A Study of SerpinPC in Participants with Hemophilia B (HemB) with Inhibitors

NCT05789537 | Terminated Phase 2 DMC FDA Drug

• 2 other identifiers: AP-01032022-502881-25-00
• Study Type: interventional
• Target: 3
• Locations: 11 countries
• Sites: 20

Brief Summary

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.

Conditions

Hemophilia B with Inhibitor; Hemophilia B

Keywords

SerpinPC; Hemophilia

Outcome Measures

Primary Outcomes (1)

• Annualized Bleeding Rate (ABR) for Treated Bleeds up to Week 24

  Up to Week 24

Secondary Outcomes (9)

• 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 SerpinPC Treatment

  Up to Week 48

• Pharmacokinetic Concentrations of SerpinPC

  From Day 1(Pre-dose) up to Week 48(Post-dose)

Study Arms (1)

SerpinPC

EXPERIMENTAL

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.

Drug: SerpinPC

Interventions

SerpinPC DRUG

Administered as SC injection.

Also known as: Activated Protein C (APC) inhibitor

SerpinPC

Eligibility Criteria

• Age: 12 Years - 65 Years
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male participants greater than or equal to (\>=) 12 and less than or equal to (\<=) 65 years of age at the time of informed consent.
• 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.
• Historically documented HemB (defined as factor IX \<=0.05 international unit/Milliliter (IU/mL) \[\<=5 percent (%)\]).
• 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.
• Historical or ongoing Factor IX inhibitor with bypass agents based on medical records or laboratory reports.
• Documented ABR of 6 in the 12 months before screening (participants not on prophylaxis regimen) or documented ABR of ≥2 for participants on prophylaxis regimen
• At least 12 weeks of prospective documentation of bleeding episodes in the AP-0105 (NCT05605678) non-interventional study before SerpinPC dosing, or willing to complete a 12-week observational period (at minimum) in AP-0103.
• 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).
• Adequate hematologic function, defined as a platelet count of \>=100,000/microliters (mcL) (\>=100\*10\^9/L) and hemoglobin level of \>=10 grams/deciliter(g/dL) (\>=100 g/L or \>= 6.206 millimoles per liter (mmol/L) at Screening and Pre-dosing visits.
• 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.
• Adequate renal function, defined as a serum creatinine level of \<=2.0\*ULN at Screening and Pre-dosing visits.
• Able to use a diary to document bleeding events and medication usage.
• Sexually active participants with a partner who could become pregnant should agree to use effective contraception for the duration of the study.
• Effective contraceptive measure 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.

You may not qualify if:

• Known severe thrombophilia (defined as antithrombin deficiency and/or protein S deficiency and/or protein C deficiency).
• Participant with previous factor IX inhibitor who responded to immune tolerance induction and remains on prophylactic factor concentrate.
• Previous deep vein thrombosis, pulmonary embolism, myocardial infarction, or stroke.
• History of intolerance to SC injections.
• Uncontrolled hypertension (systolic blood pressure \>160 millimeter of mercury (mm Hg); diastolic blood pressure \>100 mm Hg).
• Weight \>150 kilograms (kg) OR body mass index \>40 kg/meter square (m\^2).
• Has active cancer and/or requires therapy for cancer, except for basal cell carcinoma.
• Participation in another clinical trial (except for AP-0105 \[NCT05605678\]) during the 30 days before screening.
• Prior, ongoing, or planned treatment with gene therapy for HemB
• 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.
• History of or other evidence of recent alcohol or drug abuse as determined by the Investigator (in the 12 months before screening).
• Known human immunodeficiency virus (HIV) infection with CD4 count (or T-cell count) of \<200 cells/mcL within 24 weeks before Screening and Pre-dosing visits. Patients with HIV infection who have CD4 \> 200 and meet all other criteria are eligible.
• Current or planned treatment with anticoagulant or antiplatelet drugs
• Is planning to donate/bank sperm during SerpinPC treatment AND within 30 days of last dose of SerpinPC.
• 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.

Sponsors & Collaborators

• ApcinteX Ltd: lead
• Centessa Pharmaceuticals plc: collaborator

Study Sites (20)

University of Colorado School of Medicine

Aurora, Colorado, 80045-7202, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

East Carolina University

Greenville, North Carolina, 27834, United States

Location

Centre of Haematology named after prof. R. O. Yeolian/ Hemophilia center

Yerevan, 0014, Armenia

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Hopital Bicetre

Le Kremlin-Bicêtre, 94270, France

Location

CHRU de Lille Centre de biologie et pathologie

Lille, 59000, France

Location

Hospices Civils de Lyon (HCL) - Hopital Femme-Mere-Enfant (HFME)

Lyon, 69500, France

Location

Hopital Necker - Enfants Malades

Paris, 75015, France

Location

University Hospital Frankfurt M

Frankfurt, 60596, Germany

Location

K J Somaiya Super Speciality Hospital & Research Centre

Mumbai, Maharashtra, 400022, India

Location

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Chung Shan Medical University

Taichung, 40201, Taiwan

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 407, Taiwan

Location

Istanbul University Oncology Institute

Istanbul, 34093, Turkey (Türkiye)

Location

Ege University Medical Faculty Hospital

Izmir, 35100, Turkey (Türkiye)

Location

Nottingham University Hospitals NHS Trust

Nottingham, NG7 2UH, United Kingdom

Location

MeSH Terms

Conditions

Hemophilia B; Hemophilia A

Interventions

Protein C

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked

Intervention Hierarchy (Ancestors)

Enzyme Precursors; Enzymes and Coenzymes; Glycoproteins; Glycoconjugates; Carbohydrates; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Protein Precursors; Blood Coagulation Factor Inhibitors; Biological Factors

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2023
• First Posted: March 29, 2023
• Study Start: July 28, 2023
• Primary Completion: November 14, 2024
• Study Completion: February 24, 2025
• Last Updated: March 11, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1); US (3); IT (1); AR (1); DE (1); AU (2); IN (1); ES (1); FR (4); TW (3); TU (2)