Safety, Pharmacokinetics and Efficacy of an AT-III Concentrate.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00319228
Recruitment Status : Active, not recruiting
First Posted : April 27, 2006
Last Update Posted : March 12, 2018
Information provided by (Responsible Party):
Grifols Biologicals Inc.

Brief Summary:
To assess the safety, pharmacokinetics and efficacy of a plasma-derived AT-III concentrate in the treatment of subjects with congenital AT-III deficiency.

Condition or disease Intervention/treatment Phase
Antithrombin III Deficiency Drug: Plasma-derived AT-III concentrate Phase 2 Phase 3

Detailed Description:

This study will be a prospective, unblinded, non-randomized, open-label, multi-center Phase II/III study with 2 segments, i.e. a PK evaluation (Segment I), and an assessment of prophylaxis in surgical interventions and pregnancy/delivery, (Segment II). During the PK segment, the subjects would remain on their current anticoagulation therapy except for subjects on heparin therapy where a wash-out period of at least 5 half lives would be required. In total, 15 subjects with congenital ATIII Deficiency will be enrolled for the PK assessment (Segment I).

For Segment II, fifteen episodes will be treated. Recruitment of individual subjects with high risk for venous thrombosis for Segment II of this study is necessary because of the rarity of Antithrombin deficiency in the population.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Phase II/III Pivotal Trial Evaluating the Safety, Pharmacokinetic Properties and Efficacy of a Plasma-Derived Anti-thrombin III Concentrate With Administration in Surgery, Pregnancy and Thromboembolic or Thrombotic Events.
Actual Study Start Date : January 2006
Estimated Primary Completion Date : December 2028
Estimated Study Completion Date : March 2029

Arm Intervention/treatment
Experimental: Antithrombin III Drug: Plasma-derived AT-III concentrate

Segment I: A single dose IV infusion of 50 IU/kg of ATIII-DAF/DI will be administered to each patient.

Segment II: A single dose or multiple doses depending on the subject's ATIII plasma levels and patient's specific treatment plan.

Primary Outcome Measures :
  1. The primary objectives of this clinical study are to: [ Time Frame: 2 years ]
  2. Assess the pharmacokinetic (PK) profile of AT-III in congenital AT-III deficient patients [ Time Frame: 1 year ]
  3. To measure the in vivo recovery and half-life of AT-III. [ Time Frame: 1 year ]
  4. To assess the clinical safety and tolerability of AT-III-DAF/DI. [ Time Frame: 1 year ]

Secondary Outcome Measures :
  1. To assess clinical efficacy by preventing thromboembolic or thrombotic events (prophylaxis) in individuals with congenital AT-III deficiency who are undergoing surgical procedures or who are pregnant and undergoing parturition. [ Time Frame: 1 year ]

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Congenital ATIII deficiency documented by determination of plasma levels of ATIII off all therapies. Specifically, the baseline levels of ATIII activity should be equal to or less than 60%.
  • Age > 12 years with a body weight of no less than 30 kg.
  • Have not participated in another investigational study for at least 30 days For Segment II, enrollment requires a pregnancy/delivery or a surgical procedure (it should be a major surgery although data from a minor surgery will also be collected).
  • Documented personal history of major thromboembolic or thrombotic event.
  • Male or female
  • HIV, HBV, HCV, HAV and PARVO B19 status known prior to entry.
  • The subject is willing to comply with all aspects of the protocol, including blood sampling, for the duration of the study.
  • The subject has signed an informed consent form (if at least 18 years old), or the subject's parent or legal guardian has signed the informed consent form. Subjects below the age of 18 years will also be asked to sign an assent form. All consent and assent forms must be approved in advance by the Institutional Review Board of the investigator's institution.
  • Patients with heparin-associated thrombocytopenia who require anticoagulation with non-heparin containing drugs will be eligible if they can be safely transitioned during the washout period for the Segment I PK study.
  • If pregnant, a woman must be Parvo B19 IgG antibody positive.

Exclusion Criteria:

  • Acquired deficiency of ATIII
  • Receiving concomitant treatment for thrombophilic disorders other than ATIII deficiency
  • Inability or unwillingness to comply with the protocol requirements
  • History of anaphylactic reaction(s) to blood or blood components
  • Allergies to excipients.
  • Liver function tests >/= 2.5 X ULN
  • Serum creatinine >1.2 X ULN
  • Urine >/= 2+ protein with urine dipstick test.
  • The subject is known to have abused alcohol or illicit drugs within the past 12 months.
  • The subject is unlikely to adhere to the protocol requirements of the study or is likely to be uncooperative or unable to provide a storage serum sample at the screening visit.
  • Patients on heparin-treatment who, for clinical reasons, cannot safely be discontinued from heparin therapy during the PK segment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00319228

Sponsors and Collaborators
Grifols Biologicals Inc.
Study Director: Paul J Pinciaro, PhD Grifols Biologicals Inc.

Responsible Party: Grifols Biologicals Inc. Identifier: NCT00319228     History of Changes
Other Study ID Numbers: IG-401
First Posted: April 27, 2006    Key Record Dates
Last Update Posted: March 12, 2018
Last Verified: March 2018

Keywords provided by Grifols Biologicals Inc.:
AT-III deficiency
AT-III concentrate
Bleeding disorders
Blood disorders

Additional relevant MeSH terms:
Antithrombin III Deficiency
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Blood Protein Disorders
Genetic Diseases, Inborn
Antithrombin III
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action