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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05789524




Registration number
NCT05789524
Ethics application status
Date submitted
16/03/2023
Date registered
29/03/2023

Titles & IDs
Public title
The Efficacy and Safety of SerpinPC in Participants With Severe Hemophilia A or Moderately Severe to Severe Hemophilia B
Scientific 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
Secondary ID [1] 0 0
2022-502880-39-00
Secondary ID [2] 0 0
AP-0102
Universal Trial Number (UTN)
Trial acronym
PRESent-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hemophilia A 0 0
Hemophilia B 0 0
Condition category
Condition code
Blood 0 0 0 0
Clotting disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - SerpinPC

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.

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.

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.

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.

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).


Treatment: Drugs: SerpinPC
Administered as SC injection.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Annualized Bleeding Rate (ABR) for Treated Bleeds up to Week 24
Timepoint [1] 0 0
Up to Week 24
Secondary outcome [1] 0 0
Annualized Bleeding Rate (ABR) for Treated Bleeds Up to Week 48
Timepoint [1] 0 0
Up to Week 48
Secondary outcome [2] 0 0
Annualized Bleeding Rate (ABR) for Treated Spontaneous Bleeds
Timepoint [2] 0 0
Up to Week 48
Secondary outcome [3] 0 0
Annualized Bleeding Rate (ABR) for Treated Spontaneous Joint Bleeds
Timepoint [3] 0 0
Up to Week 48
Secondary outcome [4] 0 0
Total Coagulation Factor and/or Bypass Product Consumption During Parts 2 and 3
Timepoint [4] 0 0
Up to Week 48
Secondary outcome [5] 0 0
Pharmacokinetic Plasma Concentrations of SerpinPC
Timepoint [5] 0 0
From Day 1 up to 24 weeks
Secondary outcome [6] 0 0
Haemophilia-specific QoL Instrument for Adults (Haem-A-QoL) Physical Health scale in participants aged 17 to =65 years with hemophilia
Timepoint [6] 0 0
From Baseline up to 24 weeks
Secondary outcome [7] 0 0
Number of Participants With Adverse Events (AEs)
Timepoint [7] 0 0
From Baseline up to Week 48

Eligibility
Key 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.
Minimum age
12 Years
Maximum age
65 Years
Sex
Males
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
6/07/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
5/06/2026
Actual
Sample size
Target
120
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Iowa
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
North Carolina
Country [6] 0 0
United States of America
State/province [6] 0 0
Pennsylvania
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
Armenia
State/province [8] 0 0
Yerevan
Country [9] 0 0
Belgium
State/province [9] 0 0
Brussels
Country [10] 0 0
Canada
State/province [10] 0 0
Ontario
Country [11] 0 0
Canada
State/province [11] 0 0
Hamilton
Country [12] 0 0
Canada
State/province [12] 0 0
Toronto
Country [13] 0 0
France
State/province [13] 0 0
IDF
Country [14] 0 0
France
State/province [14] 0 0
Rhone
Country [15] 0 0
France
State/province [15] 0 0
Le Kremlin-Bicêtre
Country [16] 0 0
France
State/province [16] 0 0
Nantes
Country [17] 0 0
Germany
State/province [17] 0 0
Hesse
Country [18] 0 0
Germany
State/province [18] 0 0
Sachsen
Country [19] 0 0
Germany
State/province [19] 0 0
Berlin
Country [20] 0 0
India
State/province [20] 0 0
Maharashtra
Country [21] 0 0
India
State/province [21] 0 0
Punjab
Country [22] 0 0
Italy
State/province [22] 0 0
MI
Country [23] 0 0
Italy
State/province [23] 0 0
UD
Country [24] 0 0
Italy
State/province [24] 0 0
Florence
Country [25] 0 0
Italy
State/province [25] 0 0
Torino
Country [26] 0 0
Italy
State/province [26] 0 0
Verona
Country [27] 0 0
Poland
State/province [27] 0 0
Podkarpackie
Country [28] 0 0
Poland
State/province [28] 0 0
Woj. Dolnoslaskie
Country [29] 0 0
South Africa
State/province [29] 0 0
Eastern Cape
Country [30] 0 0
Spain
State/province [30] 0 0
Barcelona
Country [31] 0 0
Spain
State/province [31] 0 0
Madrid
Country [32] 0 0
Spain
State/province [32] 0 0
Murcia
Country [33] 0 0
Spain
State/province [33] 0 0
Málaga
Country [34] 0 0
Spain
State/province [34] 0 0
Zaragoza
Country [35] 0 0
Taiwan
State/province [35] 0 0
Taichung
Country [36] 0 0
Taiwan
State/province [36] 0 0
Taipei City
Country [37] 0 0
Taiwan
State/province [37] 0 0
Taipei
Country [38] 0 0
Turkey
State/province [38] 0 0
Edirne
Country [39] 0 0
Turkey
State/province [39] 0 0
Izmir
Country [40] 0 0
Turkey
State/province [40] 0 0
Samsun
Country [41] 0 0
United Kingdom
State/province [41] 0 0
Kent
Country [42] 0 0
United Kingdom
State/province [42] 0 0
Oxfordshire
Country [43] 0 0
United Kingdom
State/province [43] 0 0
Tyne And Wear
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Birmingham
Country [45] 0 0
United Kingdom
State/province [45] 0 0
Cardiff
Country [46] 0 0
United Kingdom
State/province [46] 0 0
Glasgow
Country [47] 0 0
United Kingdom
State/province [47] 0 0
London
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
ApcinteX Ltd
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Centessa Pharmaceuticals plc
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Centessa Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
617-468-5770
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05789524