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

NCT ID: NCT05789524

Last Updated: 2025-03-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-07-06
• Study Completion Date: 2025-02-28

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

SerpinPC

Intervention Type: DRUG

Administered as SC injection.

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.

Group Type: EXPERIMENTAL

SerpinPC

Intervention Type: DRUG

Administered as SC injection.

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.

Group Type: EXPERIMENTAL

SerpinPC

Intervention Type: DRUG

Administered as SC injection.

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.

Group Type: EXPERIMENTAL

SerpinPC

Intervention Type: DRUG

Administered as SC injection.

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).

Group Type: EXPERIMENTAL

SerpinPC

Intervention Type: DRUG

Administered as SC injection.

Interventions

SerpinPC

Administered as SC injection.

Intervention Type: DRUG

Other Intervention Names

Activated Protein C (APC) inhibitor

Eligibility Criteria

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

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Centessa Pharmaceuticals plc

INDUSTRY

Sponsor Role: collaborator

ApcinteX Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Colorado School of Medicine

Aurora, Colorado, United States

University of South Florida

Tampa, Florida, United States

Indiana Hemophilia and Thrombosis Center, Inc.

Indianapolis, Indiana, United States

University of Iowa Healthcare

Iowa City, Iowa, United States

University of Michigan

Ann Arbor, Michigan, United States

University of Minnesota Medical Center

Minneapolis, Minnesota, United States

East Carolina Univeristy

Greenville, North Carolina, United States

Penn State Hershey Medical Center

Hershey, Pennsylvania, United States

Hemophilia Center of Western Pennsylvania

Pittsburgh, Pennsylvania, United States

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

Houston, Texas, United States

Yeolyan Hematology and Oncology Center, MoH of Armenia CJSC

Yerevan, Yerevan, Armenia

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

The Alfred Hospital

Melbourne, Victoria, Australia

Queen Fabiola Children

Brussels, Brussels Capital, Belgium

Cliniques Universitaires Saint-Luc

Brussels, Brussels Capital, Belgium

Hamilton Health Sciences Corporation

Hamilton, Hamilton, Canada

Hamilton Health Sciences Corporation

Hamilton, Ontario, Canada

Unity Health Toronto

Toronto, , Canada

Hôpital Bicêtre

Le Kremlin-Bicêtre, France, France

Hopital Necker - Enfants Malades

Paris, IDF, France

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

Lyon, Rhone, France

University Hospital Frankfurt

Frankfurt am Main, Hesse, Germany

Universitätsklinikum Carl Gustav Carus Dresden

Dresden, Saxony, Germany

Klinik fur Angiologie Hamostaseologie Haus 12 A Gerinnungssprechstunde

Berlin, State of Berlin, Germany

K J Somaiya Super Speciality Hospital & Research Centre

Mumbai, Maharashtra, India

Christian Medical College & Hospital

Ludhiana, Punjab, India

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico

Milan, MI, Italy

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

Torino, Torino, Italy

Presidio Ospedaliero Universitario S. Maria della Misericordia - ASUFC

Udine, UD, Italy

Azienda Ospedaliera Universitaria Integrata Verona

Verona, Verona, Italy

Azienda Ospedaliero-Universitaria Careggi

Florence, , Italy

Korczowski Bartosz, Gabinet Lekarski

Rzeszów, Podkarpackie Voivodeship, Poland

Kl Hemat Now Krwi i Trans USK

Wroclaw, Woj. Dolnośląskie, Poland

Phoenix Pharma Pty Ltd

Port Elizabeth, Eastern Cape, South Africa

Hospital Clínico Universitario Virgen de la Arrixaca

Murcia, Murcia, Spain

Hospital Universitari Vall d'Hebron

Barcelona, Spain, Spain

Hospital Universitario Miguel Servet

Zaragoza, Zaragoza, Spain

Hospital Universitario La Paz

Madrid, , Spain

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

Málaga, , Spain

Taipei Veterans General Hospital

Taipei, Taipei, Taiwan

China Medical University Hospital

Taichung, , Taiwan

Taichung Veterans General Hospital

Taichung, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Ege University Medical Faculty Pediatric Hospital

Izmir, İzmir, Turkey (Türkiye)

Trakya University Haematology Clinic

Edirne, , Turkey (Türkiye)

Istanbul University Oncology Institute

Istanbul, , Turkey (Türkiye)

Kocaeli Universitesi Tip Fakultesi

Izmir, , Turkey (Türkiye)

Ege University Hospital Internal Disease

Izmir, , Turkey (Türkiye)

Ondokuz Mayis University Medical Faculty

Samsun, , Turkey (Türkiye)

University Hospitals Birmingham NHS Foundation Trust

Birmingham, Birmingham, United Kingdom

University Hospital of Wales

Cardiff, Cardiff, United Kingdom

Glasgow Royal Infirmary

Glasgow, Glasgow, United Kingdom

Kent Canterbury Hospital

Canterbury, Kent, United Kingdom

Barts and London School of Medicine and Dentistry

London, London, United Kingdom

Royal Free London NHS Foundation Trust

London, London, United Kingdom

Imperial College Healthcare NHS Trust

London, London, United Kingdom

Oxford University Hospital

Oxford, Oxfordshire, United Kingdom

Southampton General Hospital

Southampton, Southampton, United Kingdom

Royal Victoria Infirmary

Newcastle upon Tyne, Tyne and Wear, United Kingdom

Countries

United States; Armenia; Australia; Belgium; Canada; France; Germany; India; Italy; Poland; South Africa; Spain; Taiwan; Turkey (Türkiye); United Kingdom

Other Identifiers

2022-502880-39-00

Identifier Type: OTHER

Identifier Source: secondary_id

AP-0102

Identifier Type: -

Identifier Source: org_study_id