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The Efficacy and Safety of SerpinPC in Participants With Severe Hemophilia A or Moderately Severe to Severe Hemophilia B (PRESent-2)

Primary Purpose

Hemophilia A, 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 A focused on measuring SerpinPC, Hemophilia

Eligibility Criteria

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

Inclusion Criteria: 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 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 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 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 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 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 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 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 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 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 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 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: Known severe thrombophilia (defined as antithrombin deficiency and/or protein S deficiency and or protein C deficiency). Participant with previous factor VIII or 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 kg OR body mass index >40 Kilograms(kg)/meter square (m2) Has active cancer and/or requires therapy for cancer, except for basal cell carcinoma Participation in another clinical trial (except for AP-0105) during the 30 days before Screening Use of emicizumab in the 24 weeks before Baseline (Day 0) Prior, ongoing, or planned treatment with gene therapy for hemophilia 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/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 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. YeolianRecruiting
  • Phoenix Pharma Pty LtdRecruiting
  • China Medical University HospitalRecruiting
  • Taichung Veterans General HospitalRecruiting
  • National Taiwan University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Part 1 - Cohort 1: SerpinPC

Part 1 - Cohort 2: SerpinPC

Part 1 - Cohort 3: SerpinPC

Part 2 - SerpinPC (Dose-confirmatory phase)

Part 3 - SerpinPC (Extension phase)

Arm Description

Participants will receive SerpinPC 1.2 mg/kg SC Injection QW for 24 weeks after a minimum of 12 weeks of a prospective observation period.

Participants will receive SerpinPC 1.2 mg/kg SC Injection Q2W for 24 weeks after a minimum of 12 weeks of a prospective observation period.

Participants will receive SerpinPC 1.2 mg/kg SC Injection Q4W for 24 weeks after a minimum of 12 weeks of a prospective observation period.

After a minimum of 24 weeks of prospective observation, participants will receive SerpinPC at dose of 1.2 mg/kg Q2W for 24 weeks in Part 2, unless the Interim Analysis (IA) shows a greater benefit-risk profile with either the 1.2 mg/kg QW or Q4W treatment regimens.

After completion of dosing in Part 1 or Part 2, participants will continue treatment with SerpinPC at the dose of SerpinPC selected for Part 2 in a 24-week extension phase (Part 3).

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 Parts 2 and 3
Pharmacokinetic Plasma Concentrations of SerpinPC
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.
Number of Participants With Adverse Events (AEs)

Full Information

First Posted
March 16, 2023
Last Updated
October 19, 2023
Sponsor
ApcinteX Ltd
Collaborators
Centessa Pharmaceuticals plc
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1. Study Identification

Unique Protocol Identification Number
NCT05789524
Brief Title
The Efficacy and Safety of SerpinPC in Participants With Severe Hemophilia A or Moderately Severe to Severe Hemophilia B
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 6, 2023 (Actual)
Primary Completion Date
March 14, 2026 (Anticipated)
Study Completion Date
June 5, 2026 (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 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.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Part 1 - Cohort 1: SerpinPC
Arm Type
Experimental
Arm Description
Participants will receive SerpinPC 1.2 mg/kg SC Injection QW for 24 weeks after a minimum of 12 weeks of a prospective observation period.
Arm Title
Part 1 - Cohort 2: SerpinPC
Arm Type
Experimental
Arm Description
Participants will receive SerpinPC 1.2 mg/kg SC Injection Q2W for 24 weeks after a minimum of 12 weeks of a prospective observation period.
Arm Title
Part 1 - Cohort 3: SerpinPC
Arm Type
Experimental
Arm Description
Participants will receive SerpinPC 1.2 mg/kg SC Injection Q4W for 24 weeks after a minimum of 12 weeks of a prospective observation period.
Arm Title
Part 2 - SerpinPC (Dose-confirmatory phase)
Arm Type
Experimental
Arm Description
After a minimum of 24 weeks of prospective observation, participants will receive SerpinPC at dose of 1.2 mg/kg Q2W for 24 weeks in Part 2, unless the Interim Analysis (IA) shows a greater benefit-risk profile with either the 1.2 mg/kg QW or Q4W treatment regimens.
Arm Title
Part 3 - SerpinPC (Extension phase)
Arm Type
Experimental
Arm Description
After completion of dosing in Part 1 or Part 2, participants will continue treatment with SerpinPC at the dose of SerpinPC selected for Part 2 in a 24-week extension phase (Part 3).
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 Parts 2 and 3
Time Frame
Up to Week 48
Title
Pharmacokinetic Plasma Concentrations of SerpinPC
Time Frame
From Day 1 up to 24 weeks
Title
Haemophilia-specific QoL Instrument for Adults (Haem-A-QoL) Physical Health scale in participants aged 17 to ≤65 years with hemophilia
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 24 weeks
Title
Number of Participants With Adverse Events (AEs)
Time Frame
From Baseline up to Week 48

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 ≥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 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 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 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 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 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 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 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 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 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 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 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: Known severe thrombophilia (defined as antithrombin deficiency and/or protein S deficiency and or protein C deficiency). Participant with previous factor VIII or 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 kg OR body mass index >40 Kilograms(kg)/meter square (m2) Has active cancer and/or requires therapy for cancer, except for basal cell carcinoma Participation in another clinical trial (except for AP-0105) during the 30 days before Screening Use of emicizumab in the 24 weeks before Baseline (Day 0) Prior, ongoing, or planned treatment with gene therapy for hemophilia 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/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 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
City
Yerevan
ZIP/Postal Code
14
Country
Armenia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Heghine Khachatryan
Facility Name
Phoenix Pharma Pty Ltd
City
Port Elizabeth
State/Province
Eastern Cape
ZIP/Postal Code
6001
Country
South Africa
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Daniel Malan
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
Facility Name
Taichung Veterans General Hospital
City
Taichung
ZIP/Postal Code
40705
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jiaan-Der Wang
Facility Name
National Taiwan University Hospital
City
Taipei City
ZIP/Postal Code
10004
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sheng-Chieh Chou

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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