Clinical trial NCT05789537: A Study of SerpinPC in Participants with Hemophilia B (HemB) with Inhibitors
Official title: A Global, Open-label Study to Investigate the Efficacy and Safety of SerpinPC in Subjects with Hemophilia B with Inhibitors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Hemophilia B with Inhibitor
Hemophilia B
Keywords: SerpinPC
Hemophilia
Lead sponsor: ApcinteX Ltd
Sponsor class: INDUSTRY
Collaborators: name: Centessa Pharmaceuticals plc
First posted: 2023-03-29
Enrollment: 3
Sex: MALE
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Male participants greater than or equal to (\>=) 12 and less than or equal to (\<=) 65 years of age at the time of informed consent.
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 HemB (defined as factor IX \<=0.05 international unit/Milliliter (IU/mL) \[\<=5 percent (%)\]).
4. 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.
5. Historical or ongoing Factor IX inhibitor with bypass agents based on medical records or laboratory reports.
6. 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
7. 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.
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 \<=750 micrograms/Liter (mc/L); in cases where there is a resolving bleed, the exclusion threshold is \<=1750 mg/L at Screening and Pre-dosing visits.
10. 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.
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 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.

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 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 kilograms (kg) OR body mass index \>40 kg/meter square (m\^2).
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 \[NCT05605678\]) during the 30 days before screening.
9. Prior, ongoing, or planned treatment with gene therapy for HemB
10. 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.
11. History of or other evidence of recent alcohol or drug abuse as determined by the Investigator (in the 12 months before screening).
12. 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.
13. Current or planned treatment with anticoagulant or antiplatelet drugs
14. Is planning to donate/bank sperm during SerpinPC treatment AND within 30 days of last dose of SerpinPC.
15. 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 SerpinPC Treatment
timeFrame: Up to Week 48
measure: Pharmacokinetic Concentrations of SerpinPC
timeFrame: From Day 1(Pre-dose) up to Week 48(Post-dose)
measure: Haemophilia Quality-of-Life Questionnaire for Adults (Haem-A-QoL) Physical Health Scale
timeFrame: From Baseline up to Week 48
measure: Number of participants with Adverse events (AEs)
timeFrame: From Baseline up to Week 52
measure: Number of Participants with Persistent High-titer Antidrug Antibodies (ADAs)
timeFrame: From Baseline up to Week 48
measure: Number of Participants with Severity of Injection-site Reactions
timeFrame: Baseline up to Week 44
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: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Yerevan
country: Armenia
facility: Centre of Haematology named after prof. R. O. Yeolian/ Hemophilia center
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Le Kremlin-Bicêtre
country: France
facility: Hopital Bicetre
city: Lille
country: France
facility: CHRU de Lille Centre de biologie et pathologie
city: Lyon
country: France
facility: Hospices Civils de Lyon (HCL) - Hopital Femme-Mere-Enfant (HFME)
city: Paris
country: France
facility: Hopital Necker - Enfants Malades
city: Frankfurt
country: Germany
facility: University Hospital Frankfurt M
city: Mumbai
country: India
facility: K J Somaiya Super Speciality Hospital & Research Centre
state: Maharashtra
city: Milan
country: Italy
facility: Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Taichung city
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taichung
country: Taiwan
facility: Chung Shan Medical University
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Istanbul
country: Turkey
facility: Istanbul University Oncology Institute
city: İzmir
country: Turkey
facility: Ege University Medical Faculty Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
Study officials:
References: