Recombinant Factor VIIa for Hemophilia

(SCOPE HIM Trial)

Recruiting at 16 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

19 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Coagulation Factor VIIa (Recombinant) for hemophilia?

Research shows that recombinant factor VIIa (rFVIIa, NovoSeven) is effective in treating bleeding episodes in hemophilia patients, especially those with inhibitors (antibodies that make standard treatments less effective). It has been used successfully in various bleeding disorders and is generally well tolerated, providing a valuable alternative to traditional blood products. ^{1 2 3 4 5}

Is recombinant Factor VIIa safe for humans?

Recombinant Factor VIIa (rFVIIa), also known as NovoSeven, has been studied for safety in various conditions, including trauma and congenital bleeding disorders. While detailed safety data is available from trials like the CONTROL trial, it is generally considered safe, though adverse events have been observed, especially in critical bleeding situations. ^{1 6 7 8 9}

What makes the drug Recombinant Factor VIIa unique for treating hemophilia?

Recombinant Factor VIIa (rFVIIa) is unique because it is a synthetic version of a natural protein that helps blood clot, and it is specifically designed for patients with hemophilia who have developed inhibitors (antibodies that block standard treatments). Unlike traditional blood products, it is made using DNA technology, reducing the risk of viral transmission and immune reactions. ^{2 3 4 10 11}

What is the purpose of this trial?

This is an interventional, prospective, international, multicenter, single-arm, Phase 3, and sequential efficacy and safety study in adolescents and adults with congenital hemophilia A or B with inhibitors to factor VIII (FVIII) or factor IX (FIX) undergoing elective major surgical procedures.

Research Team

Miguel ESCOBAR, MD

Principal Investigator

The University of Texas Health Science Center, Houston

Eligibility Criteria

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

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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 (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 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]

References

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

Evidence supporting the use of recombinant activated factor VII in congenital bleeding disorders. [2021]

2. 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]

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

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

4. England 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. [2023]

5. England 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. [2023]

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

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

7. Australia pubmed.ncbi.nlm.nih.gov

Recombinant activated factor VII in critical bleeding: experience from the Australian and New Zealand Haemostasis Register. [2016]

8. Serbia pubmed.ncbi.nlm.nih.gov

[Recombinant activated factor VII in the treatment of intractable non-surgical bleeding following major vascular procedures]. [2019]

9. 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]

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

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

11. India pubmed.ncbi.nlm.nih.gov

Successful use of recombinant factor VIIa in pelvic fracture haemorrhage. [2016]