SerpinPC for Hemophilia B

(PRESent-3 Trial)

Recruiting at 21 trial locations

Overseen By Centessa Pharmaceuticals

Age: Any Age

Sex: Male

Trial Phase: Phase 2

Sponsor: ApcinteX Ltd

Must not be taking: Anticoagulants, Antiplatelets

Disqualifiers: Severe thrombophilia, Cancer, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 48 weeks

3 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the study is to evaluate the efficacy, safety, tolerability and pharmacokinetic (PK) profile of prophylactic SerpinPC in participants with Hemophilia B with inhibitors, as part of the SerpinPC registrational program.

Do I have to stop taking my current medications for the trial?

Yes, if you are currently in a prophylaxis program, you must stop prophylaxis before the first dose of SerpinPC. The protocol does not specify about other medications, but you cannot be on anticoagulant or antiplatelet drugs.

What data supports the idea that SerpinPC for Hemophilia B is an effective treatment?

The available research does not provide specific data on SerpinPC for Hemophilia B. Instead, it focuses on a different treatment, the recombinant factor IX Fc fusion protein, which has shown effectiveness. This treatment requires fewer injections, offers better bleeding control, and improves patient quality of life compared to standard treatments. It is also cost-effective and well-tolerated, with no development of inhibitors, which are substances that can make treatments less effective. ^{1 2 3 4 5}

What safety data exists for SerpinPC in treating Hemophilia B?

The provided research does not specifically mention SerpinPC or its safety data. However, it discusses the importance of safety surveillance in bleeding disorders and the challenges faced in pharmacovigilance. It highlights the need for long-term safety monitoring of coagulation factor products, including recombinant therapies, and mentions various surveillance systems and studies in place for hemophilia treatments. For specific safety data on SerpinPC, further targeted research or clinical trial results would be needed. ^{5 6 7 8 9}

Is the drug SerpinPC a promising treatment for Hemophilia B?

Yes, SerpinPC is a promising treatment for Hemophilia B because it can reduce the frequency of injections needed, improve bleeding control, and enhance the quality of life for patients. ^{1 2 10 11 12}

Eligibility Criteria

This trial is for males aged 12-65 with Hemophilia B and inhibitors, who haven't bled in the week before starting. They must have a history of frequent bleeding episodes and be willing to stop current prophylaxis treatments. Participants need normal platelet counts and hemoglobin levels, plus documented bleeding history or agree to an observation period.

Inclusion Criteria

I am willing to stop my current prophylaxis before starting SerpinPC.

You haven't had any bleeding in the week leading up to the start of the study, unless there is a current, ongoing bleed, in which case the observation period can be extended.

Your D-dimer blood test result should be less than or equal to 750 micrograms per liter, but if you have a resolving bleed, it should be less than or equal to 1750 micrograms per liter at certain visits.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Observational

Prospective observation period for all participants

12 weeks

Treatment

Participants receive SerpinPC 1.2 mg/kg subcutaneous injection every 2 weeks

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• SerpinPC

Trial Overview The study tests SerpinPC's effectiveness, safety, tolerability, and how it moves through the body when used as a preventive treatment in those with Hemophilia B with inhibitors. It aims to become part of the standard care for these patients.

Participant Groups

Group I: SerpinPC Experimental Treatment 1 Intervention

Participants will receive SerpinPC 1.2 milligrams/kilogram (mg/kg) subcutaneous (SC) injection every 2 weeks (Q2W) for 48 weeks after a prospective observation of 12 weeks for all participants, either in a prior non-interventional study (AP-0105\[NCT05605678\]) or as part of the ongoing study observational period.

Who Is Running the Clinical Trial?

ApcinteX Ltd

Lead Sponsor

Trials

5

Recruited

230+

Centessa Pharmaceuticals plc

Industry Sponsor

Trials

10

Recruited

370+

Findings from Research

The recombinant factor IX Fc fusion protein (rFIXFc) significantly reduces the frequency of injections needed for hemophilia B treatment, with a prolonged half-life of 82.1 hours, allowing for administration every 1 to 2 weeks.

