Recombinant Factor VIIa for Hemophilia

(SCOPE HIM Trial)

No longer recruiting at 21 trial locations

Overseen By Eric CARBONNELLE (for the only use of healthcare professionals)

Age: Any Age

Sex: Male

Trial Phase: Phase 3

Sponsor: Laboratoire français de Fractionnement et de Biotechnologies

Must not be taking: Immunosuppressants, NSAIDs, others

Disqualifiers: Coagulation disorders, Immunosuppression, 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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of a new treatment for individuals with hemophilia A or B who struggle with standard treatments. It targets those with inhibitors that block regular treatments and who plan to undergo major surgery. The trial uses Coagulation Factor VIIa (Recombinant) to manage bleeding during and after surgery. Individuals with congenital hemophilia A or B scheduled for elective major surgery might be suitable candidates for this trial. As a Phase 3 trial, this study is the final step before FDA approval, offering participants an opportunity to contribute to the potential availability of a new treatment option.

Will I have to stop taking my current medications?

The trial requires that you stop using aspirin, NSAIDs, herbs, natural medications, or other drugs with platelet inhibitory properties one week before surgery and during treatment. If you are using emicizumab, your dosing regimen must be stable and within the approved range.

Is there any evidence suggesting that Coagulation Factor VIIa (Recombinant) is likely to be safe for humans?

Research shows that Coagulation Factor VIIa (Recombinant), or rFVIIa, has helped people with hemophilia who have inhibitors—blockers to factor VIII or IX—for over 30 years. These factors are proteins that help blood clot. Studies have found this treatment to be over 90% effective in stopping bleeding episodes.

Regarding safety, rFVIIa is considered quite safe for hemophilia patients. It has been used widely without major safety concerns, even at high doses. The FDA has approved this treatment for managing bleeding episodes, indicating it is generally well-tolerated.

In summary, past studies and long-term use demonstrate that Coagulation Factor VIIa (Recombinant) is both effective and safe for managing bleeding in hemophilia patients with inhibitors. ^{1 2 3 4 5}

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

Recombinant Factor VIIa is unique because it offers a lab-made version of the coagulation factor that our bodies naturally produce to help with blood clotting. Unlike traditional treatments for hemophilia, which often involve plasma-derived products, this recombinant approach reduces the risk of infections and allergic reactions. Researchers are excited because this treatment could provide a safer and more consistent option for managing bleeding episodes in hemophilia patients.

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

Research shows that Coagulation Factor VIIa (Recombinant), administered to participants in this trial, works well for people with hemophilia who have inhibitors, especially during surgery. Studies have found that it successfully stops bleeding in 84% to 93% of patients within 12 hours. It aids blood clotting, crucial for controlling bleeding. The treatment is generally well tolerated and often used during surgeries to prevent excessive bleeding. Overall, strong evidence supports its effectiveness in managing bleeding for those with hemophilia. ^{1 2 5 6 7}

Who Is on the Research Team?

Miguel ESCOBAR, MD

Principal Investigator

The University of Texas Health Science Center, Houston

Are You a Good Fit for This Trial?

This trial is for males aged 12-65 with congenital hemophilia A or B who have inhibitors to factor VIII or IX and are scheduled for elective major surgery. They must not have other coagulation disorders, be immunosuppressed, allergic to rabbit proteins, on certain medications like emicizumab outside of specific parameters, or have had recent thromboembolic events.

Inclusion Criteria

I have a positive inhibitor test or am expected to not respond well to certain clotting factor treatments.

I am scheduled for a major surgery as outlined in the study.

I am a male diagnosed with hemophilia A or B, regardless of severity.

Exclusion Criteria

I am currently taking emicizumab following the prescribed dosing.

I haven't taken any experimental drugs recently.

Patients with known intolerance to LR769 or any of its excipients

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgical Procedure and Immediate Post-Operative Care

Participants undergo elective major surgical procedures and receive Coagulation Factor VIIa (Recombinant) to prevent excessive bleeding

1 week

In-patient hospital stay

Post-Operative Monitoring

Participants are monitored for hemostatic response and safety at 24 hours and 120 hours after surgery

1 week

Daily monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Coagulation Factor VIIa (Recombinant)

Trial Overview The study tests the safety and effectiveness of Coagulation Factor VIIa (Recombinant) in preventing excessive bleeding during major surgeries in patients with hemophilia A or B with inhibitors. It's an international Phase 3 trial where all participants receive the same treatment.

How Is the Trial Designed?

Group I: Coagulation Factor VIIa (Recombinant) Experimental Treatment 1 Intervention

Coagulation Factor VIIa (Recombinant) is already approved in European Union, United States for the following indications:

Approved in European Union as Novoseven for:

• Hemophilia A
• Hemophilia B
• Congenital factor VII deficiency
• Glanzmann thrombasthenia

Approved in United States as Novoseven RT for:

• Hemophilia A
• Hemophilia B
• Congenital factor VII deficiency
• Glanzmann thrombasthenia

Approved in United States as Sevenfact for:

• Hemophilia A
• Hemophilia B
• Congenital factor VII deficiency

Approved in European Union as Cevenfacta for:

• Hemophilia A
• Hemophilia B
• Congenital factor VII deficiency

Who Is Running the Clinical Trial?

