Atenativ for Antithrombin Deficiency

Recruiting at 23 trial locations

Overseen By Sigurd Knaub, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Octapharma

Must not be taking: Warfarin, Anticoagulants, Antiplatelets

Disqualifiers: Coagulopathy, Renal insufficiency, others

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

Compensation: Varies

Number of Visits: 1

Duration: During surgery

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of Atenativ, a human plasma-derived treatment, for individuals with antithrombin deficiency undergoing heart surgery with a heart-lung machine (CPB). Researchers compare two doses of Atenativ to a placebo (a harmless, inactive substance) to determine if it improves the body's response to heparin, a common blood thinner used during surgery. This trial may suit those planning heart surgery with CPB who have previously struggled to respond to heparin. As a Phase 3 trial, it represents the final step before FDA approval, offering participants the opportunity to contribute to the potential availability of a new treatment.

Will I have to stop taking my current medications?

You may need to stop taking certain medications before participating in the trial. Specifically, you should not have taken warfarin within 3 days, direct oral anticoagulants within 2 days, ticlopidine within 14 days, prasugrel within 7 days, clopidogrel within 5 days, ticagrelor within 5 days, or glycoprotein IIb/IIIa antagonists within 1 day before the start of surgery.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that treatments using human plasma-derived antithrombin, such as Atenativ, have been tested in heart surgery patients. Although some patients have reported allergic reactions to medicines made from human blood plasma, these reactions are generally rare.

Earlier studies indicate that Atenativ is usually well-tolerated, with most patients not experiencing major side effects. This treatment often helps those who have difficulty responding to heparin, a common blood thinner. The goal is to restore normal blood clotting and reduce inflammation during surgery. Overall, Atenativ demonstrated a promising safety record in previous research. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for antithrombin deficiency?

Researchers are excited about Atenativ because it offers a unique approach to treating antithrombin deficiency. Unlike standard treatments that often rely on synthetic or recombinant methods, Atenativ is derived from human plasma, which might offer a more natural and potentially better-tolerated alternative. This treatment targets the direct increase of antithrombin levels, which is a critical component in managing blood clotting disorders. Additionally, the trial is exploring both low and high doses of Atenativ, providing insights into optimal dosing that could enhance its effectiveness compared to existing options.

What evidence suggests that this trial's treatments could be effective for antithrombin deficiency?

Research has shown that Atenativ, a treatment derived from human blood plasma, can help restore normal blood clotting in individuals with antithrombin (AT) deficiency. Antithrombin, a protein that prevents blood clots, is crucial for those who may experience clotting issues during surgeries. Studies have found that adding antithrombin concentrate can reduce inflammation and improve patient response to heparin, a blood thinner, during heart surgery. In this trial, participants will receive either a low-dose or high-dose of Atenativ, or a placebo. In a study where neither patients nor researchers knew who received the real treatment, those given Atenativ responded better to heparin than those given a placebo. This suggests Atenativ effectively helps maintain proper blood flow during surgery. ^{2 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-85 who need heart surgery with cardiopulmonary bypass and are resistant to heparin, a common blood thinner (their blood doesn't thin enough after taking it). They must be able to consent and women of childbearing age need a recent negative pregnancy test.

Inclusion Criteria

Freely given written or electronic informed consent

I am scheduled for heart surgery with a heart-lung machine.

I am a woman who can have children and have a recent negative pregnancy test.

Exclusion Criteria

I haven't taken any experimental drugs in the last 30 days.

I have taken blood thinners or clot-preventing drugs within the specified timeframes.

I have a bleeding disorder or a history of bleeding problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Atenativ or placebo to evaluate efficacy in restoring heparin responsiveness during cardiac surgery

During surgery

1 visit (in-person)

Postoperative Monitoring

Participants are monitored for changes in heparin usage, transfusion needs, and adverse events

24 hours post-surgery

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 days

What Are the Treatments Tested in This Trial?

Interventions

• Human Plasma Derived Antithrombin (Atenativ)

Trial Overview The study tests two doses of Atenativ, a drug derived from human plasma, against a placebo. The goal is to see if Atenativ can make heparin work better in patients during heart surgery that requires them to be connected to a heart-lung machine.

How Is the Trial Designed?

Group I: Low-dose Atenativ Experimental Treatment 1 Intervention

Group II: High-dose Atenativ Experimental Treatment 1 Intervention

Group III: Placebo Placebo Group 1 Intervention

Patients will receive a saline bolus dose

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

The study identified two families with type I inherited antithrombin deficiency, revealing specific gene mutations: a heterozygotic deletion (3239-3240delCT) in one proband and a nonsense mutation (3206A-->T) in another, both affecting the antithrombin gene.

Plasma levels of antithrombin antigen and activity were measured, showing reduced levels (126 mg/L and 49% for proband 1; 117 mg/L and 48% for proband 2), confirming the clinical phenotype associated with these genetic mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Two new mutations of AT gene in type I inherited antithrombin deficiency.]. Chen, Q., Lu, YL., Xu, GQ., et al.[2018]

In a Phase I clinical study, antithrombin III (ATIII) concentrate was shown to be effective in maintaining plasma ATIII levels and preventing thromboembolism in patients with congenital ATIII deficiency, with no thromboembolic events reported in 10 subjects treated prophylactically.

