.gov fda.gov/media/70435/download

NovoSeven Coagulation Factor VIIa (Recombinant) Treatment was effective. (bleeding stopped or treatment was rated as effective by the physician) in 93% of episodes (90% for trial patients, 98% for published ...

6. novosevenrt.com novosevenrt.com/

NovoSeven® RT (coagulation Factor VIIa, recombinant) NovoSeven RT is designed with your safety in mind. It's the only rFVIIa used for breakthrough bleeds in the Hemlibra pivotal clinical trials.

7. hcp.sevenfact.com hcp.sevenfact.com/

For Healthcare Providers - SEVENFACT® SEVENFACT [coagulation factor VIIa (recombinant)-jncw] is indicated for the treatment and control of bleeding episodes occurring in adults and adolescents.