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 (PRESent-2)

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

13 Nov 2023 → 28 Feb 2025

Decision date (initial)

2023-07-26

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

To evaluate the efficacy and safety of prophylactic SerpinPC administered subcutaneously (SC) in subjects with moderately severe to severe hemophilia B (HemB)

Secondary objectives 3

1. To evaluate the tolerability of SerpinPC
2. To evaluate the efficacy and safety of prophylactic SerpinPC in subjects with hemophilia
3. To further characterize the PK profile of SerpinPC

Conditions and MedDRA coding

Severe Hemophilia A or Moderately Severe to Severe Hemophilia B

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Male subjects ≥12 and ≤65 years of age with severe HemA, with or without inhibitors, or moderately severe to severe HemB, without high titer inhibitor (high titer inhibitor defined as ≥5 Bethesda Units [BU]/mL) and not requiring current treatment with bypass agents.
2. Subject is currently included in a prophylaxis program OR subject is undergoing an on-demand treatment regimen; if the latter, must have had ≥6 documented acute bleeding episodes that required treatment during the 6 months before Screening
3. At least 12 (Part 1) or 24 (Part 2) weeks of prospective documentation of bleeding episodes in the AP-0105 noninterventional study before dosing, or willing to complete the observation period in AP-0102
4. No bleeding in the 7 days before Baseline (observation period can be extended if actively bleeding)
5. Adequate hematologic, hepatic, and renal function, and D-dimer of ≤750 μg/L

Exclusion criteria 4

1. Known severe thrombophilia, previous deep vein thrombosis (excluding line-associated thrombosis), pulmonary embolism, myocardial infarction, stroke, uncontrolled hypertension (>160/100 mmHg) or has active cancer and/or requires therapy for cancer, except for basal cell carcinoma
2. Subject with previous factor VIII or factor IX inhibitor who responded to immune tolerance induction and remains on prophylactic factor concentrate
3. Body weight < 30 kg OR >150 kg OR body mass index >40 kg/m2
4. Use of emicizumab in the 24 weeks before Baseline (Day 0) / Ongoing, or planned treatment with gene therapy for hemophilia / Current or planned treatment with anticoagulant or antiplatelet drugs

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 under SerpinPC at the end of Part 2 Week 24 in subjects with HemB previously receiving “on-demand” treatment

Secondary endpoints 7

1. Treated bleeds (expressed as ABR) other than those defined by the primary endpoint (eg, bleeds during the first 48 weeks, and in those subjects receiving prior “prophylaxis” treatment)
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 treated bleeds and 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
6. PK concentrations of SerpinPC throughout the study
7. Haemophilia-specific QoL Instrument for Adults (Haem-A-QoL) Physical Health scale in subjects aged 17 to ≤65 years with hemophilia and the end of Part 3 Week 24).

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

7 EU/EEA countries · 24 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 26 files

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

Application history

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