The Efficacy and Safety of SerpinPC in Participants with Severe Hemophilia a or Moderately Severe to Severe Hemophilia B (PRESent-2)

A Global, Open-label, Adaptive Design Study to Investigate the Efficacy and Safety of SerpinPC in Subjects with Severe Hemophilia a or Moderately Severe to Severe Hemophilia B

The purpose of the study is to evaluate the efficacy, safety, tolerability and pharmacokinetics of prophylactic SerpinPC administered subcutaneously (SC) to participants with severe hemophilia A (HemA) (with or without inhibitors) or moderately severe to severe hemophilia B (HemB) (without inhibitors) as part of the SerpinPC registrational program.

This study consists of 3 parts: Part 1: dose-justification phase, Part 2: dose-confirmatory phase, Part 3: extension phase for participants who complete either Part 1 or Part 2.

This adaptive design study has a randomized dose-justification component to investigate the efficacy and safety of SerpinPC as a therapeutic option, principally for participants with HemB without inhibitors. SerpinPC has a novel mechanism of action compared with marketed treatments and those that are in development.

Study Overview

• Status: Terminated
• Conditions: Hemophilia B; Hemophilia a
• Intervention / Treatment: Drug: SerpinPC

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Armenia
  • Yerevan, Armenia, 14
    • Yeolyan Hematology and Oncology Center, MoH of Armenia CJSC
• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
• Belgium
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Saint-Luc
  • Brussels, Belgium, 1020
    • Queen Fabiola Children
• Canada
  • Hamilton, Canada, L8S 4K1
    • Hamilton Health Sciences Corporation
  • Toronto, Canada, M5B 1W8
    • Unity Health Toronto
  • Ontario
    • Hamilton, Ontario, Canada, L8S4K1
      • Hamilton Health Sciences Corporation
• France
  • Le Kremlin-Bicêtre, France, 94270
    • Hôpital Bicêtre
  • IDF
    • Paris, IDF, France, 75015
      • Hôpital Necker - Enfants Malades
  • Rhone
    • Lyon, Rhone, France, 69500
      • Hospices Civils de Lyon (HCL) - Hopital Femme-Mere-Enfant (HFME)
• Germany
  • Berlin, Germany, 10249
    • Klinik fur Angiologie Hamostaseologie Haus 12 A Gerinnungssprechstunde
  • Hesse
    • Frankfurt, Hesse, Germany, 60590
      • University Hospital Frankfurt
  • Sachsen
    • Dresden, Sachsen, Germany, 1307
      • Universitätsklinikum Carl Gustav Carus Dresden
• India
  • Maharashtra
    • Mumbai, Maharashtra, India, 400022
      • K J Somaiya Super Speciality Hospital & Research Centre
  • Punjab
    • Ludhiāna, Punjab, India, 141008
      • Christian Medical College & Hospital
• Italy
  • Florence, Italy, 50134
    • Azienda Ospedaliero-Universitaria Careggi
  • Torino, Italy, 10126
    • A.O.U Citt della Salute e della Scienza di Torino
  • Verona, Italy, 37126
    • Azienda Ospedaliera Universitaria Integrata Verona
  • MI
    • Milano, MI, Italy, 20122
      • Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
  • UD
    • Udine, UD, Italy, 33100
      • Presidio Ospedaliero Universitario S. Maria della Misericordia - ASUFC
• Poland
  • Podkarpackie
    • Rzeszów, Podkarpackie, Poland, 35-302
      • Korczowski Bartosz, Gabinet Lekarski
  • Woj. Dolnośląskie
    • Wrocław, Woj. Dolnośląskie, Poland, 50-367
      • Kl Hemat Now Krwi i Trans USK
• South Africa
  • Eastern Cape
    • Port Elizabeth, Eastern Cape, South Africa, 6001
      • Phoenix Pharma Pty Ltd
• Spain
  • Barcelona, Spain, 8035
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain
    • Hospital Universitario La Paz
  • Murcia, Spain, 30120
    • Hospital Clinico Universitario Virgen de La Arrixaca
  • Málaga, Spain, 29010
    • Hospital Regional Universitario de Malaga Hospital Carlos Haya - Hospital Materno-Infantil
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
• Taiwan
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Taipei City, Taiwan, 10004
    • National Taiwan University Hospital
• Turkey
  • Edirne, Turkey, 22030
    • Trakya University Haematology Clinic
  • Istanbul, Turkey, 34093
    • Istanbul University Oncology Institute
  • Samsun, Turkey, 55200
    • Ondokuz Mayis University Medical Faculty
  • İzmir, Turkey, 1000
    • Kocaeli Universitesi Tip Fakultesi
  • İzmir, Turkey, 35100
    • Ege University Hospital Internal Disease
  • İzmir, Turkey, 35100
    • Ege University Medical Faculty Pediatric Hospital
• United Kingdom
  • Birmingham, United Kingdom, B15 2GW
    • University Hospitals Birmingham NHS Foundation Trust
  • Cardiff, United Kingdom, CF14 4XW
    • University Hospital of Wales
  • Glasgow, United Kingdom, G4 0SF
    • Glasgow Royal Infirmary
  • London, United Kingdom, NW3 2QG
    • Royal Free London NHS Foundation Trust
  • London, United Kingdom, W2 1NY
    • Imperial College Healthcare NHS Trust
  • London, United Kingdom, E1 2AT
    • Barts and London School of Medicine and Dentistry
  • Southampton, United Kingdom, S016 6YD
    • Southampton General Hospital
  • Kent