The treatment was well tolerated, with no evidence of infectious transmissible agents, indicating a safe option for managing both congenital and acquired ATIII deficiencies, although survival rates varied significantly based on the underlying conditions in acquired cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with antithrombin III concentrate in treatment of congenital and acquired deficiency of antithrombin. The Antithrombin III Study Group. Schwartz, RS., Bauer, KA., Rosenberg, RD., et al.[2019]

Antithrombin (AT) is crucial for regulating blood clotting, and deficiencies in AT, whether hereditary or acquired, significantly increase the risk of thromboembolism and complications during pregnancy, including fetal loss and severe preeclampsia.

Treatment for AT deficiency often involves antithrombotic therapy, and in cases of very low AT levels, patients may need higher doses of heparin or AT concentrates, which can improve blood flow to the placenta and potentially mitigate risks associated with preeclampsia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antithrombin abnormalities and perinatal management. Kobayashi, T.[2019]

Antithrombin (AT) is a crucial natural anticoagulant that not only helps prevent blood clots but also has anti-inflammatory effects, making it important for managing conditions like hereditary AT deficiency, which carries a high risk of venous thromboembolism.

Optimizing AT levels is vital during high-risk situations such as surgery and pregnancy, and there is ongoing research to identify specific patient groups that would benefit most from targeted AT therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antithrombin Therapy: Current State and Future Outlook. Rodgers, GM., Mahajerin, A.[2023]

Hereditary antithrombin (AT) deficiency is a rare genetic condition that significantly increases the risk of venous thromboembolism (VTE) by three to seven times compared to other thrombophilias, with individuals having a lifetime risk of over 50%.

While long-term anticoagulant therapy is not recommended for asymptomatic patients due to bleeding risks, short-term thromboprophylaxis is advised during high-risk situations like surgery or pregnancy, with treatment options including plasma-derived AT and human recombinant AT to maintain adequate AT levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of antithrombin concentrate in treatment of hereditary antithrombin deficiency. An update. Rodgers, GM.[2022]

Congenital antithrombin deficiency is a serious inherited condition that significantly increases the risk of thrombosis, requiring careful long-term management and anticoagulation, especially during high-risk situations like surgery and pregnancy.

Antithrombin concentrates are effective for both treating and preventing acute venous thrombosis in individuals with this deficiency, although current evidence mainly comes from retrospective studies, highlighting the need for more comprehensive research to guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of antithrombin deficiency: an update for clinicians. Bravo-Pérez, C., Vicente, V., Corral, J.[2020]

Antithrombin (AT) deficiency, which affects 1 in 500 to 1 in 5000 people, increases the risk of venous thromboembolism (VTE) and pregnancy loss, with type IIa being the most thrombophilic variant.

Diagnosis of AT deficiency requires careful testing to rule out acquired causes, and while specialized tests can help classify the type of deficiency, they are not routinely used in clinical practice despite their potential to inform treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inherited antithrombin deficiency: a review. Patnaik, MM., Moll, S.[2022]

This study involved 43 children with congenital antithrombin deficiency, revealing that 44% had experienced venous thromboembolism (VTE), with a median age of diagnosis at 12.8 years.

The research found that children with missense mutations in the SERPINC1 gene had a significantly higher 5-year VTE-free survival rate (92%) compared to those with null mutations (66.7%), highlighting the critical role of genetic testing in assessing risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of SERPINC1 mutation on thrombotic phenotype in children with congenital antithrombin deficiency-first analysis of the International Society on Thrombosis and Haemostasis pediatric antithrombin deficiency database and biorepository. Kumar, R., Bakeer, N., Dawson, J., et al.[2023]

A novel heterozygous G13328A missense mutation in the antithrombin (AT) gene was identified, leading to type I hereditary antithrombin deficiency in a family, which is linked to increased risk of thrombosis.

The mutation resulted in significantly reduced levels of antithrombin antigen and activity, with the mutant protein showing only 40% and 68% of the normal levels in cell experiments, highlighting the mutation's impact on AT function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A heterozygous point mutation G13328A in antithrombin gene causes thrombosis]. Zhou, RF., Shi, GC., Fu, QH., et al.[2006]

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. isrctn.com isrctn.com/pdf/55521313

A clinical trial looking at the effectiveness and Risk from the study drug: Some people treated with medications made from human blood plasma, such as Atenativ, have allergic or hypersensitivity ...

3. 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 ...

4. octapharma.com octapharma.com/api/download/x/5e9c90cbd7/atn-108-study-poster.pdf

A double-blind, placebo-controlled, multicentre study (ATN- ... The efficacy and safety of human plasma-derived antithrombin in heparin-resistant cardiac surgery patients: A double-blind, placebo-controlled, multicentre ...

5. clinicaltrials.eu clinicaltrials.eu/inn/human-plasma-derived-antithrombin/

Human Plasma Derived Antithrombin (Atenativ) The study aims to evaluate the effectiveness and safety of different doses of Atenativ compared to a placebo in restoring and maintaining heparin responsiveness ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06096116?cond=Antithrombin%20deficiency&rank=5

NCT06096116 | Phase 3 Study on the Efficacy and Safety ... Phase 3 Study on the Efficacy and Safety of Human Plasma Derived Antithrombin ( Atenativ ) in Heparin-Resistant Patients Scheduled to Undergo Cardiac Surgery ...