SerpinPC for Hemophilia

(PRESent-6 Trial)

No longer recruiting at 37 trial locations

Overseen By Centessa Pharmaceuticals

Age: Any Age

Sex: Male

Trial Phase: Phase 3

Sponsor: ApcinteX Ltd

Must not be taking: Anticoagulants, Antiplatelets

Disqualifiers: Deep vein thrombosis, Pulmonary embolism, 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

Compensation: Varies

Number of Visits: Unknown

Duration: Long-term

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called SerpinPC to evaluate its efficacy and safety for individuals with hemophilia, a condition where blood doesn't clot properly. Participants will receive a regular injection of SerpinPC every two weeks. The study seeks men who have completed a previous SerpinPC trial and adhered to all trial protocols. Eligible candidates with hemophilia may consider participating. As a Phase 3 trial, this study represents the final step before FDA approval, providing an opportunity to contribute to a potentially groundbreaking treatment.

Do I have to stop taking my current medications?

The trial requires that you stop taking anticoagulant or antiplatelet drugs.

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

Research has shown that SerpinPC offers promising safety results for people with severe hemophilia. One study demonstrated that SerpinPC reduced bleeding without causing unexpected high levels of a blood clot marker called D-dimer, indicating the drug did not lead to harmful clotting. Another study found that SerpinPC was safe and well-tolerated over a long period, with most participants handling the treatment without major issues.

This treatment is currently in a Phase 3 trial, which typically indicates it has passed earlier safety tests, adding some confidence in its safety. However, individual responses can vary, so discussing any concerns with a healthcare professional is always advisable. ^{1 2 3 4 5}

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

Researchers are excited about SerpinPC for hemophilia because it offers a unique approach compared to traditional treatments like factor replacement therapies. Unlike these standard options that require frequent intravenous infusions, SerpinPC is administered via a subcutaneous injection every two weeks, making it potentially more convenient for patients. Additionally, SerpinPC works by inhibiting activated protein C, a different mechanism of action that could help reduce bleeding episodes more effectively or safely. This novel approach has the potential to simplify treatment regimens and improve quality of life for those with hemophilia.

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

Research has shown that SerpinPC, the treatment under study in this trial, yields promising results in reducing bleeding for people with severe hemophilia. In earlier studies, participants who received SerpinPC experienced fewer bleeding episodes. This treatment targets a specific protein that helps control bleeding. Early findings suggest that regular use of SerpinPC can prevent unexpected bleeding and manage active bleeds effectively. Overall, the evidence supports SerpinPC as a potentially effective treatment for controlling bleeding in hemophilia. ^{2 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for males aged 12-65 with Hemophilia who have already completed a SerpinPC clinical trial and were compliant. They must be able to give informed consent, or if underage, obtain parental/guardian consent.

Inclusion Criteria

Completed participation in a sponsored SerpinPC hemophilia clinical trial and demonstrated compliance with the study requirements, including diary entries

Capable of providing written informed consent, with adolescent assent and parent/guardian consent when appropriate

I am a male between 12 and 65 years old.

Exclusion Criteria

Participation in any interventional clinical trial other than SerpinPC trials

I have had a blood clot, heart attack, or stroke.

Presence of significant conditions or comorbidities that, in the investigator's opinion, would make the subject unsuitable for enrolment or could interfere with study participation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

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

Long-term

Bi-weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants continue to receive SerpinPC to observe long-term safety and efficacy

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• SerpinPC

Trial Overview The study aims to assess the long-term effects of SerpinPC on people with Hemophilia. It looks at how well it works (efficacy), its safety, how the body tolerates it (tolerability), and how the body processes it (pharmacokinetics).

How Is the Trial Designed?

Group I: SerpinPC Experimental Treatment 1 Intervention

Participants will receive SerpinPC 1.2 milligrams/kilograms (mg/kg) subcutaneous injection every 2 weeks (Q2W) once they have completed treatment in a SerpinPC parent study.

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

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 survey of 17 European countries, it was found that while 13 have regulations for reporting adverse vaccine reactions, only six have full-time professionals dedicated to vaccine safety, highlighting a significant gap in resources and expertise.

The study revealed that reporting systems for adverse events following immunization (AEFI) are inconsistent across countries, with many lacking standardized definitions and reporting forms specifically designed for vaccines, which complicates the assessment of vaccine safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccinovigilance in Europe--need for timeliness, standardization and resources. Lankinen, KS., Pastila, S., Kilpi, T., et al.[2015]

Recent strategies for treating hemophilia A and B focus on blocking natural anticoagulant proteins, such as serpins, to restore the balance between procoagulant and anticoagulant systems, which could reduce bleeding episodes.

Studies have shown that targeting specific serpins like antithrombin and modifying α1-antitrypsin can effectively rebalance coagulation in hemophilia, suggesting a promising new therapeutic approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serpins, New Therapeutic Targets for Hemophilia. Aymonnier, K., Kawecki, C., Arocas, V., et al.[2021]

The safety profile of medications can change after they are approved for public use, as new safety issues may arise that were not identified during clinical trials.

