The Efficacy and Safety of SerpinPC in Participants with Severe Hemophilia a or Moderately Severe to Severe Hemophilia B

NCT05789524 | Terminated Phase 2 DMC FDA Drug

• 2 other identifiers: AP-01022022-502880-39-00
• Study Type: interventional
• Target: 60
• Locations: 15 countries
• Sites: 59

Brief Summary

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.

Conditions

Hemophilia a; 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 (7)

• 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

Study Arms (5)

Part 1 - Cohort 1: SerpinPC

EXPERIMENTAL

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

Part 1 - Cohort 2: SerpinPC

EXPERIMENTAL

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

Part 1 - Cohort 3: SerpinPC

EXPERIMENTAL

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

Part 2 - SerpinPC (Dose-confirmatory phase)

EXPERIMENTAL

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

Part 3 - SerpinPC (Extension phase)

EXPERIMENTAL

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

Interventions

SerpinPC DRUG

Administered as SC injection.

Also known as: Activated Protein C (APC) inhibitor

Part 1 - Cohort 1: SerpinPC; Part 1 - Cohort 2: SerpinPC; Part 1 - Cohort 3: SerpinPC; Part 2 - SerpinPC (Dose-confirmatory phase); Part 3 - SerpinPC (Extension phase)

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 ≥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
• 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 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
• 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
• 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
• 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
• 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
• 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(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
• 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 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.

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 VIII or 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 kg OR body mass index \>40 Kilograms(kg)/meter square (m2)
• Has active cancer and/or requires therapy for cancer, except for basal cell carcinoma
• Participation in another clinical trial (except for AP-0105) during the 30 days before Screening
• Use of emicizumab in the 24 weeks before Baseline (Day 0)
• Prior, ongoing, or planned treatment with gene therapy for hemophilia
• 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/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
• 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

Sponsors & Collaborators

• ApcinteX Ltd: lead
• Centessa Pharmaceuticals plc: collaborator

Study Sites (59)

University of Colorado School of Medicine

Aurora, Colorado, 80045-7202, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

Indiana Hemophilia and Thrombosis Center, Inc.

Indianapolis, Indiana, 46260, United States

Location

University of Iowa Healthcare

Iowa City, Iowa, 52246, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota Medical Center

Minneapolis, Minnesota, 55455, United States

Location

East Carolina Univeristy

Greenville, North Carolina, 27834, United States

Location

Penn State Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Hemophilia Center of Western Pennsylvania

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Texas Health Science Center at Houston-Gulf States HTC

Houston, Texas, 77030, United States

Location

Yeolyan Hematology and Oncology Center, MoH of Armenia CJSC

Yerevan, Yerevan, 14, Armenia

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Queen Fabiola Children

Brussels, Brussels Capital, 1020, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, Brussels Capital, 1200, Belgium

Location

Hamilton Health Sciences Corporation

Hamilton, Hamilton, L8S 4K1, Canada

Location

Hamilton Health Sciences Corporation

Hamilton, Ontario, L8S4K1, Canada

Location

Unity Health Toronto

Toronto, M5B 1W8, Canada

Location

Hôpital Bicêtre

Le Kremlin-Bicêtre, France, 94270, France

Location

Hopital Necker - Enfants Malades

Paris, IDF, 75015, France

Location

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

Lyon, Rhone, 69500, France

Location

University Hospital Frankfurt

Frankfurt am Main, Hesse, 60590, Germany

Location

Universitätsklinikum Carl Gustav Carus Dresden

Dresden, Saxony, 1307, Germany

Location

Klinik fur Angiologie Hamostaseologie Haus 12 A Gerinnungssprechstunde

Berlin, State of Berlin, 10249, Germany

Location

K J Somaiya Super Speciality Hospital & Research Centre

Mumbai, Maharashtra, 400022, India

Location

Christian Medical College & Hospital

Ludhiana, Punjab, 141008, India

Location

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico

Milan, MI, 20122, Italy

Location

A.O.U Citt della Salute e della Scienza di Torino

Torino, Torino, 10126, Italy

Location

Presidio Ospedaliero Universitario S. Maria della Misericordia - ASUFC

Udine, UD, 33100, Italy

Location

Azienda Ospedaliera Universitaria Integrata Verona

Verona, Verona, 37126, Italy

Location

Azienda Ospedaliero-Universitaria Careggi

Florence, 50134, Italy

Location

Korczowski Bartosz, Gabinet Lekarski

Rzeszów, Podkarpackie Voivodeship, 35-302, Poland

Location

Kl Hemat Now Krwi i Trans USK

Wroclaw, Woj. Dolnośląskie, 50-367, Poland

Location

Phoenix Pharma Pty Ltd

Port Elizabeth, Eastern Cape, 6001, South Africa

Location

Hospital Clínico Universitario Virgen de la Arrixaca

Murcia, Murcia, 30120, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, Spain, 8035, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, Zaragoza, 50009, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

Hospital Regional Universitario de Malaga Hospital Carlos Haya - Hospital Materno-Infantil

Málaga, 29010, Spain

Location

Taipei Veterans General Hospital

Taipei, Taipei, 11217, Taiwan

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

National Taiwan University Hospital

Taipei, 10004, Taiwan

Location

Ege University Medical Faculty Pediatric Hospital

Izmir, İzmir, 35100, Turkey (Türkiye)

Location

Trakya University Haematology Clinic

Edirne, 22030, Turkey (Türkiye)

Location

Istanbul University Oncology Institute

Istanbul, 34093, Turkey (Türkiye)

Location

Kocaeli Universitesi Tip Fakultesi

Izmir, 1000, Turkey (Türkiye)

Location

Ege University Hospital Internal Disease

Izmir, 35100, Turkey (Türkiye)

Location

Ondokuz Mayis University Medical Faculty

Samsun, 55200, Turkey (Türkiye)

Location

University Hospitals Birmingham NHS Foundation Trust

Birmingham, Birmingham, B15 2GW, United Kingdom

Location

University Hospital of Wales

Cardiff, Cardiff, CF14 4XW, United Kingdom

Location

Glasgow Royal Infirmary

Glasgow, Glasgow, G4 0SF, United Kingdom

Location

Kent Canterbury Hospital

Canterbury, Kent, CT1 3NG, United Kingdom

Location

Barts and London School of Medicine and Dentistry

London, London, E1 2AT, United Kingdom

Location

Royal Free London NHS Foundation Trust

London, London, NW3 2QG, United Kingdom

Location

Imperial College Healthcare NHS Trust

London, London, W2 1NY, United Kingdom

Location

Oxford University Hospital

Oxford, Oxfordshire, OX3 9DU, United Kingdom

Location

Southampton General Hospital

Southampton, Southampton, S016 6YD, United Kingdom

Location

Royal Victoria Infirmary

Newcastle upon Tyne, Tyne and Wear, NE1 4LP, United Kingdom

Location

MeSH Terms

Conditions

Hemophilia A; Hemophilia B

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: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2023
• First Posted: March 29, 2023
• Study Start: July 6, 2023
• Primary Completion: November 14, 2024
• Study Completion: February 28, 2025
• Last Updated: March 11, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3); PL (2); CA (3); TW (4); AU (2); ES (5); US (10); IN (2); IT (5); GB (10); BE (2); AR (1); DE (3); TU (6); ZA (1)