Atenativ for Antithrombin Deficiency

Recruiting at 33 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests Atenativ (an antithrombin III concentrate) to evaluate its effectiveness in preventing blood clots in individuals with congenital antithrombin deficiency during surgery or childbirth. Congenital antithrombin deficiency occurs when the body produces insufficient protein to prevent excessive blood clotting. The trial includes patients with this condition who are either planning surgery or are pregnant and near delivery. Participants should have a personal or family history of blood clots and must not have experienced a clot in the last six months. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially bringing a new treatment to market.

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.

Is there any evidence suggesting that Atenativ is likely to be safe for humans?

Research has shown that Atenativ, used for antithrombin deficiency, is generally well-tolerated. In one study, patients received Atenativ through an IV, and researchers reported no major safety issues. This suggests the treatment is likely safe for most people.

Since the current study is in a later phase, Atenativ has already undergone human testing. These earlier tests usually confirm that it doesn't cause serious side effects. Atenativ is also manufactured to be very pure and treated to remove viruses, reducing the risk of infections from the treatment.

Overall, while no treatment is completely without risk, Atenativ has demonstrated promise in safety across different studies. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike most treatments for antithrombin deficiency, which often involve plasma-derived or recombinant antithrombin concentrates, Atenativ is administered through a single intravenous infusion followed by maintenance doses. This method of delivery could simplify the treatment process, especially around surgical procedures or childbirth. Researchers are excited about Atenativ because it has the potential to offer rapid and sustained antithrombin supplementation, which is crucial for preventing dangerous blood clots. Additionally, its precise dosing schedule might improve patient outcomes by maintaining steady antithrombin levels during critical periods.

What evidence suggests that Atenativ might be an effective treatment for antithrombin deficiency?

Research has shown that Atenativ, a type of medicine, can assist individuals with congenital antithrombin deficiency, a condition that affects blood clotting. In this trial, participants will receive Atenativ, which aids in normal blood clotting and reduces swelling. Studies have found that Atenativ maintains normal antithrombin levels, crucial for preventing dangerous blood clots, particularly during surgeries or childbirth. Individuals with this deficiency face a higher risk of clots, and Atenativ helps manage this risk. This treatment has shown promise in addressing clotting issues related to this condition. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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) 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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06096116

NCT06096116 | Phase 3 Study on the Efficacy and Safety ... The primary objective of this study is to evaluate the efficacy of two different doses of Atenativ, versus placebo, in restoring and maintaining heparin ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10571690/

Antithrombin Therapy: Current State and Future Outlook Supplementation with AT concentrate (ATc) can help restore normal hemostasis and reduce inflammation in patients with AT deficiency in states of ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0006497121051697

Prospective, Phase III Study of the Efficacy, Safety, and ... This study will aim to evaluate the efficacy, safety, and pharmacokinetics (PK) of a high-purity, double virus inactivated, lyophilized human antithrombin III ...

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2822411

Antithrombin III Levels and Outcomes Among Patients With ... In this cohort study of patients with trauma, antithrombin III deficiency was associated with greater injury severity, increased hemorrhage, and increased ...

5. ashpublications.org ashpublications.org/blood/article-abstract/134/26/2346/422690

How I treat patients with hereditary antithrombin deficiency In this review, we will discuss cases with thrombotic manifestations and the tailored management of patients with this congenital thrombosis risk factor.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11327888/

Antithrombin III Levels and Outcomes Among Patients With ... Antithrombin III deficiency was associated with fewer ventilator-free days, hospital-free days, intensive care unit–free days and lower platelet counts.