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A Study of SerpinPC in Participants With Hemophilia B (HemB) With Inhibitors (PRESent-3)

Primary Purpose

Hemophilia B With Inhibitor, Hemophilia B

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
SerpinPC
Sponsored by
ApcinteX Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hemophilia B With Inhibitor focused on measuring SerpinPC, Hemophilia

Eligibility Criteria

12 Years - 65 Years (Child, Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria: Male participants greater than or equal to (>=) 12 and less than or equal to (<=) 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 international unit/Milliliter (IU/mL) [<=5 percent (%)]). 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. Historical or ongoing Factor IX inhibitor with bypass agents based on medical records or laboratory reports. 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 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. 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). 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. 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. 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. 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. 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: Known severe thrombophilia (defined as antithrombin deficiency and/or protein S deficiency and/or protein C deficiency). Participant with previous factor IX inhibitor who responded to immune tolerance induction and remains on prophylactic factor concentrate. Previous deep vein thrombosis, pulmonary embolism, myocardial infarction, or stroke. History of intolerance to SC injections. Uncontrolled hypertension (systolic blood pressure >160 millimeter of mercury (mm Hg); diastolic blood pressure >100 mm Hg). Weight >150 kilograms (kg) OR body mass index >40 kg/meter square (m^2). Has active cancer and/or requires therapy for cancer, except for basal cell carcinoma. Participation in another clinical trial (except for AP-0105 [NCT05605678]) during the 30 days before screening. Prior, ongoing, or planned treatment with gene therapy for HemB 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. History of or other evidence of recent alcohol or drug abuse as determined by the Investigator (in the 12 months before screening). 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. 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 participant unsuitable for enrollment, or could interfere with participation in, or completion of the study.

Sites / Locations

  • Centre of Haematology named after prof. R. O. Yeolian/ Hemophilia centerRecruiting
  • Chung Shan Medical UniversityRecruiting
  • China Medical University HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

SerpinPC

Arm Description

Participants will receive SerpinPC 1.2 milligrams/kilogram (mg/kg) subcutaneous (SC) injection every 2 weeks (Q2W) for 48 weeks after a prospective observation of 12 weeks for all participants, either in a prior non-interventional study (AP-0105[NCT05605678]) or as part of the ongoing study observational period.

Outcomes

Primary Outcome Measures

Annualized Bleeding Rate (ABR) for Treated Bleeds up to Week 24

Secondary Outcome Measures

Annualized Bleeding Rate (ABR) for Treated Bleeds Up to Week 48
Annualized Bleeding Rate (ABR) for Treated Spontaneous Bleeds
Annualized Bleeding Rate (ABR) for Treated Spontaneous Joint Bleeds
Total Coagulation Factor and/or Bypass Product Consumption During SerpinPC Treatment
Pharmacokinetic Concentrations of SerpinPC
Haemophilia Quality-of-Life Questionnaire for Adults (Haem-A-QoL) Physical Health Scale
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.
Number of participants with Adverse events (AEs)
Number of Participants with Persistent High-titer Antidrug Antibodies (ADAs)
Number of Participants with Severity of Injection-site Reactions

Full Information

First Posted
March 16, 2023
Last Updated
October 5, 2023
Sponsor
ApcinteX Ltd
Collaborators
Centessa Pharmaceuticals plc
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1. Study Identification

Unique Protocol Identification Number
NCT05789537
Brief Title
A Study of SerpinPC in Participants With Hemophilia B (HemB) With Inhibitors
Acronym
PRESent-3
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

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 28, 2023 (Actual)
Primary Completion Date
September 8, 2025 (Anticipated)
Study Completion Date
October 28, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ApcinteX Ltd
Collaborators
Centessa Pharmaceuticals plc

