Efficacy of Atenativ in Patients With Congenital Antithrombin Deficiency Undergoing Surgery or Delivery

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Octapharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

14 Feb 2023 → ongoing

Decision date (initial)

2024-10-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Octapharma AG

External identifiers

EU CT number

2024-515830-34-00

EudraCT number

2021-004307-40

ClinicalTrials.gov

NCT04918173

ISRCTN

ISRCTN16338908

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Efficacy, Others

The primary objective of this study is to assess the incidence of the composite of Thrombotic Events (TEs) and Thromboembolic Event (TEEs) in patients with congenital antithrombin deficiency under cover of Atenativ for surgical procedures or parturition.

Secondary objectives 3

1. Assess the single-dose pharmacokinetics (PK) of Atenativ in patients with congenital antithrombin deficiency
2. Assess coagulation parameters in patients with congenital antithrombin deficiency undergoing surgical procedures or parturition
3. Assess the safety and tolerability of Atenativ in patients with congenital antithrombin deficiency

Conditions and MedDRA coding

Congenital antithrombin deficiency

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Adult male or female patients aged ≥18 to ≤80 years for all treatment arms; Adolescent male or female patients aged ≥12 to <17 years from non-European Union countries for the PK phase (who may continue in the Treatment Phase, if applicable)
2. Documented congenital antithrombin deficiency, defined by plasma activity level of antithrombin ≤60% from medical history
3. Personal or family history of TEs or TEEs (except for PK patients)
4. For the Treatment Phase: either a) non-pregnant surgical patients scheduled for elective surgical procedure(s) known to be associated with a high risk for occurrence of TEs or TEEs, or b) pregnant patients of at least 27 weeks gestational age who are scheduled for caesarean section or delivery
5. For female patients of childbearing potential entering the PK Phase who are not known to be pregnant, and for female surgical patients of childbearing potential entering the Treatment Phase for any procedure other than caesarean section or delivery, a negative urine pregnancy test at screening and at baseline
6. Patient has provided informed consent

Exclusion criteria 15

1. Requires emergency surgery or emergency caesarean section
2. Prior diagnosis of heparin-induced thrombocytopenia
3. TE or TEE within the last 6 months
4. Female patients who are nursing at the time of screening1 1not applicable for female patients who plan to breastfeed after giving birth
5. Have participated in another investigational study within the last 30 days
6. Has undergone surgery within the last 6 weeks
7. History or suspicion of another hereditary thrombophilic disorder other than antithrombin deficiency (e.g., activated protein C [APC] resistance/Factor V Leiden, Protein S or C deficiency, prothrombin gene mutation [G20210A], or acquired [lupus anticoagulant] thrombophilic disorder)
8. Malignancies, renal failure (patients on renal replacement therapy), or severe liver disease (aspartate aminotransferase [ASAT] >5 times the upper limit of normal)
9. Body mass index >40 kg/m2 (for non-pregnant patients, only)
10. Known hypersensitivity or allergic reaction to antithrombin or any of the excipients in Atenativ
11. History of anaphylactic reaction(s) to blood or blood components
12. Refusal to receive transfusion of blood-derived products
13. Administration of any antithrombin concentrate or antithrombin-containing blood product within 14 days of either of the two phases of the study
14. Persons dependent on the sponsor, the investigator or the centre of investigation
15. Persons placed in an institution by administrative or judicial order

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence of the composite of TEs and TEEs in patients with congenital antithrombin deficiency under cover of Atenativ for surgical procedures or parturition to 30 days post treatment initiation.

Secondary endpoints 3

1. • PK parameters: o Area under the curve (AUCnorm(0–∞)) o Maximum plasma concentration (Cmax) o Half-life (t1/2) o Mean residence time (MRT) o Clearance (CL) o Incremental in vivo recovery (IVR; peak concentration of antithrombin observed within the first hour after infusion) o Volume of distribution at steady state (Vss) o Time to reach Maximum Plasma Concentration (Tmax)
2. • Efficacy Parameters: o Antithrombin activity; o Coagulation parameters (activated partial thromboplastin time [aPTT], prothrombin time [PT], international normalised ratio [INR] and fibrinogen)
3. • Safety Parameters: o Adverse events (AEs) and serious AEs (SAEs); o Length of hospital stay; o Vital signs (including systolic and diastolic blood pressure, pulse rate, body temperature, respiration rate, results of physical examination); o Standard haematological and clinical chemistry safety variables, as well as thrombogenicity markers including D-dimer, prothrombin fragment 1 + 2 (F1+2)*, and thrombin-antithrombin complex (TAT)* * if available from local laboratories

Investigational products

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

Test 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Octapharma AG

Sponsor organisation

Octapharma AG

Address

Seidenstrasse 2

City

Lachen SZ

Postcode

8853

Country

Switzerland

Scientific contact point

Organisation

Octapharma AG

Contact name

Vice President CR&D Haematology

Public contact point

Organisation

Octapharma AG

Contact name

Vice President CR&D Haematology

Third parties 3

Locations

8 EU/EEA countries · 19 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

Documents 93 files

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

Application history

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