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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Apcintex Limited

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

16 Nov 2023 → 24 Feb 2025

Decision date (initial)

2023-08-07

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

ApcinteX Limited, a wholly owned subsidiary of Centessa Pharmaceuticals plc

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Others, Safety, Pharmacokinetic, Efficacy, Prophylaxis

To evaluate the efficacy and safety of prophylactic SerpinPC administered subcutaneously in subjects with hemophilia B (HemB) with inhibitors

Secondary objectives 2

1. To evaluate the tolerability of SerpinPC
2. To further characterize the PK profile of SerpinPC

Conditions and MedDRA coding

Hemophilia B

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Male subjects ≥12 and ≤65 years of age at the time of informed consent
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 HemB (defined as factor IX ≤0.05 IU/mL [≤5%])
4. 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
5. Historical or ongoing factor IX inhibitor requiring current treatment with bypass agents based on medical records or laboratory reports
6. 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
7. 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
8. No bleeding in the 7 days before Baseline (the prospective observation period can be extended if there is an ongoing active bleed)
9. 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
10. 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
11. 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
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 (caregiver assistance allowed for adolescents)
14. 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

Exclusion criteria 15

1. Known severe thrombophilia (defined as antithrombin deficiency and/or protein S deficiency and/or protein C deficiency)
2. Patient with previous factor IX inhibitor who responded to immune tolerance induction and remains on prophylactic factor concentrate
3. Previous deep vein thrombosis (excluding line-associated thrombosis), pulmonary embolism, myocardial infarction, or stroke
4. History of intolerance to SC injections
5. Uncontrolled hypertension (systolic blood pressure >160 mm Hg; diastolic blood pressure >100 mm Hg)
6. Weight >150 kg OR body mass index >40 kg/m2
7. Has active cancer and/or requires therapy for cancer, except for basal cell carcinoma
8. Participation in another interventional clinical trial (except for AP-0105) during the 30 days before screening
9. Ongoing, or planned treatment with gene therapy for HemB
10. 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
11. History of or other evidence of recent alcohol or drug abuse as determined by the Investigator (in the 12 months before screening)
12. 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
13. Current or planned treatment with anticoagulant or antiplatelet drugs
14. Is planning to donate/bank sperm during SerpinPC treatment AND within 30 days of last dose of SerpinPC
15. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Study Endpoint: Treated bleeds (expressed as annualized bleeding rate [ABR]) in the observation period and during the first 24 weeks under SerpinPC

Secondary endpoints 7

1. • Treated bleeds (expressed as ABR) other than those defined by the primary endpoint (eg, during the first 48 weeks)
2. • Treated spontaneous bleeds (expressed as ABR)
3. • Treated spontaneous joint bleeds (expressed as ABR)
4. • All bleeds requiring treatment (expressed as ABR; ie, all bleeds that would ordinarily be treated with factor concentrate/bypass agent if therapy were available)
5. • Total coagulation factor and/or bypass product consumption during SerpinPC treatment
6. • PK concentrations of SerpinPC throughout the study
7. • Haemophilia Quality-of-Life Questionnaire for Adults (Haem-A-QoL) Physical Health scale in subjects aged 17 to ≤65 years

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Apcintex Limited

Sponsor organisation

Apcintex Limited

Address

3rd Floor, 1 Ashley Road 1 Ashley Road

City

Altrincham

Postcode

WA14 2DT

Country

United Kingdom

Scientific contact point

Organisation

Apcintex Limited

Contact name

Chief Medical Officer

Public contact point

Organisation

Apcintex Limited

Contact name

Chief Medical Officer

Third parties 8

Locations

4 EU/EEA countries · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications