The Efficacy and Safety of SerpinPC in Participants With Severe Hemophilia A or Moderately Severe to Severe Hemophilia B

Hemophilia A Clinical Trial

— PRESent-2  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05789524
• Other study ID #: AP-0102
• Secondary ID: 2022-502880-39-0
• Status: Recruiting
• Phase: Phase 2
• Start date: July 6, 2023
• Est. completion date: June 5, 2026

Study information

• Verified date: May 2024
• Source: ApcinteX Ltd
• Contact: Centessa Pharmaceuticals
• Phone: 617-468-5770
• Email: presentprogram[@]centessa.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: June 5, 2026
• Est. primary completion date: March 14, 2026
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 12 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Hemophilia A
• Hemophilia B

Intervention

Drug:
• SerpinPC
Administered as SC injection.

Locations

Country	Name	City	State
Armenia	Centre of Haematology named after prof. R. O. Yeolian	Yerevan
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	The Alfred Hospital	Melbourne	Victoria
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	Queen Fabiola Children	Brussels
Canada	Hamilton Health Sciences Corporation	Hamilton	Ontario
Canada	Hamilton Health Sciences Corporation	Hamilton
France	Hôpital Bicêtre	Le Kremlin-Bicêtre
France	Hospices Civils de Lyon (HCL) - Hopital Femme-Mere-Enfant (HFME)	Lyon	Rhone
France	CHU Hotel Dieu	Nantes
France	Hopital Necker - Enfants Malades	Paris	IDF
Germany	Universitätsklinikum Carl Gustav Carus Dresden	Dresden	Sachsen
Germany	University Hospital Frankfurt	Frankfurt	Hesse
India	Christian Medical College & Hospital	Ludhiana	Punjab
India	K J Somaiya Super Speciality Hospital & Research Centre	Mumbai	Maharashtra
Italy	Azienda Ospedaliero-Universitaria Careggi	Florence
Italy	Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico	Milano	MI
Italy	A.O.U Citt della Salute e della Scienza di Torino	Torino
Italy	Presidio Ospedaliero Universitario S. Maria della Misericordia - ASUFC	Udine	UD
Italy	Azienda Ospedaliera Universitaria Integrata Verona	Verona
Poland	Korczowski Bartosz, Gabinet Lekarski	Rzeszów	Podkarpackie
South Africa	Phoenix Pharma Pty Ltd	Port Elizabeth	Eastern Cape
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Regional Universitario de Malaga Hospital Carlos Haya - Hospital Materno-Infantil	Málaga
Spain	Hospital Clínico Universitario Virgen de la Arrixaca	Murcia
Spain	Hospital Universitario Miguel Servet	Zaragoza
Taiwan	China Medical University Hospital	Taichung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	National Taiwan University Hospital	Taipei City
Turkey	Ege University Medical Faculty Pediatric Hospital	Izmir
United Kingdom	Kent Canterbury Hospital	Canterbury	Kent
United Kingdom	University Hospital of Wales	Cardiff
United Kingdom	Glasgow Royal Infirmary	Glasgow
United Kingdom	Barts and London School of Medicine and Dentistry	London
United Kingdom	Imperial College Healthcare NHS Trust	London
United Kingdom	Royal Free London NHS Foundation Trust	London
United Kingdom	Royal Victoria Infirmary	Newcastle Upon Tyne	Tyne And Wear
United Kingdom	Oxford University Hospital	Oxford	Oxfordshire
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Colorado School of Medicine	Aurora	Colorado
United States	East Carolina Univeristy	Greenville	North Carolina
United States	Penn State Hershey Medical Center	Hershey	Pennsylvania
United States	University of Iowa Healthcare	Iowa City	Iowa
United States	Hemophilia Center of Western Pennsylvania	Pittsburgh	Pennsylvania
United States	University of South Florida	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
ApcinteX Ltd	Centessa Pharmaceuticals plc

Countries where clinical trial is conducted

United States,  Armenia,  Australia,  Belgium,  Canada,  France,  Germany,  India,  Italy,  Poland,  South Africa,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annualized Bleeding Rate (ABR) for Treated Bleeds up to Week 24		Up to Week 24
Secondary	Annualized Bleeding Rate (ABR) for Treated Bleeds Up to Week 48		Up to Week 48
Secondary	Annualized Bleeding Rate (ABR) for Treated Spontaneous Bleeds		Up to Week 48
Secondary	Annualized Bleeding Rate (ABR) for Treated Spontaneous Joint Bleeds		Up to Week 48
Secondary	Total Coagulation Factor and/or Bypass Product Consumption During Parts 2 and 3		Up to Week 48
Secondary	Pharmacokinetic Plasma Concentrations of SerpinPC		From Day 1 up to 24 weeks
Secondary	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
Secondary	Number of Participants With Adverse Events (AEs)		From Baseline up to Week 48