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

Sponsor:	Grifols Biologicals Inc.
Information provided by (Responsible Party):	Grifols Biologicals Inc.
ClinicalTrials.gov Identifier:	NCT00319228

Purpose

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	Intervention	Phase
Antithrombin III Deficiency	Drug: Plasma-derived AT-III concentrate	Phase II Phase III

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: 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.

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia factor V Leiden thrombophilia hemophilia hereditary antithrombin deficiency prothrombin thrombophilia Help Me Understand Genetics

Drug Information available for: Antithrombin III

U.S. FDA Resources

Further study details as provided by Grifols Biologicals Inc.:

Primary Outcome Measures:

The primary objectives of this clinical study are to: [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Assess the pharmacokinetic (PK) profile of AT-III in congenital AT-III deficient patients [ Time Frame: 1 year ] [ Designated as safety issue: No ]
To measure the in vivo recovery and half-life of AT-III. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
To assess the clinical safety and tolerability of AT-III-DAF/DI. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	30
Study Start Date:	January 2006
Estimated Study Completion Date:	March 2018
Estimated Primary Completion Date:	December 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

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.

Eligibility

Ages Eligible for Study:	12 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00319228

Contacts

Contact: Paul J Pinciaro, PhD	410-814-7617	paul.pinciaro@grifols.com
Contact: Christine Mackay	410-814-5728	chistine.mackay@grifols.com

Locations

United States, New York
New York Presbyterian Hospital-Weill Cornell	Not yet recruiting
New York, New York, United States, 10021
Contact: Dan Matulich dam2027@med.cornell.edu
United States, Texas
University of Texas Health Science Center	Recruiting
Houston, Texas, United States, 77030-4009
Contact: Kathryn L. Moynihan 713-500-8376 kathryn.l.moynihan@uth.tmc.edu
Contact: Madeline Cantini 713-500-8377 madeline.cantini@uth.tmc.edu
United States, Virginia
University of Virginia Health System	Recruiting
Charlottesville, Virginia, United States, 22908-1370
Contact: Winsor D. Simmons, RN 434-243-0315 wds5j@virginia.edu

Sponsors and Collaborators

Grifols Biologicals Inc.

More Information

No publications provided

Responsible Party:	Grifols Biologicals Inc.
ClinicalTrials.gov Identifier:	NCT00319228 History of Changes
Other Study ID Numbers:	IG-401
Study First Received:	April 26, 2006
Last Updated:	September 6, 2011
Health Authority:	United States: Food and Drug Administration

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
Thrombophilia
Genetic Diseases, Inborn
Antithrombin III
Antithrombins

Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anticoagulants
Hematologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 09, 2012