Atenativ for Antithrombin Deficiency

Recruiting at 28 trial locations

Overseen By Sigurd Knaub

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Octapharma

Must be taking: Atenativ

Must not be taking: Antithrombin concentrates

Disqualifiers: Emergency surgery, Hereditary thrombophilia, Malignancies, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1-2 weeks

38 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this study is to assess the incidence of the composite of thrombotic events (TEs) and thromboembolic events (TEEs) in patients with congenital antithrombin deficiency under when they receive Atenativ for surgical procedures or parturition.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have taken any antithrombin concentrate or antithrombin-containing blood product other than the study medication within 14 days before the study.

What data supports the effectiveness of the drug Atenativ for treating antithrombin deficiency?

AT III concentrates, like Atenativ, may be beneficial in specific situations for patients with hereditary antithrombin III deficiency, such as during delivery, acute thromboembolic complications, and postoperative care, although significant clinical benefits in reducing morbidity or mortality have not been proven in trials. ^{1 2 3 4 5}

How does the drug Atenativ differ from other treatments for antithrombin deficiency?

Atenativ is unique because it is a pasteurized concentrate of antithrombin III, obtained through a specialized process involving heparin affinity chromatography and pasteurization for viral safety. This method enhances the purity and safety of the antithrombin concentrate compared to traditional methods. ^{1 2 4 6 7}

Eligibility Criteria

This trial is for adults with congenital antithrombin deficiency who need surgery or are giving birth. It includes those aged 18-80, and a small group of minors (12-17) in the US. Pregnant women must be at least 27 weeks along. Exclusions include emergency procedures, recent surgeries, other clotting disorders, high BMI (non-pregnant), drug allergies, nursing mothers, and certain medical conditions.

Inclusion Criteria

I or my family have a history of thromboembolic events.

I am between 12 and 17 years old, living in the US, and may need treatment.

Level of antithrombin ≤60%

Exclusion Criteria

TE or TEE within the last 6 months

Body mass index >40 kg/m2 (for non-pregnant patients, only)

Known hypersensitivity or allergic reaction to antithrombin or any of the excipients in Atenativ

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intravenous infusion of Atenativ followed by maintenance doses every 24 hours for approximately 2-7 days for surgical patients and approximately 5 days for parturients

1-2 weeks

Pharmacokinetics Analysis

Assessment of pharmacokinetics parameters such as AUC, Cmax, and half-life after a single dose of Atenativ

2 weeks

Multiple visits for blood sampling

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of thrombotic and thromboembolic events

4 weeks

Treatment Details

Interventions

• Atenativ

Trial Overview The trial tests Atenativ's effectiveness in preventing blood clots during surgery or childbirth in patients with low antithrombin levels. Participants will receive Atenativ to see if it reduces the risk of thrombotic events.

Participant Groups

Group I: Atenativ treatment Experimental Treatment 1 Intervention

During the PK phase, patients will receive a 60 IU/kg Atenativ as a single intravenous infusion for PK analysis. During the treatment phase, patients will receive a single intravenous loading dose followed by maintenance doses administered every 24 hours for approximately 2-7 days for surgical patients and approximately 5 days for parturients

Who Is Running the Clinical Trial?

Octapharma

Lead Sponsor

Trials

86

Recruited

11,300+

Wolfgang Marguerre

Octapharma

Chief Executive Officer since 1983

MBA from INSEAD

Wolfgang Frenzel

Octapharma

Chief Medical Officer since 2010

MD from University of Vienna

Findings from Research

The newly developed pasteurized Antithrombin III (ATIII) concentrate shows over 99% purity and maintains approximately 95% native heparin binding, ensuring high efficacy for treating deficiencies.

The manufacturing process effectively inactivates a wide range of viruses, achieving a reduction factor of over 11.7 for HIV-1 and over 8.1 for other significant viruses, with no biochemical alterations detected in the final product, demonstrating its safety for over 32 million transfusions without seroconversion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization and viral safety validation study of a pasteurized therapeutic concentrate of antithrombin III obtained through affinity chromatography. Biescas, H., Gensana, M., Fernández, J., et al.[2007]

Antithrombin III (AT III) deficiency, which can be either qualitative or quantitative, is linked to a high risk of deep venous thrombosis and pulmonary embolisms in 40% to 70% of affected patients, particularly from puberty onward.