Regulatory agencies, like the FDA, actively monitor medication safety through various methods, including analyzing adverse experience reports and using large electronic databases to detect potential safety signals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring product safety in the postmarketing environment. Sharrar, RG., Dieck, GS.[2021]

In a study involving 63 children under 6 years with hemophilia B, treatment with nonacog alfa effectively controlled bleeding events, showing a median annualized bleeding rate (ABR) of 1.1 for those on prophylactic treatment, indicating its efficacy in preventing bleeds.

No new safety concerns were identified during the study, with only a few adverse drug reactions and events of special interest reported, supporting the safety of nonacog alfa in this young patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of nonacog alfa for the treatment of haemophilia B in children younger than 6 years of age in a routine clinical care setting: the EUREKIX registry study. Liesner, R., Andersson, NG., Frisk, T., et al.[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]

In a study of 15 hemophilia A patients with inhibitors undergoing low-dose immune tolerance induction (ITI) from 1999 to 2017, 33.3% achieved a complete response, indicating that low-dose ITI can be effective for some patients despite the challenges of inhibitor treatment.

The study highlights that while high-dose ITI is the standard approach, low-dose ITI may be a viable alternative for selected patients, especially in settings with limited resources.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose Immune Tolerance Induction in Hemophilia: A Single-Center Experience. Zulfikar, B., Koc, B., Ozdemir, N.[2020]

Engineered serpins that selectively inhibit activated protein C (APC) have been developed, showing promise in restoring blood clotting in hemophilia B mice by promoting thrombin generation and normalizing bleeding after injury.

This innovative approach targets the protein C anticoagulant system, demonstrating that it can effectively improve hemostasis in vivo, which could lead to new treatments for hemophilia that avoid the complications of traditional factor replacement therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design and characterization of an APC-specific serpin for the treatment of hemophilia. Polderdijk, SG., Adams, TE., Ivanciu, L., et al.[2021]

In 2012, Canada reported an adverse event following immunization (AEFI) rate of 10.1 per 100,000 population, showing a decline from 14.8 in 2005, indicating improved safety monitoring over time.

The majority of AEFI reports (94%-95%) were non-serious, primarily involving mild reactions such as site pain, rash, and fever, highlighting the overall good safety profile of vaccines administered in Canada.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Canadian Adverse Events Following Immunization Surveillance System (CAEFISS): Annual report for vaccines administered in 2012. Law, BJ., Laflèche, J., Ahmadipour, N., et al.[2023]

Out of 6.16 million doses of Hib conjugate vaccine administered in Jiangsu province from 2008 to 2013, the overall incidence of adverse events following immunization (AEFI) was 76.60 per 100,000 doses, indicating that HibCV is generally safe for children.

Common vaccine reactions, such as fever and swelling, occurred more frequently in boys and older children, while rare reactions like anaphylactic shock were reported but remained very low, highlighting the need for continued monitoring of severe allergic reactions post-vaccination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Evaluation of safety of haemophilus influenza type b(Hib) conjugate vaccine in postmarketing based on the immunization information management system]. Wang, Z., Ma, F., Zhang, J., et al.[2018]

A multicenter study involving nine patients with inherited protein C deficiency demonstrated that a purified plasma-derived protein C concentrate is both safe and effective, with 19 out of 23 treatment courses resulting in complete recovery without any long-term complications.

The treatment showed excellent safety during 914 infusions, with no abnormal bleeding reported, even at high doses and during surgical procedures, indicating a strong safety profile for this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of inherited protein C deficiency by replacement therapy with the French purified plasma-derived protein C concentrate (PROTEXEL). Dreyfus, M., Ladouzi, A., Chambost, H., et al.[2007]

In a severely protein C-deficient patient, the combination of prothrombin complex concentrates (PCC) and Warfarin effectively improved global anticoagulation and reduced recurrent purpura, demonstrating a clinical benefit where Warfarin alone was insufficient.

PCC infusion significantly increased levels of coagulation factors and protein C function, although some factors returned to baseline quickly, indicating that while PCC can restore coagulation, its effects on protein C levels are temporary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemostatic assessment of combined anticoagulant therapy using warfarin and prothrombin complex concentrates in a case of severe protein C deficiency. Ogiwara, K., Nogami, K., Mizumachi, K., et al.[2020]

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. 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 ...

3. 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 ...

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

Release Details Part 5 data from the Phase 2a study (AP-0101) showed a continued favorable safety and tolerability profile for SerpinPC, as well as sustained ...

5. rarediseaseadvisor.com rarediseaseadvisor.com/news/the-first-patient-dosed-with-serpinpc-present3-study/

The First Patient Dosed With SerpinPC in PRESent-3 Study The primary efficacy endpoint for the study is the rate of treated bleeds in the observation period compared to the first 24 weeks of receiving ...

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.