Clinical trial NCT05789524: The Efficacy and Safety of SerpinPC in Participants with Severe Hemophilia a or Moderately Severe to Severe Hemophilia B
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Hemophilia a
Hemophilia B
Keywords: SerpinPC
Hemophilia
Lead sponsor: ApcinteX Ltd
Sponsor class: INDUSTRY
Collaborators: name: Centessa Pharmaceuticals plc
First posted: 2023-03-29
Enrollment: 60
Sex: MALE
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Annualized Bleeding Rate (ABR) for Treated Bleeds up to Week 24
timeFrame: Up to Week 24
Secondary outcomes:
measure: Annualized Bleeding Rate (ABR) for Treated Bleeds Up to Week 48
timeFrame: Up to Week 48
measure: Annualized Bleeding Rate (ABR) for Treated Spontaneous Bleeds
timeFrame: Up to Week 48
measure: Annualized Bleeding Rate (ABR) for Treated Spontaneous Joint Bleeds
timeFrame: Up to Week 48
measure: Total Coagulation Factor and/or Bypass Product Consumption During Parts 2 and 3
timeFrame: Up to Week 48
measure: Pharmacokinetic Plasma Concentrations of SerpinPC
timeFrame: From Day 1 up to 24 weeks
measure: Haemophilia-specific QoL Instrument for Adults (Haem-A-QoL) Physical Health scale in participants aged 17 to ≤65 years with hemophilia
timeFrame: From Baseline up to 24 weeks
measure: Number of Participants With Adverse Events (AEs)
timeFrame: From Baseline up to Week 48
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado School of Medicine
state: Colorado
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Indianapolis
country: United States
facility: Indiana Hemophilia and Thrombosis Center, Inc.
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Healthcare
state: Iowa
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center
state: Minnesota
city: Greenville
country: United States
facility: East Carolina Univeristy
state: North Carolina
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Hemophilia Center of Western Pennsylvania
state: Pennsylvania
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston-Gulf States HTC
state: Texas
city: Yerevan
country: Armenia
facility: Yeolyan Hematology and Oncology Center, MoH of Armenia CJSC
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Brussels
country: Belgium
facility: Queen Fabiola Children
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Hamilton
country: Canada
facility: Hamilton Health Sciences Corporation
state: Ontario
city: Hamilton
country: Canada
facility: Hamilton Health Sciences Corporation
city: Toronto
country: Canada
facility: Unity Health Toronto
city: Paris
country: France
facility: Hopital Necker - Enfants Malades
state: IDF
city: Lyon
country: France
facility: Hospices Civils de Lyon (HCL) - Hopital Femme-Mere-Enfant (HFME)
state: Rhone
city: Le Kremlin-Bicêtre
country: France
facility: Hôpital Bicêtre
city: Frankfurt
country: Germany
facility: University Hospital Frankfurt
state: Hesse
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus Dresden
state: Sachsen
city: Berlin
country: Germany
facility: Klinik fur Angiologie Hamostaseologie Haus 12 A Gerinnungssprechstunde
city: Mumbai
country: India
facility: K J Somaiya Super Speciality Hospital & Research Centre
state: Maharashtra
city: Ludhiāna
country: India
facility: Christian Medical College & Hospital
state: Punjab
city: Milano
country: Italy
facility: Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
state: MI
city: Udine
country: Italy
facility: Presidio Ospedaliero Universitario S. Maria della Misericordia - ASUFC
state: UD
city: Florence
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi
city: Torino
country: Italy
facility: A.O.U Citt della Salute e della Scienza di Torino
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Verona
city: Rzeszów
country: Poland
facility: Korczowski Bartosz, Gabinet Lekarski
state: Podkarpackie
city: Wrocław
country: Poland
facility: Kl Hemat Now Krwi i Trans USK
state: Woj. Dolnośląskie
city: Port Elizabeth
country: South Africa
facility: Phoenix Pharma Pty Ltd
state: Eastern Cape
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Murcia
country: Spain
facility: Hospital Clínico Universitario Virgen de la Arrixaca
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Malaga Hospital Carlos Haya - Hospital Materno-Infantil
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Edirne
country: Turkey
facility: Trakya University Haematology Clinic
city: Istanbul
country: Turkey
facility: Istanbul University Oncology Institute
city: İzmir
country: Turkey
facility: Kocaeli Universitesi Tip Fakultesi
city: İzmir
country: Turkey
facility: Ege University Hospital Internal Disease
city: İzmir
country: Turkey
facility: Ege University Medical Faculty Pediatric Hospital
city: Samsun
country: Turkey
facility: Ondokuz Mayis University Medical Faculty
city: Canterbury
country: United Kingdom
facility: Kent Canterbury Hospital
state: Kent
city: Oxford
country: United Kingdom
facility: Oxford University Hospital
state: Oxfordshire
city: Newcastle Upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary
state: Tyne and Wear
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
city: Glasgow
country: United Kingdom
facility: Glasgow Royal Infirmary
city: London
country: United Kingdom
facility: Barts and London School of Medicine and Dentistry
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
References: