A Global, Open-label Study to Investigate the Efficacy and Safety of SerpinPC in Subjects With Hemophilia B With Inhibitors (PRESent-3)

Trial ID: 2022-502881-25-00
Protocol: AP-0103
Sponsor: Apcintex Limited

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Diseases & Conditions

Haemophilia B with anti factor IX Acquired haemophilia

Objectives

The primary objective of this study is to evaluate the **efficacy** and **safety** of prophylactic SerpinPC, administered subcutaneously, in subjects with **Hemophilia B** with inhibitors. This is clinically relevant as it aims to address the therapeutic needs of patients with Hemophilia B who develop inhibitors, which complicates standard treatment approaches and increases the risk of bleeding episodes.

Secondary objectives include:

To evaluate the **tolerability** of SerpinPC, which is crucial for determining the feasibility of long-term use in patients.
To further characterize the **pharmacokinetic (PK) profile** of SerpinPC, providing insights into the drug's absorption, distribution, metabolism, and excretion, which are essential for optimizing dosing regimens.

Participants

The clinical trial involves a total of **14 male participants** diagnosed with **Hemophilia B**, specifically those with inhibitors. The study population consists of males aged between **12 and 65 years**. Participants were selected based on their adequate hematologic, hepatic, and renal function, as well as their ability to document bleeding events and medication usage. The trial excludes female subjects and includes a vulnerable population. Participants are required to have a historically documented factor IX level of ≤0.05 IU/mL and must be willing to discontinue any current prophylaxis programs before the administration of SerpinPC. Lifestyle considerations such as the use of effective contraception for sexually active participants are also part of the study requirements. The trial aims to evaluate the efficacy and safety of prophylactic SerpinPC administered subcutaneously in this specific population.

Plans and Procedures

The clinical trial is designed to evaluate the efficacy and safety of **SerpinPC**, a **human alpha-1 proteinase inhibitor, modified**, administered subcutaneously in subjects with **Hemophilia B** with inhibitors. This is a global, open-label study, categorized as a Phase 4 trial, and is not considered low intervention. The trial aims to assess the prophylactic use of SerpinPC over a maximum treatment period of 48 weeks, with a maximum daily dose of 1.2 mg/kg. The primary endpoint is the annualized bleeding rate (ABR) of treated bleeds during the observation period and the first 24 weeks of SerpinPC administration. Secondary endpoints include ABR of treated bleeds during the first 48 weeks, spontaneous bleeds, joint bleeds, total coagulation factor consumption, pharmacokinetic concentrations of SerpinPC, and quality-of-life assessments.

Participants will be involved in the study for an estimated duration from the recruitment start date on August 21, 2023, until the estimated end date on October 1, 2025. The study includes several key visits: an initial screening visit to confirm eligibility based on criteria such as age, hematologic, hepatic, and renal function, and historical documentation of Hemophilia B. Following the screening, participants will undergo a pre-dosing visit to ensure no active bleeding and to confirm baseline parameters. Regular follow-up visits will be scheduled to monitor safety, efficacy, and pharmacokinetics, with the final visit marking the end of the study. Participants are expected to document bleeding events and medication usage throughout the trial.

Inclusion criteria require male subjects aged 12 to 65 years with adequate organ function and a documented history of Hemophilia B with inhibitors. Participants must be willing to discontinue any current prophylaxis programs before receiving the first dose of SerpinPC. Conditions for early termination from the study include non-compliance with study procedures, withdrawal of consent, or any adverse events that compromise participant safety. The trial is conducted under the sponsorship of APCINTEX LIMITED, with SerpinPC being administered as a solution for injection via subcutaneous route.

Treatment

The clinical trial involves the administration of **SerpinPC**, an experimental medication formulated as a **solution for injection**. The active substance in SerpinPC is the **human alpha-1 proteinase inhibitor, modified**, which is a protein of non-human origin. The medication is administered via **subcutaneous injection**. The dosing regimen for SerpinPC is set at a maximum daily dose of 1.2 mg/kg, with the total dose not exceeding 1.2 mg/kg per day. The treatment period is capped at 48 weeks. The study aims to evaluate the efficacy and safety of SerpinPC in subjects with **hemophilia B** with inhibitors, focusing on its prophylactic use.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified for this study. The trial is designed as an open-label study, meaning that both the researchers and participants are aware of the treatment being administered. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the protocol. The study does not include a pediatric formulation of the medication, and the trial is designated as an orphan drug study, indicating its focus on a rare condition.

Efficacy

The efficacy of SerpinPC in the clinical trial for subjects with **Hemophilia B** with inhibitors will be assessed using several endpoints. The primary endpoint is the annualized bleeding rate (ABR) of treated bleeds during the observation period and the first 24 weeks of treatment with SerpinPC. Secondary endpoints include the ABR of treated bleeds beyond the primary endpoint period, treated spontaneous bleeds, treated spontaneous joint bleeds, and all bleeds requiring treatment. Additionally, the total consumption of coagulation factor and/or bypass products during SerpinPC treatment will be evaluated. Pharmacokinetic (PK) concentrations of SerpinPC will be measured throughout the study, and the Haemophilia Quality-of-Life Questionnaire for Adults (Haem-A-QoL) Physical Health scale will be used for subjects aged 17 to 65 years.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Male subjects ≥12 and ≤65 years of age at the time of informed consent
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 HemB (defined as factor IX ≤0.05 IU/mL [≤5%])
Subjects 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
Historical or ongoing factor IX inhibitor requiring current treatment with bypass agents based on medical records or laboratory reports
Documented ABR of ≥6 in the 12 months before screening (subjects not on prophylaxis regimen) or documented ABR of ≥2 for subjects on prophylaxis regimen
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-0103
No bleeding in the 7 days before Baseline (the prospective observation period can be extended if there is an ongoing active bleed)
D-dimer of ≤750 μg/L; in cases where there is a resolving bleed, the exclusion threshold is ≤1750 mg/L at Screening and Pre-dosing visits
Adequate hematologic function, defined as a platelet count of ≥100,000/μL (≥100 × 109/L) and hemoglobin level of ≥10 g/dL (≥100 g/L or ≥ 6.206 mmol/L) at Screening and Pre-dosing visits
Adequate hepatic function, defined as a total bilirubin level of ≤1.5 × upper level 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 (caregiver assistance allowed for adolescents)
Sexually active subjects 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

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Exclusion Criteria

Known severe thrombophilia (defined as antithrombin deficiency and/or protein S deficiency and/or protein C deficiency)
Patient with previous factor IX inhibitor who responded to immune tolerance induction and remains on prophylactic factor concentrate
Previous deep vein thrombosis (excluding line-associated thrombosis), pulmonary embolism, myocardial infarction, or stroke
History of intolerance to SC injections
Uncontrolled hypertension (systolic blood pressure >160 mm Hg; diastolic blood pressure >100 mm Hg)
Weight >150 kg OR body mass index >40 kg/m2
Has active cancer and/or requires therapy for cancer, except for basal cell carcinoma
Participation in another interventional clinical trial (except for AP-0105) during the 30 days before screening
Ongoing, or planned treatment with gene therapy for HemB
Any major medical, psychological, or psychiatric condition that could cause the subject 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 HIV infection with CD4 count (or T-cell count) of <200 cells/μL within 24 weeks before Screening and Pre-dosing visits. Patients 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
Any other significant conditions or comorbidities that, in the opinion of the Investigator, would make the subject unsuitable for enrollment, or could interfere with participation in, or completion of the study