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia B With Inhibitor, Hemophilia B
Keywords
SerpinPC, Hemophilia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
SerpinPC
Arm Type
Experimental
Arm Description
Participants will receive SerpinPC 1.2 milligrams/kilogram (mg/kg) subcutaneous (SC) injection every 2 weeks (Q2W) for 48 weeks after a prospective observation of 12 weeks for all participants, either in a prior non-interventional study (AP-0105[NCT05605678]) or as part of the ongoing study observational period.
Intervention Type
Drug
Intervention Name(s)
SerpinPC
Other Intervention Name(s)
Activated Protein C (APC) inhibitor
Intervention Description
Administered as SC injection.
Primary Outcome Measure Information:
Title
Annualized Bleeding Rate (ABR) for Treated Bleeds up to Week 24
Time Frame
Up to Week 24
Secondary Outcome Measure Information:
Title
Annualized Bleeding Rate (ABR) for Treated Bleeds Up to Week 48
Time Frame
Up to Week 48
Title
Annualized Bleeding Rate (ABR) for Treated Spontaneous Bleeds
Time Frame
Up to Week 48
Title
Annualized Bleeding Rate (ABR) for Treated Spontaneous Joint Bleeds
Time Frame
Up to Week 48
Title
Total Coagulation Factor and/or Bypass Product Consumption During SerpinPC Treatment
Time Frame
Up to Week 48
Title
Pharmacokinetic Concentrations of SerpinPC
Time Frame
From Day 1(Pre-dose) up to Week 48(Post-dose)
Title
Haemophilia Quality-of-Life Questionnaire for Adults (Haem-A-QoL) Physical Health Scale
Description
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.
Time Frame
From Baseline up to Week 48
Title
Number of participants with Adverse events (AEs)
Time Frame
From Baseline up to Week 52
Title
Number of Participants with Persistent High-titer Antidrug Antibodies (ADAs)
Time Frame
From Baseline up to Week 48
Title
Number of Participants with Severity of Injection-site Reactions
Time Frame
Baseline up to Week 44

10. Eligibility

Sex
Male
Gender Based
Yes
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male participants greater than or equal to (>=) 12 and less than or equal to (<=) 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 international unit/Milliliter (IU/mL) [<=5 percent (%)]). 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. Historical or ongoing Factor IX inhibitor with bypass agents based on medical records or laboratory reports. 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 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. 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). 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. 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. 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. 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. 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: Known severe thrombophilia (defined as antithrombin deficiency and/or protein S deficiency and/or protein C deficiency). Participant with previous factor IX inhibitor who responded to immune tolerance induction and remains on prophylactic factor concentrate. Previous deep vein thrombosis, pulmonary embolism, myocardial infarction, or stroke. History of intolerance to SC injections. Uncontrolled hypertension (systolic blood pressure >160 millimeter of mercury (mm Hg); diastolic blood pressure >100 mm Hg). Weight >150 kilograms (kg) OR body mass index >40 kg/meter square (m^2). Has active cancer and/or requires therapy for cancer, except for basal cell carcinoma. Participation in another clinical trial (except for AP-0105 [NCT05605678]) during the 30 days before screening. Prior, ongoing, or planned treatment with gene therapy for HemB 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. History of or other evidence of recent alcohol or drug abuse as determined by the Investigator (in the 12 months before screening). 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. 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 participant unsuitable for enrollment, or could interfere with participation in, or completion of the study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Centessa Pharmaceuticals
Phone
617-468-5770
Email
presentprogram@centessa.com
Facility Information:
Facility Name
Centre of Haematology named after prof. R. O. Yeolian/ Hemophilia center
City
Yerevan
ZIP/Postal Code
0014
Country
Armenia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Heghine Khachatryan
Facility Name
Chung Shan Medical University
City
Taichung
ZIP/Postal Code
40201
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Te-Fu Weng
Facility Name
China Medical University Hospital
City
Taichung
ZIP/Postal Code
40447
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ching-Tien Peng

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

A Study of SerpinPC in Participants With Hemophilia B (HemB) With Inhibitors

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