    • Canterbury, Kent, United Kingdom, CT1 3NG
      • Kent Canterbury Hospital
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 9DU
      • Oxford University Hospital
  • Tyne and Wear
    • Newcastle Upon Tyne, Tyne and Wear, United Kingdom, NE1 4LP
      • Royal Victoria Infirmary
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045-7202
      • University of Colorado School of Medicine
  • Florida
    • Tampa, Florida, United States, 33612
      • University of South Florida
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Indiana Hemophilia and Thrombosis Center, Inc.
  • Iowa
    • Iowa City, Iowa, United States, 52246
      • University of Iowa Healthcare
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Medical Center
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • East Carolina univeristy
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Hershey Medical Center
    • Pittsburgh, Pennsylvania, United States, 15213
      • Hemophilia Center of Western Pennsylvania
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center at Houston-Gulf States HTC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male participants ≥12 and ≤65 years of age at the time of informed consent. Enrollment of adolescents (aged ≥12 to <18 years) will be deferred until at least 12 adult participants from each SerpinPC treatment regimen have completed at least 12 weeks of dosing in Part 1 and safety of SerpinPC has been assessed
2. Capable of providing written informed consent (adolescent assent and parental/guardian/legal representative consent when appropriate) for participation and having the opportunity to discuss the study with the investigator or delegate
3. Historically documented severe HemA (defined as factor VIII less than (<) 0.01 international unit (IU)/milliliter(mL) [<1%]), with or without inhibitors, or moderately severe to severe HemB (defined as factor IX ≤0.02 IU/mL [≤2%]), without inhibitors high titer inhibitor (high titer inhibitor defined as ≥5
4. Participant is currently included in a prophylaxis program. Fulfillment of this criterion will be based on investigator's judgment of adequate prophylaxis regimen OR participant is undergoing an on-demand treatment regimen and must have had greater than or equal to (≥) 6 documented acute bleeding episodes (spontaneous or traumatic) that required treatment during the 6 months before screening. Irrespective of the treatment program that the participant is currently undergoing, they must be willing to remain in the same program for the duration of the prospective observational period
5. Participants who are currently in a prophylaxis program must be willing to stop prophylaxis (including episodic prophylaxis for sporting events) before the first dose of SerpinPC
6. For Part 1: At least 12 weeks of prospective documentation of bleeding episodes in the AP-0105 non-interventional study before SerpinPC dosing, or willing to complete a 12-week observational period (at minimum) in AP-0102
7. For Part 2: At least 24 weeks of prospective documentation of bleeding episodes in the AP-0105 non-interventional study before SerpinPC dosing or willing to complete a 24-week observational period (at minimum) in AP-0102
8. No bleeding in the 7 days before baseline (the prospective observation period can be extended by 10 days if there is an ongoing active bleed)
9. D-dimer of less than or equal to (≤) 750 micrograms(μg)/Liter(L). In cases where there is a resolving bleed, the exclusion threshold is ≤1750 milligrams(mg)/L at Screening and Pre-dosing visits
10. Adequate hematologic function, defined as a platelet count of ≥100,000/microliters(μL) (≥100 × 109/L) and hemoglobin level of ≥10 grams(g)/deciliter(dL) (≥100 g/L or ≥6.206 millimols(mmol)/L) at Screening and Pre-dosing visits
11. Adequate hepatic function, defined as a total bilirubin level of ≤1.5*upper limit of normal (ULN) (excluding Gilbert syndrome) and aspartate aminotransferase and/or alanine aminotransferase of ≤3 × ULN at Screening and Pre-dosing visits; no clinical signs or known laboratory or radiographic evidence consistent with cirrhosis of the liver
12. Adequate renal function, defined as a serum creatinine level of ≤2.0*ULN at Screening and Pre-dosing visits
13. Able to use a diary to document bleeding events and medication usage
14. Sexually active participants with a partner who could become pregnant should agree to use effective contraception for the duration of the study effective contraceptive measures include condom with or without spermicide, a combination of male condom with either cap, diaphragm, or sponge with spermicide (double barrier methods), vasectomy, partner using stable contraceptive measures (combined [estrogen and progestogen-containing] hormonal contraception or progestogen-only hormonal contraception initiated 2 or more menstrual cycles prior to screening, intrauterine device [IUD], intrauterine hormone-releasing system [IUS], bilateral tubal ligation), and/or sexual abstinence.