In a study of 123 male patients, rFIXFc resulted in low annualized bleeding rates (3.0 for weekly prophylaxis and 1.4 for interval-adjusted prophylaxis), with 90.4% of bleeding episodes resolving after just one injection, and no inhibitors detected in participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 3 study of recombinant factor IX Fc fusion protein in hemophilia B. Powell, JS., Pasi, KJ., Ragni, MV., et al.[2022]

In a local experience with two children suffering from haemophilia B, using factor IX Fc fusion protein resulted in a personalized dosing schedule that was more cost-effective than standard treatments.

This approach led to fewer injections, better control of bleeding episodes, improved tolerability, and no development of inhibitors, highlighting its potential benefits in managing haemophilia B.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omani experience with the use of factor IX Fc fusion protein. Alzadjali, SI., Wali, Y.[2021]

After two years of prophylaxis with recombinant factor IX Fc fusion protein (rFIXFc), participants with severe hemophilia B reported a significant reduction in chronic pain and the number of activities affected by pain, indicating improved quality of life.

The study showed a 25% reduction in the number of affected activities of daily living (ADLs) after switching to rFIXFc, highlighting its positive impact on daily functioning despite the median health-related quality of life score remaining stable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant factor IX-Fc fusion protein in severe hemophilia B: Patient-reported outcomes and health-related quality of life. O'Donovan, M., Quinn, E., Johnston, K., et al.[2023]

Switching from standard half-life factor IX (SHL FIX) treatment to recombinant factor IX Fc fusion protein (rFIXFc) prophylaxis significantly reduced annualized bleeding rates (ABRs) from an average of 4.7 to 1.7, indicating improved clinical outcomes for patients with hemophilia B.

Patients who switched to rFIXFc experienced a reduction in injection frequency and factor consumption, with a mean decrease of 1.0 injections per week and a 27.7 IU/kg/week reduction in factor usage, suggesting a lower treatment burden and potential improvement in quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Effectiveness of rFIXFc Prophylaxis in Patients with Haemophilia B Switched from Standard Half-Life Therapy in Three European Countries. Funding, E., Lowe, G., Poulsen, LH., et al.[2023]

The phase 3b extension study demonstrated that the recombinant fusion protein rIX-FP is safe and effective for long-term prophylaxis in pediatric patients with hemophilia B, with very low annualized spontaneous bleeding rates (median AsBR of 0.0 for 7- and 10-day regimens).

Patients were able to safely extend their prophylaxis intervals to every 10 or 14 days while maintaining effective bleed protection, with 96% of bleeding episodes successfully treated with just one or two injections of rIX-FP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Safety and Efficacy of Recombinant Coagulation Factor IX Albumin Fusion Protein (rIX-FP) in Previously Treated Pediatric Patients with Hemophilia B: Results from a Phase 3b Extension Study. Kenet, G., Chambost, H., Male, C., et al.[2020]

Safety surveillance studies are crucial for monitoring the safety of new biological therapies for bleeding disorders, particularly in tracking potential new infectious agents and the development of inhibitors in hemophilia treatment.

The European Haemophilia Safety Surveillance (EUHASS) project aims to establish long-term monitoring of coagulation factor products, addressing challenges like patient recruitment and disease severity assessment through national and international registries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current challenges of pharmacovigilance in bleeding disorders: converting the burden to benefit. Lassila, R., Armstrong, E.[2013]

In a study of 64 patients with hemophilia B who used recombinant factor IX fusion protein (rFIXFc) for an average of 2.7 years, 81% of those who switched from other treatments were able to lengthen their dosing intervals, indicating improved treatment flexibility.

Patients on rFIXFc prophylaxis experienced about a 50% reduction in weekly factor consumption and significant decreases in annualized bleed rates, demonstrating enhanced bleed control and treatment compliance in a real-world clinical setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world data demonstrate improved bleed control and extended dosing intervals for patients with haemophilia B after switching to recombinant factor IX Fc fusion protein (rFIXFc) for up to 5 years. Shapiro, A., Chaudhury, A., Wang, M., et al.[2021]

A long-term cohort study in France, initiated in 1994, monitored the safety of haemophilia treatments using plasma-derived and recombinant clotting factor products, involving 1234 patients across 39 centers.

