SerpinPC for Hemophilia B

(PRESent-3 Trial)

No longer recruiting at 24 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called SerpinPC for people with Hemophilia B, a condition where blood doesn't clot properly, especially in those resistant to standard treatments (known as inhibitors). The researchers aim to evaluate the effectiveness, safety, and tolerability of SerpinPC. Participants with Hemophilia B who experience frequent bleeding episodes and are willing to pause their current preventive treatment may be suitable candidates. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in Hemophilia B treatment.

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.

Is there any evidence suggesting that SerpinPC is likely to be safe for humans?

Research has shown that SerpinPC is generally safe. Earlier research found that participants tolerated SerpinPC well, even after 52 weeks of use. Another study reported no serious safety issues. These findings suggest that SerpinPC is usually safe for people, but as with any treatment, monitoring for side effects is important. ^{1 2 3 4 5}

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

Unlike the standard treatments for Hemophilia B, which often involve regular infusions of clotting factor IX, SerpinPC offers a novel approach by targeting the protein antithrombin to enhance the body’s natural clotting process. This subcutaneous injection is not only easier to administer but also occurs every two weeks, which could mean fewer visits to the clinic compared to traditional therapies. Researchers are particularly excited about SerpinPC because it may provide a more convenient and potentially more effective treatment option, reducing the bleeding episodes and improving the quality of life for individuals with Hemophilia B.

What evidence suggests that SerpinPC might be an effective treatment for Hemophilia B?

Research has shown that SerpinPC, the investigational treatment in this trial, may help treat Hemophilia B. In earlier studies, SerpinPC reduced bleeding in people with severe hemophilia. The data indicates it can lower the number of bleeding episodes to about one per year, which is quite low. In this trial, SerpinPC is administered as a simple injection under the skin every two weeks. Early results also show it is generally safe and well-tolerated by patients. This makes SerpinPC a potential new option for those with Hemophilia B. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05789524

NCT05789524 | The Efficacy and Safety of SerpinPC in ...

The purpose of the study is to evaluate the efficacy, safety, tolerability and pharmacokinetics of prophylactic SerpinPC administered subcutaneously (SC) to ...

2.

investors.centessa.com

investors.centessa.com/news-releases/news-release-details/centessa-pharmaceuticals-announces-new-data-additional-52-weeks

Release Details

Part 5 data reinforces favorable safety and tolerability profile and long-term efficacy results for SerpinPC: Median all-bleed ABR of 1.0, ...

3.

ashpublications.org

ashpublications.org/blood/article/142/Supplement%201/2619/500147/Serpin-PC-in-Persons-with-Severe-Hemophilia-PwH

Serpin-PC in Persons with Severe Hemophilia (PwH)

The previously presented data from the completed parts of AP-0101 showed that administration of SerpinPC reduced bleeding in persons with severe ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12141901/

The preclinical profile of SerpinPC: a potential new treatment ...

SerpinPC was able to treat active bleeds in HA mice and prevented spontaneous internal bleeding when given prophylactically. SerpinPC treatment was not ...

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05789537

A Study of SerpinPC in Participants with Hemophilia B ...

The purpose of the study is to evaluate the efficacy, safety, tolerability and pharmacokinetic (PK) profile of prophylactic SerpinPC in participants with ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04073498

The Safety and Tolerability of SerpinPC in Healthy Men ...

Patient is unable to tolerate SerpinPC. Patient with clinically significant safety data in Part 5 as determined by the Safety Review Committee or Investigator.

7.

ashpublications.org

ashpublications.org/blood/article/140/Supplement%201/460/490454/Serpinpc-in-Persons-with-Severe-Hemophilia-PwH

Serpinpc in Persons with Severe Hemophilia (PwH)

Conclusions The results from Parts 1 and 2 suggest that SerpinPC was well-tolerated in subjects. Reduction in ABR in Part 2 provides preliminary ...