Exclusion Criteria:

1. Known severe thrombophilia (defined as antithrombin deficiency and/or protein S deficiency and or protein C deficiency).
2. Participant with previous factor VIII or factor IX inhibitor who responded to immune tolerance induction and remains on prophylactic factor concentrate
3. Previous deep vein thrombosis, pulmonary embolism, myocardial infarction, or stroke
4. History of intolerance to SC injections
5. Uncontrolled hypertension (systolic blood pressure >160 millimeter of mercury (mm Hg); diastolic blood pressure >100 mm Hg)
6. Weight >150 kg OR body mass index >40 Kilograms(kg)/meter square (m2)
7. Has active cancer and/or requires therapy for cancer, except for basal cell carcinoma
8. Participation in another clinical trial (except for AP-0105) during the 30 days before Screening
9. Use of emicizumab in the 24 weeks before Baseline (Day 0)
10. Prior, ongoing, or planned treatment with gene therapy for hemophilia
11. Any major medical, psychological, or psychiatric condition that could cause the participant to be unsuitable for the study or could interfere with the interpretation of the study results
12. History of or other evidence of recent alcohol or drug abuse as determined by the investigator (in the 12 months before Screening)
13. Known human immunodeficiency virus (HIV) infection with CD4 count (or T-cell count) of <200 cells/μL within 24 weeks before Screening and Pre-dosing visits. Participants with HIV infection who have CD4 >200 and meet all other criteria are eligible
14. Current or planned treatment with anticoagulant or antiplatelet drugs
15. Is planning to donate/bank sperm during SerpinPC treatment AND within 30 days of last dose of SerpinPC
16. Any other significant conditions or comorbidities that, in the opinion of the investigator, would make the participant unsuitable for enrollment or could interfere with participation in or completion of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 - Cohort 1: SerpinPC; Participants will receive SerpinPC 1.2 mg/kg SC Injection QW for 24 weeks after a minimum of 12 weeks of a prospective observation period.	Drug: SerpinPC; Administered as SC injection.; Other Names: Activated Protein C (APC) inhibitor
Experimental: Part 1 - Cohort 2: SerpinPC; Participants will receive SerpinPC 1.2 mg/kg SC Injection Q2W for 24 weeks after a minimum of 12 weeks of a prospective observation period.	Drug: SerpinPC; Administered as SC injection.; Other Names: Activated Protein C (APC) inhibitor
Experimental: Part 1 - Cohort 3: SerpinPC; Participants will receive SerpinPC 1.2 mg/kg SC Injection Q4W for 24 weeks after a minimum of 12 weeks of a prospective observation period.	Drug: SerpinPC; Administered as SC injection.; Other Names: Activated Protein C (APC) inhibitor
Experimental: Part 2 - SerpinPC (Dose-confirmatory phase); After a minimum of 24 weeks of prospective observation, participants will receive SerpinPC at dose of 1.2 mg/kg Q2W for 24 weeks in Part 2, unless the Interim Analysis (IA) shows a greater benefit-risk profile with either the 1.2 mg/kg QW or Q4W treatment regimens.	Drug: SerpinPC; Administered as SC injection.; Other Names: Activated Protein C (APC) inhibitor
Experimental: Part 3 - SerpinPC (Extension phase); After completion of dosing in Part 1 or Part 2, participants will continue treatment with SerpinPC at the dose of SerpinPC selected for Part 2 in a 24-week extension phase (Part 3).	Drug: SerpinPC; Administered as SC injection.; Other Names: Activated Protein C (APC) inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Annualized Bleeding Rate (ABR) for Treated Bleeds up to Week 24	Up to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annualized Bleeding Rate (ABR) for Treated Bleeds Up to Week 48		Up to Week 48
Annualized Bleeding Rate (ABR) for Treated Spontaneous Bleeds		Up to Week 48
Annualized Bleeding Rate (ABR) for Treated Spontaneous Joint Bleeds		Up to Week 48
Total Coagulation Factor and/or Bypass Product Consumption During Parts 2 and 3		Up to Week 48
Pharmacokinetic Plasma Concentrations of SerpinPC		From Day 1 up to 24 weeks
Haemophilia-specific QoL Instrument for Adults (Haem-A-QoL) Physical Health scale in participants aged 17 to ≤65 years with hemophilia	The Haem-A-QoL instrument contains 44 items across 10 domains relevant to HRQoL in adults (physical health, feelings, view of participant's self, sports and leisure, work and school, dealing with hemophilia, treatment, future, family planning, partnership, and sexuality). Each item is rated on a 5-point scale (1=never, 2=rarely, 3=sometimes, 4=often, 5=all the time). Higher scores are indicative of greater impairment in HRQoL.	From Baseline up to 24 weeks
Number of Participants With Adverse Events (AEs)		From Baseline up to Week 48

Collaborators and Investigators

• Sponsor: ApcinteX Ltd
• Collaborators: Centessa Pharmaceuticals plc

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2023
• Primary Completion (Actual): November 14, 2024
• Study Completion (Actual): February 28, 2025

Study Registration Dates

• First Submitted: March 16, 2023
• First Submitted That Met QC Criteria: March 16, 2023
• First Posted (Actual): March 29, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 7, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Hemophilia; SerpinPC
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Genetic Diseases, X-Linked; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemophilia A; Hemophilia B; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Fibrinolytic Agents; Anticoagulants; Protein C
• Other Study ID Numbers: AP-0102; 2022-502880-39-00 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No