Laboratoire français de Fractionnement et de Biotechnologies

Lead Sponsor

Trials

28

Recruited

4,000+

Published Research Related to This Trial

Recombinant factor VIIa, initially designed for treating hemophilia, has shown successful application in managing severe bleeding in a 30-year-old male patient with a pelvic fracture.

This case highlights the potential of recombinant factor VIIa as a novel hemostatic agent for trauma-related hemorrhage, suggesting its efficacy beyond its original intended use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful use of recombinant factor VIIa in pelvic fracture haemorrhage. Dhruva, KK., Joel, VD., Antony, S., et al.[2016]

In a phase III trial involving 72 hemophilic patients with inhibitors, vatreptacog alfa demonstrated similar efficacy to rFVIIa, achieving 93% effective bleeding control at 12 hours and showing superior results in secondary outcomes like the number of doses needed and sustained bleeding control after 24-48 hours.

Despite its efficacy, vatreptacog alfa raised concerns due to the development of anti-drug antibodies in 11% of patients, which could limit its overall benefit-risk profile compared to established treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant factor VIIa analog in the management of hemophilia with inhibitors: results from a multicenter, randomized, controlled trial of vatreptacog alfa. Lentz, SR., Ehrenforth, S., Karim, FA., 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]

The Haemostasis Registry reported on 694 cases of off-label use of recombinant activated factor VII (rFVIIa) for critical bleeding across various medical situations, with a notable 69% response rate to a single dose.

While the 28-day survival rate was 68%, the use of rFVIIa was associated with a 6% rate of adverse events, primarily thromboembolic complications in patients undergoing cardiac surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant activated factor VII in critical bleeding: experience from the Australian and New Zealand Haemostasis Register. Isbister, J., Phillips, L., Dunkley, S., et al.[2016]

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]

Vatreptacog alfa (NN1731) was well tolerated in a study involving 51 patients with hemophilia and inhibitors, showing a low frequency of adverse events and no reported immunogenic or thrombotic issues.

The treatment demonstrated a high efficacy rate, with 98% of acute joint bleeds controlled within 9 hours of administration, compared to a 90% efficacy rate for the standard treatment, recombinant FVIIa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant factor VIIa analog (vatreptacog alfa [activated]) for treatment of joint bleeds in hemophilia patients with inhibitors: a randomized controlled trial. de Paula, EV., Kavakli, K., Mahlangu, J., et al.[2023]

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 activated factor VII (rFVIIa) is used to treat hemophilic patients with inhibitors against coagulation factors, but the evidence supporting its efficacy is weak due to limited sample sizes and study variability across eight randomized controlled trials involving 256 patients.

The authors recommend that rFVIIa treatment should be tailored to the individual's thrombin generation ability rather than solely relying on weight, suggesting that tests like thromboelastography could enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence supporting the use of recombinant activated factor VII in congenital bleeding disorders. Johansson, PI., Ostrowski, SR.[2021]

In a study of 32 patients undergoing vascular surgery, the use of recombinant activated factor VII (rFVIIa) effectively controlled severe bleeding in 29 patients, demonstrating its potential as a haemostatic agent when conventional methods fail.

Despite its effectiveness, the use of rFVIIa is recommended cautiously due to the lack of randomized controlled trials confirming its safety and efficacy in vascular patients, along with its high cost of approximately $4080 for a 4.8 mg dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Recombinant activated factor VII in the treatment of intractable non-surgical bleeding following major vascular procedures]. Koncar, IB., Savić, N., Davidović, LB., et al.[2019]

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 (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]

Citations

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

Current status and future prospects of activated recombinant ... Randomised studies conducted in patients with CHwI have reported efficacy rates for rFVIIa (eptacog alpha) of 84%–93% within 12 h [33-37], 86%–88% within 24 h [ ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2475037924003650

Recombinant factor VIIa: new insights into the mechanism ... Using a severe murine tail vein bleeding model in antibody-induced hemophilia A mice, the most potent of these variants reduced blood loss by 91%, as compared ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/18345709/

Recombinant factor VIIa (eptacog alfa): a review of its use ... Studies have shown it to be effective and generally well tolerated when used intravenously to treat bleeding episodes or provide hemostatic cover during surgery ...

4. fda.gov fda.gov/media/70442/download

NovoSeven RT NovoSeven RT (Coagulation Factor VIIa [Recombinant]) is a coagulation factor indicated for: •. Treatment of bleeding episodes and peri-operative management ...

5. va.gov va.gov/formularyadvisor/DOC_PDF/MON_Factor_VIIa_recombinant_jncw_SEVENFACT_Monograph_Feb_2023.pdf

Factor VIIa (recombinant)-jncw (SEVENFACT®) Drug ... Recombinant activated factor VIIa (rFVIIa) binds to tissue factor activating factor X to XI conversion, thus allowing the coagulation cascade to continue.

6. tandfonline.com tandfonline.com/doi/full/10.1080/17474086.2023.2248385

Efficacy and safety evaluation of eptacog beta (coagulation ... Recombinant factor VIIa analog in the management of hemophilia with inhibitors: results from a multicenter, randomized, controlled trial of vatreptacog alfa.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC1994012/

Recombinant activated clotting factor VII (rFVIIa) in the ... rFVIIa has been a remarkably safe agent for hemophiliacs but with high dosages being advocated and older patients being given such doses outside a trial setting ...