Diagnosis of AT III deficiency requires measuring its activity in the presence of heparin, and treatment typically involves AT III concentrated agents and heparin for severe cases, with anticoagulants like vitamin K antagonists used for preventing recurrences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hereditary deficit of antithrombin III]. Aiach, M., Fiessinger, JN., Priollet, P., et al.[2006]

Antithrombin III (AT III) concentrates effectively maintained plasma AT III levels above 100% in a patient with hereditary AT III deficiency during and after orthopedic surgery, indicating their efficacy in preventing thrombotic complications.

The study found that the half-life of AT III was shorter during surgery and early postoperative periods, suggesting increased consumption, and highlighted the importance of using biological assays over immunological assays for monitoring AT III replacement therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of congenital antithrombin III deficiency with concentrates. Mannucci, PM., Boyer, C., Wolf, M., et al.[2019]

Antithrombin III (AT III) is crucial for preventing blood clots by inhibiting key clotting factors, and its deficiency can lead to a higher risk of thromboembolic diseases, with an incidence of inherited deficiency being about 1 in 10,000.

Treatment for AT III deficiency includes administering AT III concentrates to maintain adequate levels, especially for patients undergoing major surgeries or pregnant women, while avoiding oral contraceptives due to increased thrombotic risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deficiency Of Antithrombin III (AT III) - Case Report and Review of the Literature. Găman, AM., Găman, GD.[2020]

Despite theoretical benefits and animal studies suggesting that AT III concentrates could be effective, clinical studies over 15 years have not demonstrated a significant benefit for patients, particularly in hereditary antithrombin III deficiency.

In specific clinical situations, such as during delivery or acute thromboembolic complications, AT III concentrates may provide some benefit, but there is no proven indication for their use in acquired AT III deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antithrombin III concentrates--are they clinically useful? Lechner, K., Kyrle, PA.[2007]

Antithrombin III (AT-III) deficiency, which is inherited in an autosomal dominant manner, leads to serious venous thromboembolism, especially triggered by factors like infections, trauma, and pregnancy.

Effective management of thromboembolic events in AT-III deficiency requires lifelong coumarin therapy, and during pregnancy or post-surgery, heparin must be administered alongside AT-III substitution to ensure safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antithrombin III deficiency: clinical aspects. Nagy, I.[2021]

In a study of 290 patients with deep venous thrombosis and/or pulmonary embolism, those with venous thrombosis had significantly lower levels of Antithrombin III (AT III), indicating a potential risk factor for these conditions.

Congenital AT III deficiency was identified in 13 patients from 9 families, suggesting a genetic component to their increased risk of thrombosis, particularly as many experienced their first thrombotic event before age 35.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Antithrombin III deficiency and tendency to thrombosis (author's transl)]. Lechner, K., Thaler, E., Niessner, H., et al.[2006]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Characterization and viral safety validation study of a pasteurized therapeutic concentrate of antithrombin III obtained through affinity chromatography. [2007]

2. France pubmed.ncbi.nlm.nih.gov

[Hereditary deficit of antithrombin III]. [2006]

3. England pubmed.ncbi.nlm.nih.gov

Treatment of congenital antithrombin III deficiency with concentrates. [2019]

4. Romania pubmed.ncbi.nlm.nih.gov

Deficiency Of Antithrombin III (AT III) - Case Report and Review of the Literature. [2020]

5. Germany pubmed.ncbi.nlm.nih.gov

Antithrombin III concentrates--are they clinically useful? [2007]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Antithrombin III deficiency: clinical aspects. [2021]

7. Austria pubmed.ncbi.nlm.nih.gov

[Antithrombin III deficiency and tendency to thrombosis (author's transl)]. [2006]