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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)

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ClinicalTrials.gov Identifier: NCT05789524
Recruitment Status : Recruiting
First Posted : March 29, 2023
Last Update Posted : November 8, 2023
Sponsor:
Collaborator:
Centessa Pharmaceuticals plc
Information provided by (Responsible Party):
ApcinteX Ltd

Study Description
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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.


Condition or disease Intervention/treatment Phase
Hemophilia A Hemophilia B Drug: SerpinPC Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 6, 2023
Estimated Primary Completion Date : March 14, 2026
Estimated Study Completion Date : June 5, 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hemophilia
Drug Information available for: Protein C

Arms and Interventions
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Arm Intervention/treatment
Experimental: Part 1 - Cohort 1: SerpinPC
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.
 Drug: SerpinPC
Administered as SC injection.
Other Name: Activated Protein C (APC) inhibitor
Experimental: Part 1 - Cohort 2: SerpinPC
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.
 Drug: SerpinPC
Administered as SC injection.
Other Name: Activated Protein C (APC) inhibitor
Experimental: Part 1 - Cohort 3: SerpinPC
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.
 Drug: SerpinPC
Administered as SC injection.
Other Name: Activated Protein C (APC) inhibitor
Experimental: Part 2 - SerpinPC (Dose-confirmatory phase)
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.
 Drug: SerpinPC
Administered as SC injection.
Other Name: Activated Protein C (APC) inhibitor
Experimental: Part 3 - SerpinPC (Extension phase)
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).
 Drug: SerpinPC
Administered as SC injection.
Other Name: Activated Protein C (APC) inhibitor


Outcome Measures
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Primary Outcome Measures :
  1. Annualized Bleeding Rate (ABR) for Treated Bleeds up to Week 24 [ Time Frame: Up to Week 24 ]

Secondary Outcome Measures :
  1. Annualized Bleeding Rate (ABR) for Treated Bleeds Up to Week 48 [ Time Frame: Up to Week 48 ]
  2. Annualized Bleeding Rate (ABR) for Treated Spontaneous Bleeds [ Time Frame: Up to Week 48 ]
  3. Annualized Bleeding Rate (ABR) for Treated Spontaneous Joint Bleeds [ Time Frame: Up to Week 48 ]
  4. Total Coagulation Factor and/or Bypass Product Consumption During Parts 2 and 3 [ Time Frame: Up to Week 48 ]
  5. Pharmacokinetic Plasma Concentrations of SerpinPC [ Time Frame: From Day 1 up to 24 weeks ]
  6. Haemophilia-specific QoL Instrument for Adults (Haem-A-QoL) Physical Health scale in participants aged 17 to ≤65 years with hemophilia [ Time Frame: From Baseline up to 24 weeks ]
    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.

  7. Number of Participants With Adverse Events (AEs) [ Time Frame: From Baseline up to Week 48 ]

Eligibility Criteria
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Ages Eligible for Study:   12 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05789524


Contacts
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Contact: Centessa Pharmaceuticals 617-468-5770 presentprogram@centessa.com

Locations
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Sponsors and Collaborators
ApcinteX Ltd
Centessa Pharmaceuticals plc
More Information
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Responsible Party: ApcinteX Ltd
ClinicalTrials.gov Identifier: NCT05789524    
Other Study ID Numbers: AP-0102
2022-502880-39-00 ( Other Identifier: EU CT Number )
First Posted: March 29, 2023    Key Record Dates
Last Update Posted: November 8, 2023
Last Verified: November 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by ApcinteX Ltd:
SerpinPC
Hemophilia
Additional relevant MeSH terms:
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Hemophilia A
Hemophilia B
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
 Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Protein C
Anticoagulants
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action