With a median follow-up of 26.9 months and a total of 2729 patient-years, the study demonstrated good compliance with health surveillance, ensuring that any potential safety issues can be quickly investigated with centralized data and biological samples.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The French haemophilia cohort: rationale and organization of a long-term national pharmacosurveillance system. Calvez, T., Biou, M., Costagliola, D., et al.[2019]

In a phase I trial involving patients with hemophilia B, the recombinant fusion protein rIX-FP was found to be well tolerated with no serious adverse events, indicating a good safety profile for this new treatment.

rIX-FP demonstrated significantly improved pharmacokinetics, including a 5-fold increase in half-life and the ability to maintain therapeutic levels for up to 14 days, suggesting that it could allow for less frequent dosing compared to standard FIX therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PROLONG-9FP clinical development program--phase I results of recombinant fusion protein linking coagulation factor IX with recombinant albumin (rIX-FP). Santagostino, E.[2013]

In a study of 81 male patients with hemophilia B who switched to the extended half-life factor IX fusion protein (rIX-FP), there was a significant reduction in FIX consumption, with an average of 44.2 IU/kg/week for rIX-FP compared to 82.3 IU/kg/week for prior therapies.

Patients experienced a dramatic decrease in annualized bleeding rates, from an average of 2.6 bleeds per year with previous treatments to just 0.3 bleeds per year on rIX-FP, and the percentage of patients with zero bleeds increased from 24% to 81%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing bleeding rates, related clinical impact and factor utilization in German hemophilia B patients treated with extended half-life rIX-FP compared to prior drug therapy. Oldenburg, J., Yan, S., Maro, G., et al.[2020]

A new treatment for haemophilia B, called rIX-FP, is a genetically engineered fusion of recombinant factor IX and albumin, which significantly improves the drug's effectiveness and reduces the need for frequent infusions due to its longer-lasting effects in the body.

In animal studies, rIX-FP demonstrated a 10- to 30-fold increase in clotting activity compared to traditional treatments and effectively corrected bleeding in models of haemophilia B, indicating its potential as a promising therapy for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Half-life extension through albumin fusion technologies. Schulte, S.[2010]

The study introduces recombinant factor IX (rFIX) albumin fusion proteins with cleavable linkers, which significantly enhance the clotting activity of FIX, showing a 10- to 30-fold increase compared to non-cleavable linkers.

In animal models, these rIX-FPs demonstrated improved pharmacokinetic properties, including increased half-life and efficacy in reducing bleeding time, suggesting they could lead to less frequent dosing for patients with severe haemophilia B.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic fusion to albumin improves the pharmacokinetic properties of factor IX. Metzner, HJ., Weimer, T., Kronthaler, U., et al.[2009]

References

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

Phase 3 study of recombinant factor IX Fc fusion protein in hemophilia B. [2022]

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

Omani experience with the use of factor IX Fc fusion protein. [2021]

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

Recombinant factor IX-Fc fusion protein in severe hemophilia B: Patient-reported outcomes and health-related quality of life. [2023]

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

Real-World Effectiveness of rFIXFc Prophylaxis in Patients with Haemophilia B Switched from Standard Half-Life Therapy in Three European Countries. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Long-Term Safety and Efficacy of Recombinant Coagulation Factor IX Albumin Fusion Protein (rIX-FP) in Previously Treated Pediatric Patients with Hemophilia B: Results from a Phase 3b Extension Study. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Current challenges of pharmacovigilance in bleeding disorders: converting the burden to benefit. [2013]

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

Real-world data demonstrate improved bleed control and extended dosing intervals for patients with haemophilia B after switching to recombinant factor IX Fc fusion protein (rFIXFc) for up to 5 years. [2021]

8. England pubmed.ncbi.nlm.nih.gov

The French haemophilia cohort: rationale and organization of a long-term national pharmacosurveillance system. [2019]

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

PROLONG-9FP clinical development program--phase I results of recombinant fusion protein linking coagulation factor IX with recombinant albumin (rIX-FP). [2013]

10. England pubmed.ncbi.nlm.nih.gov

Assessing bleeding rates, related clinical impact and factor utilization in German hemophilia B patients treated with extended half-life rIX-FP compared to prior drug therapy. [2020]

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

Half-life extension through albumin fusion technologies. [2010]

12. Germany pubmed.ncbi.nlm.nih.gov

Genetic fusion to albumin improves the pharmacokinetic properties of factor IX. [2009]